Cancers

18 pages, 1160 KB

Open AccessReview

Integrating Artificial Intelligence into Breast Cancer Histopathology: Toward Improved Diagnosis and Prognosis

by Gavino Faa, Eleonora Lai, Flaviana Cau, Ferdinando Coghe, Massimo Rugge, Jasjit S. Suri, Claudia Codipietro, Benedetta Congiu, Simona Graziano, Ekta Tiwari, Andrea Pretta, Pina Ziranu, Mario Scartozzi and Matteo Fraschini

Cancers 2026, 18(7), 1184; https://doi.org/10.3390/cancers18071184 - 7 Apr 2026

Cited by 2 | Viewed by 1431

Abstract

Histopathological evaluation of tissue sections remains the gold standard for the diagnosis, classification, and grading of breast cancer (BC). The widespread adoption of whole-slide imaging (WSI) has enabled the digitization of histological slides and facilitated the development of artificial intelligence (AI) approaches for [...] Read more.

Histopathological evaluation of tissue sections remains the gold standard for the diagnosis, classification, and grading of breast cancer (BC). The widespread adoption of whole-slide imaging (WSI) has enabled the digitization of histological slides and facilitated the development of artificial intelligence (AI) approaches for computational pathology. In recent years, machine learning and deep learning (DL) algorithms have been increasingly investigated for the analysis of hematoxylin and eosin (H&E)-stained images, with potential applications in tumor detection, histological classification, prognostic stratification, and prediction of treatment response. This narrative review summarizes recent developments in AI-driven models applied to BC histopathology and discusses their potential role in supporting diagnostic and prognostic assessment. Several studies have demonstrated the promising performance of DL algorithms in tasks such as the detection of lymph node metastases, assessment of residual tumor after neoadjuvant therapy, and prediction of clinical outcomes from histopathological images. Emerging research has also explored the possibility of inferring molecular and biomarker information from histology images, although these approaches currently identify statistical associations rather than direct molecular measurements. Despite the rapid expansion of this research field, significant barriers remain before routine clinical implementation can be achieved. Key challenges include dataset bias, variability in staining and image acquisition, limited external validation across institutions, and the need for transparent and reproducible model development. In addition, the translation of AI-based systems into clinical practice requires compliance with regulatory frameworks governing software used for medical purposes, such as those established by the U.S. Food and Drug Administration. Overall, AI represents a promising research direction in computational pathology and may contribute to decision-support tools capable of assisting pathologists in the analysis of digital slides. Continued efforts toward methodological rigor, large multicenter datasets, and prospective validation studies will be essential to determine the future role of AI in BC histopathology. Full article

(This article belongs to the Collection Artificial Intelligence in Oncology)

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14 pages, 436 KB

Open AccessArticle

Long-Term Young Adult Cancer Survivors with Ovarian Cancer: Subgroup Analysis of the Study “Expression VI–Carolin Meets HANNA–Holistic Analysis of Long-Term Survival with Ovarian Cancer”: The International NOGGO, ENGOT, and GCIG Survey

by Desislava Dimitrova, Eleftherios Pierre Samartzis, Dario Zocholl, Maria-Pilar Barretina-Ginesta, Katharina Leitner, Pavel Havelka, Patriciu Achimas-Cadariu, Cagatay Taskiran, Suzana Mittelstadt, Els Van Nieuwenhuysen, Gerd Bauerschmitz, Viola Heinzelmann-Schwarz, Ainhoa Madariaga, Uta Ringsdorf, Tibor Zwimpfer, Caterina Madroñal, Hans-Martin Enzinger, Sara Al Rubaish, Jalid Sehouli and Hannah Woopen

Cancers 2026, 18(7), 1183; https://doi.org/10.3390/cancers18071183 - 7 Apr 2026

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Abstract

Background/Objectives: Ovarian cancer is typically diagnosed in postmenopausal women, so there are limited data available for young adult cancer survivors (YACS). The aim was to assess the patient perspective of YACS. Methods: In this international and multicenter cross-sectional survey study, patient history, long-term [...] Read more.

Background/Objectives: Ovarian cancer is typically diagnosed in postmenopausal women, so there are limited data available for young adult cancer survivors (YACS). The aim was to assess the patient perspective of YACS. Methods: In this international and multicenter cross-sectional survey study, patient history, long-term side effects, and patient perspective were assessed. Long-term survival was defined as survival of at least five years after cancer diagnosis. Two groups were defined: (1) 18–40 years and (2) ≥41 years. Results: Altogether, 1833 long-term survivors (LTS) have been recruited, with 1771 patients ≥41 years and 62 patients 18–40 years at recruitment. FIGO stages were similar; among the patients, 99.0% had received primary surgery followed by chemotherapy in 90.3%. Almost 50% still experienced long-term side effects. Patients ≤ 40 years reported more frequently not only gastrointestinal symptoms such as nausea/vomiting (44.4%, p = 0.01), bloating (59.3%, p = 0.038), and constipation (60%, p = 0.015) but also depression (31.4%, p = 0.02), lymphedema (45.3%, p = 0.026), and concentration difficulties (30.6%, p = 0.002). Distress levels were also higher in YACS, especially concerning insurance/finances, work/school, child care, worries, and sadness. Polyneuropathy and secondary cancer were the only side effects that were more frequent in the elder cohort (polyneuropathy: 20.3% vs. 4.3%, p = 0.002, and secondary cancer: 8.4% vs. 0%, p = 0.014). YACS were more physically active (p = 0.003) and interested in studies about long-term cancer survivorship in 87.2%. Conclusions: Long-term side effects are equally common in YACS after ovarian cancer, but with a focus on practical problems, mental health, gastrointestinal problems, and sexuality. This knowledge should be incorporated into follow-up care of ovarian cancer patients in order to improve quality of life. Full article

(This article belongs to the Special Issue Survivorship Following Childhood, Adolescent, and Young Adult Cancer)

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38 pages, 592 KB

Open AccessSystematic Review

Supramaximal Resection in Glioblastoma: Expanding Surgical Boundaries in the Era of Precision Neuro-Oncology—A Systematic Review

by Stuart D. Harper, Travis Perryman, Brandon Carlson-Clarke, Shivani Baisiwala, Brandon Rogowski, Amani Carson, Isha Sharma, Shail G. Patel, Eliana S. Oduro, Alondra Delgadillo, Nishvith Sudhakar, Mahmoud I. Youssef and Kunal S. Patel

Cancers 2026, 18(7), 1182; https://doi.org/10.3390/cancers18071182 - 7 Apr 2026

Viewed by 1662

Abstract

Background: Glioblastoma remains the most aggressive and treatment-resistant primary brain tumor, with patient outcomes strongly associated with the extent of surgical resection. Tumor recurrence is largely driven by infiltrating glioma cells that extend beyond the contrast-enhancing margin, which has traditionally served as the [...] Read more.

Background: Glioblastoma remains the most aggressive and treatment-resistant primary brain tumor, with patient outcomes strongly associated with the extent of surgical resection. Tumor recurrence is largely driven by infiltrating glioma cells that extend beyond the contrast-enhancing margin, which has traditionally served as the boundary for surgical resection. Advances in pre- and intraoperative imaging, functional mapping, and fluorescence guidance have challenged the conventional definition of “maximal safe resection” and given rise to the concept of supramaximal resection (SMR). This technique, where surgical resection extends beyond the contrast-enhancing border, has garnered significant interest in recent years and shown promising preliminary survival outcomes. However, the lack of standardized definitions and methodological consistency has limited reproducibility and clinical adoption. Methods: A systematic literature search of PubMed/MEDLINE, Embase, and Web of Science was performed from database inception through March 2026 in accordance with PRISMA guidelines. Studies investigating resection beyond the contrast-enhancing tumor margin in adult glioblastoma patients were evaluated for inclusion. Results: A total of 1045 records were identified, with 37 studies meeting inclusion criteria. Across studies, SMR was frequently associated with improved progression-free and overall survival in selected patients, particularly following complete contrast-enhancing tumor resection. However, substantial heterogeneity exists in SMR definitions, and the current body of evidence is largely retrospective and derived from high-volume centers. Conclusions: SMR represents a promising extension of maximal safe resection targeting infiltrative tumor beyond conventional imaging boundaries. While emerging evidence suggests survival benefits, variability in methodology and patient-specific factors require cautious interpretation. Future standardization and prospective validation are needed to better define the role of SMR within multimodal glioblastoma treatment. Full article

(This article belongs to the Special Issue Modern Neurosurgical Management of Gliomas)

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16 pages, 1285 KB

Open AccessArticle

Predictive Nomogram for Recurrence After Upfront Surgery for Resectable Pancreatic Ductal Adenocarcinoma: A Multicenter Study (OS-HBP-2)

by Ryuichi Yoshida, Kosei Takagi, Kazuya Yasui, Masayoshi Hioki, Takehiro Okabayashi, Toru Kojima, Yoshikatsu Endo, Daisuke Nobuoka, Kenta Sui, Masaru Inagaki, Susumu Shinoura, Masashi Kimura, Tatsuo Matsuda, Hideki Aoki and Toshiyoshi Fujiwara

Cancers 2026, 18(7), 1181; https://doi.org/10.3390/cancers18071181 - 7 Apr 2026

Cited by 1 | Viewed by 975

Abstract

Background/Objectives: Postoperative recurrence is a critical issue in the treatment of resectable pancreatic ductal adenocarcinoma (rPDAC). Moreover, the prognosis after early recurrence is extremely poor. This study aimed to develop a recurrence prediction model and to define early recurrence after upfront surgery [...] Read more.

Background/Objectives: Postoperative recurrence is a critical issue in the treatment of resectable pancreatic ductal adenocarcinoma (rPDAC). Moreover, the prognosis after early recurrence is extremely poor. This study aimed to develop a recurrence prediction model and to define early recurrence after upfront surgery (UFS) for rPDAC. Methods: This multicenter retrospective study included patients who underwent UFS for anatomically rPDAC between January 2013 and December 2017. Multivariate analyses were conducted to identify the risk factors for recurrence-free survival and to construct a recurrence prediction model. Subsequently, a minimum p value approach was used to determine the optimal cutoff values for early and late recurrence. Results: The cohort included 603 patients (325 men and 278 women). During the median follow-up period of 25 months (interquartile range, 15–38 months), 381 patients (63.2%) experienced a recurrence. Multivariate analyses revealed carbohydrate antigen 19-9 ≥37 U/mL (hazard ratio [HR], 1.58; p < 0.001), tumor size ≥ 2.2 cm (HR, 1.59; p < 0.001), lymph node metastasis (HR, 1.86; p < 0.001), R1 resection (HR, 1.56; p = 0.002), and no adjuvant chemotherapy (HR, 1.54; p < 0.001) as independent predictors. The recurrence prediction model demonstrated an area under the curve of 0.72–0.75. The optimal threshold for early and late recurrences was a recurrence-free interval of five months. Carbohydrate antigen 19-9 ≥ 156 U/mL was a significant predictor of early recurrence (OR, 3.28; p < 0.001). Conclusions: This study identified the prognostic risk factors for recurrence and developed a recurrence prediction model for patients undergoing UFS for rPDAC. Moreover, a recurrence-free interval of five months was identified as the optimal threshold for distinguishing between early and late recurrences. Full article

(This article belongs to the Section Clinical Research in Cancer)

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20 pages, 2032 KB

Open AccessArticle

Immunohistochemical Expression of IDO and PD-L1 in Distinct Compartments of Breast Cancer Tissue: Correlation with Clinicopathological Features and Outcomes

by Nikolaos Syrigos, Alexandros Mougiakos, Anastasia Konstantinidou, Emmanouil Panagiotou, Anastasia Karachaliou, Eleni Fyta, Ioannis Vamvakaris, Evangelia Karagianni, Elias Kotteas, Sophocles Lanitis, Christos Markopoulos, Theodoros Troupis and Dimitra Grapsa

Cancers 2026, 18(7), 1180; https://doi.org/10.3390/cancers18071180 - 7 Apr 2026

Viewed by 848

Abstract

Background: Indoleamine 2,3-dioxygenase (IDO) is an immune checkpoint that has been shown to play a key immunomodulatory role in various solid tumors, including breast cancer (BC). Although increased IDO expression has been previously observed in some BC subtypes, mainly triple-negative BC (TNBC), [...] Read more.

Background: Indoleamine 2,3-dioxygenase (IDO) is an immune checkpoint that has been shown to play a key immunomodulatory role in various solid tumors, including breast cancer (BC). Although increased IDO expression has been previously observed in some BC subtypes, mainly triple-negative BC (TNBC), the clinical relevance of this protein across the entire range of BC and its exact correlations with other immune checkpoints remain to be elucidated. We herein aimed to further investigate the differential expression patterns of IDO and programmed death-ligand 1 (PD-L1) in variable BC subtypes and in distinct compartments of breast cancer tissue, and to explore their potential associations with standard patient- and tumor-related clinicopathological parameters as well as prognosis. Methods: This was a retrospective multi-center cohort study of 150 female patients with BC. The clinicopathological parameters analyzed were retrieved from the medical records of patients while sections from archival formalin-fixed, paraffin-embedded (FFPE) tissue blocks were also obtained for the performance of immunohistochemistry. The expression of IDO and PD-L1 was evaluated separately on tumor cells (IDO/CA, PD-L1/CA), lymphocytes (IDO/L, PD-L1/L) and stromal cells (IDO/S, PD-L1/S) and the results were correlated with the remaining clinical and pathological features of patients, as well as with local recurrence, metastasis and survival. Results: The mean age of patients was 59.5 years (SD = 13.4 years). Positive expression of IDO/CA, IDO/L and IDO/S was found in 6%, 93.3% and 90.7% of tissue samples, respectively, while 4%, 11.2% and 6.7% of tumors were positive for PD-L1/CA, PD-L1/L and PD-L1/S, respectively. A significantly higher rate of positive IDO/CA expression was observed in triple-negative BC (TNBC) patients (p = 0.037). Positive expression of IDO-CA was also significantly associated with positivity for PD-L1/L and PD-L1/S (p = 0.001 and p = 0.015, respectively). Multivariable logistic regression analysis showed independent correlations between IDO/CA and IDO/L and the presence of invasive ductal carcinoma (IDC) (OR = 1.10; p = 0.026) and N1 status (OR = 10.93; p = 0.039), respectively, IDO/S and both N1 (OR = 14.64; p = 0.018) and positive HER2 status (OR = 6.11; p = 0.019), PD-L1/L and high Ki67 (OR = 7.96; p = 0.001) as well as negative ER (OR = 0.08; 0.003) and PR status (OR = 0.09; p = 0.002), PD-L1/S and both NST (no special type) histology (OR = 4.68; p = 0.032) and negative ER status (OR = 0.21; p = 0.044). No statistically significant associations were observed between the expression patterns of the examined biomarkers and recurrence, metastasis or survival. Conclusions: In our study, IDO expression on tumor cells was predominantly observed in TNBC and was found to correlate with PD-L1 expression in the lymphocytic and stromal compartments. Furthermore, expression of PD-L1 among lymphocytes was found to independently correlate with unfavorable clinicopathological parameters, including high proliferation rate and negative hormone receptor status. Full article

(This article belongs to the Special Issue Immune Biomarkers in Solid Tumors: From Peripheral Blood Parameters to Tissue-Based Indicators for Prognosis and Therapy Response)

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16 pages, 1979 KB

Open AccessEditor’s ChoiceReview

Triple-Negative Breast Cancer Brain Metastasis: A Comprehensive Review of Epidemiology, Molecular Pathobiology, and Therapeutic Frontiers

by Hongli Yang, Yang Zhao, Yue Wang, Xiaoyuan Ma, Jinmei Ling, Xianyi Zeng, Zihuang Li and Guixiang Liao

Cancers 2026, 18(7), 1179; https://doi.org/10.3390/cancers18071179 - 7 Apr 2026

Cited by 2 | Viewed by 1810

Abstract

Triple-negative breast cancer (TNBC) is associated with a high risk of brain metastases (BMs). Although systemic therapies have improved extracranial disease control, the central nervous system (CNS) remains less accessible to numerous agents. As a result, this limited drug penetration makes brain metastases [...] Read more.

Triple-negative breast cancer (TNBC) is associated with a high risk of brain metastases (BMs). Although systemic therapies have improved extracranial disease control, the central nervous system (CNS) remains less accessible to numerous agents. As a result, this limited drug penetration makes brain metastases (BMs) remain common in TNBC, which are a leading cause of serious symptoms. This review summarizes recent key advances in triple-negative breast cancer brain metastases (TNBC-BMs), including epidemiology, prognostic stratification, biological mechanisms of CNS tropism and treatment resistance, and evolving management strategies. We discuss potential mechanisms of brain colonization, including the FOXC1-CXCR4 axis, ST6GALNAC5-related interactions with the blood–brain barrier (BBB), and the bidirectional crosstalk between metastatic cells and the brain microenvironment, particularly astrocytes and microglia. Furthermore, we evaluate the evolving clinical management, emphasizing the transition from whole-brain radiotherapy (WBRT) toward more selective local approaches such as stereotactic radiotherapy (SRS) and hippocampal sparing techniques. Concurrently, we examine the integration of CNS active systemic therapy across specific molecular subsets. This review systematically distinguishes standard-of-care interventions from investigational strategies, ultimately underscoring critical evidence gaps within the TNBC-BM landscape. Full article

(This article belongs to the Special Issue Advances in the Management and Prognosis of Brain Metastases)

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9 pages, 227 KB

Open AccessArticle

Functional Outcomes and Recurrence After Arthroscopy-Based Treatment of Pigmented Villonodular Synovitis of the Knee: A 20-Year Single-Center Series

by Efstathios Konstantinou, Alexandros Koskiniotis, Antonios Koutalos, Konstantinos Malizos, Theofilos Karachalios and Michael Hantes

Cancers 2026, 18(7), 1178; https://doi.org/10.3390/cancers18071178 - 7 Apr 2026

Viewed by 879

Abstract

Background/Objectives: Tenosynovial giant cell tumor (TGCT), historically referred to as pigmented villonodular synovitis (PVNS), is a rare proliferative synovial disorder that most commonly affects the knee and may lead to progressive joint damage. Surgical synovectomy remains the mainstay of treatment, although recurrence [...] Read more.

Background/Objectives: Tenosynovial giant cell tumor (TGCT), historically referred to as pigmented villonodular synovitis (PVNS), is a rare proliferative synovial disorder that most commonly affects the knee and may lead to progressive joint damage. Surgical synovectomy remains the mainstay of treatment, although recurrence remains a concern, particularly in diffuse disease. The purpose of this study was to evaluate functional outcomes and recurrence following arthroscopic synovectomy with selective open excision for TGCT of the knee. Methods: This retrospective case series included patients treated surgically for TGCT of the knee at a single tertiary orthopaedic center between 2003 and 2023. The extended study period may have introduced variability in surgical technique and perioperative management due to evolving clinical practice. All patients underwent arthroscopic synovectomy, with open excision performed when necessary to address posterior or extra-articular disease not amenable to complete arthroscopic resection. Functional outcomes and knee range of motion were evaluated preoperatively and at final follow-up. Recurrence and complications were recorded. Results: A total of 43 patients were included with a mean follow-up of 8.1 years. Diffuse TGCT was present in 32 patients (74%), while 11 patients (26%) had localized disease. Arthroscopic synovectomy was performed in all cases, with additional open excision required in 10 patients. Functional scores and range of motion improved significantly at final follow-up (p < 0.001). Disease recurrence occurred in 8 patients (18.6%), all with diffuse disease, and was treated with revision arthroscopic synovectomy. Conclusions: Arthroscopic synovectomy with selective open excision when required was associated with significant improvement in functional outcomes and knee range of motion. Disease recurrence occurred in 18.6% of patients and exclusively in those with diffuse disease, emphasizing the need for careful postoperative surveillance. Full article

(This article belongs to the Special Issue Sarcoma Management in Orthopaedic Oncology)

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15 pages, 1358 KB

Open AccessArticle

Comparison of Comprehensive Serum miRNA Sequencing and Apolipoprotein A2 Isoforms for Early Detection of Pancreatic Cancer

by Hirotaka Kashima, Munenori Kawai, Kei Iimori, Munemasa Nagao, Takamitsu J. Morikawa, Ryo Otomo, Mitsuharu Hirai, Kosuke Minaga, Masanori Asada, Atsushi Umemura, Yoshito Uenoyama, Toshihiro Morita, Shujiro Yazumi, Ryuki Minami, Saiko Marui, Yuki Yamauchi, Yoshitaka Nakai, Yutaka Takada, Seiji Shio, Takuto Yoshioka, Naoki Kanda, Tomonori Masuda, Kazuyuki Nagai, Etsuro Hatano, Akihisa Fukuda and Hiroshi Seno Show full author list Hide full author list

Cancers 2026, 18(7), 1177; https://doi.org/10.3390/cancers18071177 - 7 Apr 2026

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Abstract

Backgrounds and Aim: Pancreatic cancer is frequently diagnosed at advanced stages, highlighting the need for biomarkers that are capable of detecting early-stage disease in asymptomatic individuals. Recently, apolipoprotein A2 isoforms (ApoA2-ATQ/AT) have been reported as a new blood biomarker for pancreatic cancer. We [...] Read more.

Backgrounds and Aim: Pancreatic cancer is frequently diagnosed at advanced stages, highlighting the need for biomarkers that are capable of detecting early-stage disease in asymptomatic individuals. Recently, apolipoprotein A2 isoforms (ApoA2-ATQ/AT) have been reported as a new blood biomarker for pancreatic cancer. We recently developed diagnostic models based on 100 highly expressed serum microRNAs (miRNAs) combined with CA19-9; these models achieved high accuracy in terms of distinguishing individuals with pancreatic cancer from healthy individuals. This study aimed to compare the diagnostic performance of these miRNA-based models with that of the ApoA2-ATQ/AT biomarker. Methods: Comprehensive sequencing of serum miRNAs was conducted using samples from 120 pancreatic cancer patients recruited across 14 hospitals, along with 93 healthy controls without cancer. Serum CA19-9 levels, miRNA index values, miRNA+CA19-9 index values, and ApoA2 index values were assessed. miRNA-based indices were derived from classification models built on an automated machine-learning platform. Results: The miRNA model (AUC 0.94; 95% CI 0.91–0.97) and the miRNA+CA19-9 model (AUC 0.99; 95% CI 0.98–1.00) outperformed ApoA2 (AUC 0.89; 95% CI 0.84–0.93) in terms of distinguishing individuals with pancreatic cancer from healthy controls across all stages. In early-stage disease (stages 0–I and 0–II), both miRNA-based models also demonstrated superior performance. Strong negative correlations were observed between the ApoA2 index and both the miRNA model index (r = −0.62) and the miRNA+CA19-9 index (r = −0.63). Conclusions: These findings suggest that miRNA-based diagnostic models, particularly when combined with CA19-9, could serve as powerful tools for the early detection of pancreatic cancer. Full article

(This article belongs to the Special Issue Novel Diagnosis and Treatment Approaches in Pancreatic Cancer)

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22 pages, 1912 KB

Open AccessArticle

ANGPTL3, Apo CIII, Leptin and Triglycerides Are Elevated in Metastatic Prostate Cancer

by Gabriel Boulay, Marwan Khodr, Ann-Charlotte Bergeron, Émilie Wong Chong, France-Hélène Joncas, Chloé Castonguay, Karine Robitaille, Hélène Hovington, Vincent Fradet, Alain Bergeron, Frédéric Pouliot, Jonatan Blais, Nabil G. Seidah, Frédéric Calon and Anne Gangloff

Cancers 2026, 18(7), 1176; https://doi.org/10.3390/cancers18071176 - 7 Apr 2026

Cited by 1 | Viewed by 1162

Abstract

Background/Objectives: Prostate cancer (PCa) cells are known to heavily depend on lipids to support their growth. We hypothesized that hyperlipidemic factors, for which inhibitors are already available and used to treat cardiovascular disease, would be dysregulated in metastatic PCa (mPCa). The goal of [...] Read more.

Background/Objectives: Prostate cancer (PCa) cells are known to heavily depend on lipids to support their growth. We hypothesized that hyperlipidemic factors, for which inhibitors are already available and used to treat cardiovascular disease, would be dysregulated in metastatic PCa (mPCa). The goal of this case-control study, including 35 men per group, was to compare the levels of PCSK9, ANGPTL3, Apo CIII, leptin, and the lipid profile in patients with mPCa versus localized Gleason 8/9 PCa (lPCa) and patients at risk of developing PCa (controls). Methods: Protein levels were assessed using ELISAs, while lipids were measured using the Roche Cobas analytical platform. Results: The following circulating analytes were higher in mPCa: triglycerides (in mmol/L; controls 1.7 ± 1.2, lPCa 1.5 ± 0.7, mPCa 2.3 ± 1.2, p = 0.0004), Apo CIII (in µg/mL; control 110.7 ± 55.7, lPCa 115.0 ± 57.64, mPCa 159.9 ± 96.7, p = 0.0179), ANGPTL3 (in ng/mL; controls 41.7 ± 20.0, lPCa 42.8 ± 24.1, mPCa 57.3 ± 26.9, p = 0.0390), and leptin (in ng/mL, controls 9.6 ± 9.1, lPCa 8.2 ± 7.9, mPCa 17.7 ± 17.8, p < 0.0001). Surprisingly, PCSK9 levels were negatively correlated with LDL in the entire cohort. Conclusions: In this cohort of men, whole-body lipid metabolic rewiring is a feature restricted to the metastatic phase of prostate cancer, suggesting it may play a significant role in the progression toward more aggressive cancer forms. Given the availability of drugs targeting ANGPTL3 and Apo CIII, the therapeutic potential of these drugs should be evaluated in metastatic PCa. Full article

(This article belongs to the Section Tumor Microenvironment)

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21 pages, 1344 KB

Open AccessReview

Reframing RB Tumor Suppressor Dysfunction as a Therapeutic Vulnerability in Cancer

by Rada Malko, Harlan E. Shannon, Erika A. Dobrota, Keiko E. Kreklau, Lauren K. Stevens, Kyle W. Jackson, M. Reza Saadatzadeh, Pankita H. Pandya and Karen E. Pollok

Cancers 2026, 18(7), 1175; https://doi.org/10.3390/cancers18071175 - 7 Apr 2026

Viewed by 998

Abstract

The retinoblastoma (RB) protein was the first tumor suppressor discovered and has been extensively studied for its canonical role in cell-cycle regulation. However, RB has broader noncanonical roles in DNA damage repair, chromosomal stability, apoptosis control, lineage commitment, cell differentiation and broad transcriptional [...] Read more.

The retinoblastoma (RB) protein was the first tumor suppressor discovered and has been extensively studied for its canonical role in cell-cycle regulation. However, RB has broader noncanonical roles in DNA damage repair, chromosomal stability, apoptosis control, lineage commitment, cell differentiation and broad transcriptional regulation. Historically, RB inactivation has been associated with tumorigenesis, as well as resistance to cyclin-dependent kinase 4/6 inhibitors (CDK4/6i), leading to its investigation as a potential predictive biomarker. However, clinical data have not demonstrated that RB function reliably predicts response to CDK4/6i consistently. These discrepancies highlight the need to reconsider RB’s role in therapeutic response, as RB loss can promote replication stress, induce chromosomal instability, and lead to transcriptional reprograming, potentially generating context-specific therapeutic vulnerabilities. In this review, we examine the multifaceted biology of RB and evaluate how its loss influences responses to chemotherapy and targeted therapies. We highlight emerging strategies that exploit RB-deficient states using rational monotherapy and combination approaches. Reframing RB dysfunction from a binary biomarker to a driver of exploitable cellular vulnerabilities may inform and expand precision oncology strategies for aggressive and treatment-resistant cancers. Full article

(This article belongs to the Special Issue Cancer Cell Vulnerabilities on Pathways Regulating the Cell Cycle)

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9 pages, 427 KB

Open AccessArticle

Clinical Impact of Nivolumab in Sinonasal Mucosal Melanoma: A 14-Year Single-Center Retrospective Study and Comprehensive Literature Review

by Kosuke Terazawa, Ryo Utakata, Ryota Iinuma, Masashi Kuroki, Tatsuhiko Yamada, Hiromasa Ishihara, Ryo Kawaura, Hiroshi Okuda, Kenichi Mori, Hirofumi Shibata, Natsuko Obara, Miki Umeda, Ryoukichi Ikeda, Ken Saijo and Takenori Ogawa

Cancers 2026, 18(7), 1174; https://doi.org/10.3390/cancers18071174 - 6 Apr 2026

Viewed by 946

Abstract

Background: Sinonasal mucosal melanoma (SNMM) is a rare aggressive malignancy often resected with postoperative irradiation, with some evidence supporting the use of immune checkpoint inhibitors (ICIs). This study explores the potential efficacy and safety of nivolumab in 16 patients with SNMM, and [...] Read more.

Background: Sinonasal mucosal melanoma (SNMM) is a rare aggressive malignancy often resected with postoperative irradiation, with some evidence supporting the use of immune checkpoint inhibitors (ICIs). This study explores the potential efficacy and safety of nivolumab in 16 patients with SNMM, and reviews the literature of ICI use in it. Methods: We retrospectively analyzed 16 patients who had pathologically confirmed SNMM treated at Gifu University Hospital over a 14-year period between 2010 and 2024, of whom 11 received nivolumab. Clinical characteristics, treatment modalities, immune-related adverse events (irAEs), progression-free survival (PFS), and overall survival (OS) were examined. Kaplan–Meier and log-rank tests were used for survival analysis. A comprehensive literature review was done regarding ICI in SNMM. Results: Among the 16 patients, 11 received nivolumab and five did not. The nivolumab group showed longer median survival (median OS 26 mo vs. 8 mo; p = 0.00056) and a median PFS of 13 mo vs. 3 mo, p = 0.00175. In recurrent cases, nivolumab was associated with longer median OS (23 mo vs. 9 mo, p = 0.015) and PFS (11 mo vs. 3 mo, p = 0.019). irAEs occurred in four out of eleven of these cases, leading to nivolumab discontinuation; however, three of these four patients maintained durable disease control. A literature review identified generally favorable outcomes for ICIs in SNMM, although results were varied due to small sample sizes and heterogeneous treatment settings. Conclusions: Nivolumab was associated with longer survival in this small cohort in patients with SNMM, including those who discontinued therapy due to irAEs. Our data supports recent meta-analyses demonstrating a benefit of ICIs in SNMM. Full article

(This article belongs to the Special Issue Cancer Immunotherapy: Focus on Immune Checkpoint Inhibitors and Immune Modulators)

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24 pages, 1673 KB

Open AccessReview

Integrating Artificial Intelligence, Circulating Tumor DNA, and Real-World Evidence to Optimize Hematologic Clinical Trials: Toward Adaptive and Learning Trial Designs

by Abdurraouf Mokhtar Mahmoud, Jasmitaben Prakashbhai Touti, Syed Rubina Zaidi, Ahad Ahmed Kodipad and Clara Deambrogi

Cancers 2026, 18(7), 1173; https://doi.org/10.3390/cancers18071173 - 6 Apr 2026

Viewed by 1560

Abstract

The integration of emerging technologies and real-world data is transforming the landscape of hematologic clinical trials. Artificial intelligence (AI) offers remarkable capabilities for predictive modeling, patient stratification, and adaptive trial design, while circulating tumor DNA (ctDNA) provides a minimally invasive biomarker for disease [...] Read more.

The integration of emerging technologies and real-world data is transforming the landscape of hematologic clinical trials. Artificial intelligence (AI) offers remarkable capabilities for predictive modeling, patient stratification, and adaptive trial design, while circulating tumor DNA (ctDNA) provides a minimally invasive biomarker for disease monitoring, the early detection of relapse, and treatment response assessment. Concurrently, real-world evidence (RWE) complements traditional clinical trial data by capturing treatment effectiveness, safety, and patient outcomes in broader, heterogeneous populations. This review examines the synergistic potential of AI, ctDNA, and RWE to optimize trial design and decision-making in hematologic malignancies. We discuss methodological innovations, including AI-driven patient selection, ctDNA-guided adaptive interventions, and the incorporation of RWE for external control arms and post-marketing surveillance. Key challenges, such as data standardization, regulatory considerations, and ethical implications, are also addressed. By integrating these advanced tools, clinical trials in hematology can achieve greater efficiency, precision, and translatability, ultimately accelerating the development of personalized therapies and improving patient outcomes. Full article

(This article belongs to the Section Clinical Research in Cancer)

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22 pages, 3988 KB

Open AccessArticle

Dissecting Sex Chromosome and Hormonal Contributions to Urethane-Induced Lung Tumorigenesis Using the Four Core Genotypes Mouse Model

by Maksat Babayev, Omar A. Borges-Sosa, Carolyn D. Ekpruke, Erik Parker, Dustin Rousselle, Lyidia Dinwiddie, Rachel Alford, Shikha Sharma, Praveen Chirumamilla, Michelle C. Boulos, Aakash Parekh, Matthew L. Retzner, Catherine R. Sears, James E. Klaunig, Sarah Commodore and Patricia Silveyra

Cancers 2026, 18(7), 1172; https://doi.org/10.3390/cancers18071172 - 5 Apr 2026

Viewed by 982

Abstract

Background/Objectives: Sex differences in lung cancer incidence and outcomes are well recognized, yet the relative contributions of sex chromosomes and gonadal sex remain incompletely defined. We aimed to disentangle chromosomal complement and hormonal sex in urethane-induced lung tumorigenesis using the Four Core Genotypes [...] Read more.

Background/Objectives: Sex differences in lung cancer incidence and outcomes are well recognized, yet the relative contributions of sex chromosomes and gonadal sex remain incompletely defined. We aimed to disentangle chromosomal complement and hormonal sex in urethane-induced lung tumorigenesis using the Four Core Genotypes mouse model. Methods: Mice (6–8 weeks old) with independently varied chromosomal complement (XX vs. XY) and gonadal sex received urethane (1 g/kg body weight) weekly for 10 weeks and were evaluated after a 20-week latency period. Tumor multiplicity, tumor area, normalized tumor burden, and Ki-67 proliferation indices were quantified histologically. Hepatic Cyp2e1 expression was measured to assess carcinogen bioactivation. Tumor mutations were analyzed by Sanger sequencing. RAS Q61R immunoreactivity and ERK phosphorylation were evaluated to assess oncogenic signaling. Bronchoalveolar lavage fluid cellularity was analyzed. Survival was monitored. Statistical analyses tested the main effects of chromosomal complement, gonadal sex, and their interaction. Results: Tumor multiplicity (p = 0.0729), tumor area (p = 0.5302), normalized tumor burden (p = 0.5316), and Ki-67 indices (p = 0.6551) did not differ among genotypes. Hepatic Cyp2e1 expression was comparable across groups (genotype p = 0.076; treatment p = 0.445). Sanger sequencing confirmed canonical Kras Q61R mutations. Anti-RAS (Q61R) immunohistochemistry revealed a significant genotype effect on mutant RAS expression (F(3,23) = 3.48, p = 0.032), with the highest H-scores observed in XYF mice compared with male gonadal genotypes; ERK phosphorylation did not differ. Bronchoalveolar lavage fluid analysis revealed increased lymphocytes after urethane exposure without genotype-dependent effects. Survival differed significantly, with XX females demonstrating prolonged survival relative to XY males. Conclusions: Sex influenced survival independently of tumor burden, indicating that sex-associated differences in lung cancer outcomes are likely driven by systemic or microenvironmental factors rather than tumor-intrinsic growth mechanisms. Full article

(This article belongs to the Section Molecular Cancer Biology)

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19 pages, 552 KB

Open AccessReview

Pediatric Spinal Atypical Teratoid Rhabdoid Tumor: Recent Advances in Biology and Management Options

by Ruby Siada, Kaushik Banerjee, Payal Malhotra, Mohannad Ibrahim, Daniel C. Moreira, John R. Prensner and Santhosh A. Upadhyaya

Cancers 2026, 18(7), 1171; https://doi.org/10.3390/cancers18071171 - 5 Apr 2026

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Abstract

Atypical teratoid rhabdoid tumor (AT/RT) is a rare, highly aggressive embryonal central nervous system malignancy occurring predominately in infants and toddlers. Spinal AT/RT (spAT/RT) cases are even more limited, and as a result, little is known regarding prognostic factors and optimal treatment regimens. [...] Read more.

Atypical teratoid rhabdoid tumor (AT/RT) is a rare, highly aggressive embryonal central nervous system malignancy occurring predominately in infants and toddlers. Spinal AT/RT (spAT/RT) cases are even more limited, and as a result, little is known regarding prognostic factors and optimal treatment regimens. Molecularly, AT/RT is divided into three groups: AT/RT-SHH, AT/RT-TYR and AT/RT-MYC. spAT/RT is predominantly of the MYC subtype. Additionally, a third of patients with AT/RT have a germline Rhabdoid Tumor Predisposition Syndrome (RTPS) that increases the likelihood of developing additional rhabdoid tumors, including renal rhabdoid tumors. Due to the rarity of these tumors, there is a lack of consensus on treatment strategies to be employed. This review paper details the published literature on spAT/RT, with particular emphasis on the recent advances in understanding the biology of these aggressive tumors and currently available therapeutic options, and highlights the challenges associated with the management of this extremely rare condition. Full article

(This article belongs to the Special Issue Current Concept and Management of Pediatric ATRTs—2nd Edition)

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17 pages, 879 KB

Open AccessArticle

Prognostic Impact of the Lung Immune Prognostic Index in Metastatic Non-Small Cell Lung Cancer Patients Treated with Nivolumab

by Şahin Bedir, Tanju Kapağan, Yakup Bozkaya, Abdilkerim Oyman, Mehmet Cem Fidan, Murad Guliyev, Hamza Abbasov, Nebi Serkan Demirci, Hale Gülçin Yıldırım Doğan, Emir Çelik, Nilüfer Bulut and Gökmen Umut Erdem

Cancers 2026, 18(7), 1170; https://doi.org/10.3390/cancers18071170 - 5 Apr 2026

Viewed by 849

Abstract

Background: Immune checkpoint inhibitors (ICIs) have become a cornerstone in the treatment of advanced non-small cell lung cancer (NSCLC), yet substantial heterogeneity in clinical outcomes persists. Easily accessible biomarkers that can reliably stratify prognosis in real-world practice are still lacking. The Lung [...] Read more.

Background: Immune checkpoint inhibitors (ICIs) have become a cornerstone in the treatment of advanced non-small cell lung cancer (NSCLC), yet substantial heterogeneity in clinical outcomes persists. Easily accessible biomarkers that can reliably stratify prognosis in real-world practice are still lacking. The Lung Immune Prognostic Index (LIPI), integrating lactate dehydrogenase (LDH) and the derived neutrophil-to-lymphocyte ratio (dNLR), has emerged as a promising candidate, yet its clinical relevance remains incompletely defined. Methods: We conducted a multicenter retrospective analysis of 211 patients with metastatic NSCLC treated with second-line nivolumab between 2017 and 2025. Patients were categorized into three groups (good, intermediate, and poor) according to their LIPI score, and the relationships between LIPI and objective response, disease control, progression-free survival (PFS), and overall survival (OS) were analyzed. Results: LIPI stratification effectively discriminated patients into prognostically distinct groups. Objective response rates were comparable across LIPI categories and did not differ significantly. In contrast, disease control declined progressively with worsening LIPI scores, reaching statistical significance (p < 0.001). Overall survival was significantly worse in patients with poor LIPI, demonstrating a clear stepwise reduction from good to poor LIPI groups (p = 0.007). Although progression-free survival showed a consistent numerical decrease across LIPI categories, this trend did not achieve statistical significance. Conclusions: In patients with metastatic NSCLC receiving second-line nivolumab in a real-world setting, LIPI reliably stratified overall survival and disease control outcomes, despite limited association with early response or progression-free survival. Its simplicity and reliance on routinely available laboratory parameters support its use as a clinically meaningful prognostic tool in everyday practice. Full article

(This article belongs to the Section Cancer Biomarkers)

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24 pages, 3104 KB

Open AccessReview

Pathology of Cutaneous T Cell Lymphoma: A Narrative Review

by Ting Zhang, Yi Hu, Kexin Wang, Zhaohuai Zhang, Ying Wang, Yu Zhang and Zuotao Zhao

Cancers 2026, 18(7), 1169; https://doi.org/10.3390/cancers18071169 - 4 Apr 2026

Cited by 1 | Viewed by 2344

Abstract

Cutaneous T-cell lymphoma (CTCL) comprises a heterogeneous group of extranodal non-Hodgkin lymphomas. With the publication of the fifth edition of the World Health Organization Classification of Hematolymphoid Tumors, the diagnostic framework for CTCL has shifted from primarily morphologic phenotypes toward an emphasis on [...] Read more.

Cutaneous T-cell lymphoma (CTCL) comprises a heterogeneous group of extranodal non-Hodgkin lymphomas. With the publication of the fifth edition of the World Health Organization Classification of Hematolymphoid Tumors, the diagnostic framework for CTCL has shifted from primarily morphologic phenotypes toward an emphasis on molecular drivers. Current research suggests that malignant clones may arise from somatic mutations at the hematopoietic stem cell stage and may follow a continuous hematogenous dissemination model with bidirectional trafficking between the skin and systemic circulation. At the molecular level, genomic instability, often associated with somatic copy-number variations, may promote activation of the janus kinase-signal transducer and activator of transcription (JAK/STAT) signaling pathway through gene-dosage effects. In parallel, chromatin remodeling linked to EZH2 overexpression and reduced special SATB1 expression may support a Th2-polarized program. This phenotype may contribute to epidermal barrier impairment via cytokines such as Interleukins-4 (IL-4) and IL-13, potentially creating conditions permissive for Staphylococcus aureus colonization. Microbial superantigens and exotoxins may further contribute to tumor progression and therapeutic resistance by reinforcing JAK/STAT signaling, particularly STAT3, and reducing CD8+ T-cell–mediated immune surveillance. In the dermis, reprogramming of cancer-associated fibroblasts and polarization of macrophages toward an M2 phenotype may collectively contribute to an immunosuppressive niche. Emerging biomarkers, including CD74, and acquired resistance mechanisms after anti-C-C chemokine receptor 4 therapy further extend the translational relevance of recent pathologic findings. Overall, CTCL evolution appears to be a systemic process shaped by interactions between tumor-intrinsic genetic alterations and the skin microenvironment. Full article

(This article belongs to the Special Issue Advances in Pathology of Lymphoma and Leukemia)

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15 pages, 1370 KB

Open AccessArticle

Clinicopathological and Prognostic Characteristics of Gastric-Type Endocervical Adenocarcinoma: A Nested Case–Control Study

by Yang Liu, Yundi Hu, Hui Wang, Ling Qiu, Xiaomei Sun, Xuan Yin, Shen Luo, Yue Yin, Qing Cong, Xiang Tao, Yan Ning, Yan Zhao, Haiou Liu, Hua Jiang, Xiaolei Lin and Xin Wu

Cancers 2026, 18(7), 1168; https://doi.org/10.3390/cancers18071168 - 4 Apr 2026

Viewed by 942

Abstract

Background/Objectives: Gastric-type endocervical adenocarcinoma (G-EAC) is a rare, aggressive, and HPV-independent subtype of cervical cancer with a poor prognosis. Due to its rarity, existing literature is often limited by small sample sizes, which hinders the development of evidence-based clinical management strategies. This [...] Read more.

Background/Objectives: Gastric-type endocervical adenocarcinoma (G-EAC) is a rare, aggressive, and HPV-independent subtype of cervical cancer with a poor prognosis. Due to its rarity, existing literature is often limited by small sample sizes, which hinders the development of evidence-based clinical management strategies. This study aims to evaluate the clinicopathological features, prognostic factors, and responses to postoperative adjuvant therapy in a large cohort of G-EAC patients compared with those with usual endocervical adenocarcinoma (UEA). Methods: We conducted a nested case–control study within a prospectively maintained surgical cohort at a national referral center in China. The study population included 195 pathologically confirmed G-EAC cases and 765 UEA cases. Patients were followed longitudinally with comprehensive clinical and survival data collection. One-to-one propensity score matching (PSM) was performed to balance demographic, clinical, and treatment variables between the groups. Survival outcomes were compared using Kaplan–Meier analysis, and independent prognostic factors were identified via Cox regression. Results: G-EAC patients demonstrated significantly worse survival outcomes than matched UEA patients, with 3-year progression-free survival (PFS) of 66.1% vs. 79.8% (p = 0.014) and 3-year overall survival (OS) of 74.9% vs. 84.6% (p = 0.033). Parametrial involvement and pelvic lymph node metastasis were identified as independent risk factors for both recurrence and death (p < 0.05). Regarding adjuvant treatment, combined radiotherapy and chemotherapy significantly improved survival compared with single-modality treatments (PFS: 65.2% vs. 43.6%; OS: 74.3% vs. 54.5%; p < 0.05); however, G-EAC remained less responsive to these therapies than UEA. Conclusions: G-EAC exhibits more aggressive clinical behavior and poorer survival outcomes compared to UEA. While combined radiotherapy and chemotherapy offer survival benefits, outcomes remain suboptimal. These findings underscore the urgent need for early detection strategies and the development of more effective targeted therapies for this specific subtype. Full article

(This article belongs to the Section Cancer Pathophysiology)

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18 pages, 736 KB

Open AccessPerspective

Do We Need a New Diagnostic Model for Lung Cancer—Are We Ready? A Narrative Review of European Rapid Diagnostic Programs and an Operational Unified FTC-LCU Model

by Joanna Maksymowicz-Jaroszuk, Lukasz Minarowski and Robert Marek Mroz

Cancers 2026, 18(7), 1167; https://doi.org/10.3390/cancers18071167 - 4 Apr 2026

Viewed by 859

Abstract

Background: Lung cancer (LC) remains the leading cause of cancer-related mortality worldwide. Survival outcomes are strongly stage-dependent. Many patients are diagnosed at advanced stages due to pre-clinical and diagnostic delays. While advances in imaging, bronchoscopic techniques, molecular diagnostics, and systemic therapies have improved [...] Read more.

Background: Lung cancer (LC) remains the leading cause of cancer-related mortality worldwide. Survival outcomes are strongly stage-dependent. Many patients are diagnosed at advanced stages due to pre-clinical and diagnostic delays. While advances in imaging, bronchoscopic techniques, molecular diagnostics, and systemic therapies have improved individualized treatment, system-level delays continue to limit their impact. Aim of the study: The aim of this narrative review is a synthesis with an implementation-oriented framework proposal. Part I synthesizes the peer-reviewed literature, Part II presents an operational framework integrating a Fast Trac Clinic (FTC) and a network of Lung Cancer Units (LCUs) including proposed turnaround-time (TAT) goals. Methods: A narrative review of the literature of selected European policy documents addressing diagnostic delays, rapid-access lung cancer pathways, and coordinated care models was conducted. Results: European models demonstrate that structured referral criteria, centralized coordination, and predefined interval targets can achieve the first specialist assessment within 7–10 days and the completion of diagnostics within 21–28 days in optimized settings. Key determinants of timeliness include: direct primary care referral, parallel diagnostic processes, prioritized pathology and molecular testing, and multidisciplinary team (MDT) assessment. We propose operational TAT targets for chest CT, PET-CT, histopathology, NGS, PFTs, and MDT decision-making. Conclusions: Reducing avoidable diagnostic and therapeutic delays in LC requires a coordinated, system-level approach. A standardized FTC-LCU pathway with explicit TAT benchmarks, multidisciplinary governance, and digital support infrastructure may improve diagnostic efficiency, increase the proportion of patients treated at earlier stages, and enhance patient experience. Prospective evaluation of implementation impact on stage distribution and survival is advised. Full article

(This article belongs to the Section Cancer Causes, Screening and Diagnosis)

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26 pages, 1840 KB

Open AccessReview

Human-Centric Modeling in Metastatic Breast Cancer: Organoids, Organ-on-Chip Systems, and New Approach Methodologies in the Post-FDA Modernization Act 2.0 Era

by Hissah Alatawi, Haritha H. Nair, Asif Raza, Emiliana Velez, Arun K. Sharma and Satya Narayan

Cancers 2026, 18(7), 1166; https://doi.org/10.3390/cancers18071166 - 4 Apr 2026

Viewed by 1240

Abstract

Metastatic breast cancer (MBC) remains an overwhelming clinical challenge due to its inherent clonal evolution and the frequent development of drug resistance. A significant hurdle in therapeutic discovery is the reliance on traditional 2D cell cultures and animal models, which often fail to [...] Read more.

Metastatic breast cancer (MBC) remains an overwhelming clinical challenge due to its inherent clonal evolution and the frequent development of drug resistance. A significant hurdle in therapeutic discovery is the reliance on traditional 2D cell cultures and animal models, which often fail to accurately replicate human tumor pathophysiology or predict clinical responses. Consequently, the field of oncology is increasingly exploring a transition towards human-centric research that prioritizes biological data derived directly from patients. Considering the FDA Modernization Act 2.0 and the 2025 FDA Roadmap, frameworks are being established to explore the integration of new approach methodologies (NAMs)—including patient-derived organoids (PDOs) and organ-on-a-chip (OoC) systems—into the drug development pipeline. This review examines how these platforms aim to better simulate the human physiological environment by capturing the complex architecture and microenvironment of the tumor. We further discuss how the integration of these models with Artificial Intelligence (AI), spatial multi-omics, and real-time liquid biopsies is being investigated to enhance the speed and precision of therapeutic testing. While still in the translational phase, emerging evidence suggests that human-centric platforms may eventually support rapid functional drug screening, potentially informing patient treatment responses within clinically relevant timeframes. Strengthening the biological link between the patient and their longitudinal data represents a promising strategy to address the complexities of MBC and improve clinical outcomes. These human-centric platforms preserve patient-specific tumor heterogeneity, recapitulate microenvironmental interactions, and enable functional drug testing under physiologically relevant conditions, thereby improving translational accuracy compared to conventional models. Full article

(This article belongs to the Special Issue Advancements in Preclinical Models for Solid Cancers)

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25 pages, 5102 KB

Open AccessReview

The Evolution of the Management of Dysplasia in Ulcerative Colitis

by Adrienne L. Vickers and Alessandro Fichera

Cancers 2026, 18(7), 1165; https://doi.org/10.3390/cancers18071165 - 4 Apr 2026

Viewed by 1487

Abstract

With modern medicine and a better understanding of the ulcerative colitis disease process, there have been many changes in how we manage ulcerative colitis-related dysplasia over the past 20 years. One of the biggest concerns for these patients, given the inflammatory nature of [...] Read more.

With modern medicine and a better understanding of the ulcerative colitis disease process, there have been many changes in how we manage ulcerative colitis-related dysplasia over the past 20 years. One of the biggest concerns for these patients, given the inflammatory nature of their disease, is the progression from chronic inflammation to cancer. Patients with ulcerative colitis have about a 2.4-fold increased risk of developing colorectal cancer compared to the general population, which is concerning since colorectal cancer is the 2nd leading cause of cancer-related deaths in the United States. Traditionally, surgery was the preferred treatment for ulcerative colitis patients with dysplasia, but now, with advances in surveillance such as high-definition colonoscopy and chromoendoscopy, the management approach is more nuanced. Understanding the risk for different individuals within this patient population is key to comprehensive and personalized care management. In this review article, we will explore risk factors, surveillance methods, and classification. Full article

(This article belongs to the Special Issue IBD-Associated Cancer)

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14 pages, 1010 KB

Open AccessArticle

Hemophagocytic Lymphohistiocytosis Associated with Immune Checkpoint Inhibitors: A Pharmacovigilance Analysis of Spontaneous Reports

by Suleyman Sami Guzel, Kubilay Tay, Ebru Cicek, Seda Jeral Evinc, Suheyla Atak, Cigdem Papila, Nebi Serkan Demirci and Ozkan Alan

Cancers 2026, 18(7), 1164; https://doi.org/10.3390/cancers18071164 - 4 Apr 2026

Cited by 3 | Viewed by 1061

Abstract

Objectives: Hemophagocytic lymphohistiocytosis (HLH) is a rare but life-threatening hyperinflammatory syndrome increasingly reported with immune checkpoint inhibitors (ICIs). However, comparative real-world data across different ICI classes and treatment strategies are limited. This study aimed to characterize HLH reporting patterns associated with ICIs and [...] Read more.

Objectives: Hemophagocytic lymphohistiocytosis (HLH) is a rare but life-threatening hyperinflammatory syndrome increasingly reported with immune checkpoint inhibitors (ICIs). However, comparative real-world data across different ICI classes and treatment strategies are limited. This study aimed to characterize HLH reporting patterns associated with ICIs and to compare disproportionality signals among PD-1 inhibitors, PD-L1 inhibitors, and combination regimens using the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS). Methods: A retrospective pharmacovigilance analysis was performed using FAERS reports submitted between 2013 and 2025. HLH-related cases were identified using core Medical Dictionary for Regulatory Activities (MedDRA) Preferred Terms. Reporting odds ratios (RORs) with 95% confidence intervals (Cis) were calculated to assess disproportionality across ICI treatment strategies, with ICI monotherapy as the reference. Restricted analyses compared PD-1 inhibitors, PD-L1 inhibitors, and ICI plus CTLA-4 inhibitor therapy. Results: A total of 733 HLH-related reports associated with ICIs were identified. The median age was 65 years (range 1–92), and 54.9% of patients were male. Lung cancer (34.4%) and melanoma (16.0%) were the most frequently reported malignancies. ICI monotherapy accounted for 34.7% of cases, while combination regimens included ICI plus chemotherapy (31.6%), ICI plus targeted therapy (17.8%), and ICI plus CTLA-4 inhibitors (15.9%). All cases were classified as serious adverse events; hospitalization occurred in 69.2% and death in 25.1%. Compared with monotherapy, combination regimens showed higher reporting odds of HLH, with the strongest signal for ICI plus targeted therapy (ROR 2.17, 95% CI 1.72–2.73). PD-1 inhibitors demonstrated higher reporting odds than PD-L1 inhibitors (ROR 1.86, 95% CI 1.41–2.46). Conclusions: This large real-world pharmacovigilance analysis demonstrates differential HLH reporting patterns across ICI classes and treatment strategies. Higher reporting odds with combination regimens and PD-1 inhibitors highlight the need for heightened clinical vigilance, particularly in combination treatment settings. Full article

(This article belongs to the Section Cancer Immunology and Immunotherapy)

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16 pages, 1451 KB

Open AccessArticle

Intranuclear Peripheral Overexpression of Pituitary-Tumor-Transforming Gene 1: Immunohistochemical Biomarker of Lymph Node Involvement in Testicular Seminoma

by Edoardo Vergani, Francesco Pierconti, Carlotta Pozza, Elisabetta Merenda, Paola Girardi, Marta Tenuta, Roberta Benvenuto, Emanuela Teveroni, Gaetano Gulino, Giorgio Franco, Fabio Massimo Magliocca, Bernardo Rocco, Andrea Isidori, Alfredo Pontecorvi and Domenico Milardi

Cancers 2026, 18(7), 1163; https://doi.org/10.3390/cancers18071163 - 4 Apr 2026

Viewed by 723

Abstract

Background/Objectives: Testicular germ cell tumors, particularly seminoma, represent the leading cause of cancer in men aged 15–40 years. The decision about adjuvant therapy relies on histological features with uncertain prognostic value. The Pituitary-Tumor-Transforming Gene 1 (PTTG1), which encodes the securin protein, is [...] Read more.

Background/Objectives: Testicular germ cell tumors, particularly seminoma, represent the leading cause of cancer in men aged 15–40 years. The decision about adjuvant therapy relies on histological features with uncertain prognostic value. The Pituitary-Tumor-Transforming Gene 1 (PTTG1), which encodes the securin protein, is crucial in sister chromatid separation. Our previous in vitro studies demonstrated that PTTG1 nuclear expression promotes invasiveness, dedifferentiation, and neolymphangiogenesis in testicular seminoma. Methods: We conducted a hypothesis-generating retrospective observational study on 51 patients (aged 23–68) with testicular seminoma, with (43%) or without (57%) lymph node involvement, evaluating potential correlations between PTTG1 and currently known prognostic factors. Clinical and pathological data were collected, including lymph node involvement, recurrence, necrosis, rete testis invasion, vascular invasion, and adipose tissue invasion. An immunohistochemical scoring system assessing intranuclear PTTG1 expression was developed. Results: The PTTG1 score was related to lymph node metastasis and adipose tissue invasion. ROC curve analysis showed that the PTTG1 immunohistochemical score showed good discriminatory ability in identifying lymph node involvement (AUC = 0.939); the optimal cut-off was 4.0 (sensitivity 90.5%; specificity 57.1%), while the ROC curve for adipose tissue invasion was inadequate. Lymph node metastasis also correlated with necrosis; however, logistic regression confirmed that PTTG1 score was independently associated with nodal involvement (p = 0.002), regardless of tumor size and necrosis. Conclusions: Our findings suggest a correlation between PTTG1 expression and lymphadenopathy at diagnosis, independent of tumor size and T stage. It may reflect biological features associated with lymphatic dissemination and requires further investigation in larger prospective studies. Full article

(This article belongs to the Special Issue Solid Tumors, with a Focus on Urological Cancers: From Molecular Mechanisms to Predictive Biomarkers)

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38 pages, 682 KB

Open AccessReview

Photodynamic Therapy-Based Strategies Targeted at Cancer Stem Cells: A Scoping Review

by Beatriz Serambeque, Inês Dias, Catarina Mestre, Carlos Miguel Marto, Maria Filomena Botelho, Maria João Carvalho and Mafalda Laranjo

Cancers 2026, 18(7), 1162; https://doi.org/10.3390/cancers18071162 - 3 Apr 2026

Cited by 1 | Viewed by 1097

Abstract

A major challenge in cancer treatment is the presence of cancer stem cells (CSC), which play a significant role in therapeutic resistance, metastatic progression, and tumor relapse, highlighting their importance as therapeutic targets. Photodynamic therapy (PDT) can be a valuable strategy for targeting [...] Read more.

A major challenge in cancer treatment is the presence of cancer stem cells (CSC), which play a significant role in therapeutic resistance, metastatic progression, and tumor relapse, highlighting their importance as therapeutic targets. Photodynamic therapy (PDT) can be a valuable strategy for targeting CSC by increasing reactive oxygen species via light-activated photosensitizers, thereby counteracting CSC features of resistance. Therefore, this manuscript reviews the existing evidence on PDT-based approaches targeted at CSC. The literature search was conducted using the Medline (through PubMed), Web of Science, and Embase databases. The inclusion criteria were in vitro, in vivo, and clinical studies addressing PDT-based therapeutic strategies targeting CSC. A total of 37 publications were included in this review. From this analysis, we identified several studies with CSC-associated targets, delivery of PDT systems to CSC, novel nanoplatforms that disrupted the CSC microenvironment, and combined strategies to enhance PDT efficacy. The existing strategies have shown success in reducing CSC populations across different cancers by decreasing viability and tumor growth, as well as limiting stemness properties. However, some technical and biological constraints can limit translation, and, to the best of our knowledge, no clinical studies have been reported. Full article

(This article belongs to the Special Issue New Molecular Targets and Emerging Approaches to Target Cancer Stem Cells)

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19 pages, 3003 KB

Open AccessArticle

Machine-Learning-Based Survival Prediction in Glioblastoma Using Graph-Theoretical Analysis of Structural Network Alterations

by Andreas Stadlbauer, Stefan Oberndorfer, Gertraud Heinz, Franz Marhold, Thomas M. Kinfe, Mario Dorostkar, Oliver Schnell, Uwe Meyer-Bäse and Anke Meyer-Bäse

Cancers 2026, 18(7), 1161; https://doi.org/10.3390/cancers18071161 - 3 Apr 2026

Cited by 1 | Viewed by 1106

Abstract

Background: Glioblastoma is an extremely aggressive brain tumor that diffusely infiltrates white matter and alters large-scale brain connectivity. Most prognostic models focus on localized tumor features and clinical variables, overlooking broader effects on the brain’s structural connectome. This study addressed this limitation [...] Read more.

Background: Glioblastoma is an extremely aggressive brain tumor that diffusely infiltrates white matter and alters large-scale brain connectivity. Most prognostic models focus on localized tumor features and clinical variables, overlooking broader effects on the brain’s structural connectome. This study addressed this limitation by integrating graph-theoretical analysis of preoperative diffusion tensor imaging (DTI)-derived structural connectomes with machine learning (ML) to improve prediction of overall survival (OS) in newly diagnosed glioblastoma. Methods: Preoperative DTI data from 871 glioblastoma patients from the UPenn-GBM and UCSF-PDGM cohorts were processed to construct whole-brain structural connectomes weighted by tract count and quantitative anisotropy (QA). Global and nodal graph-theoretical network metrics were extracted and combined with demographic and clinical information. Ten ML models were trained and validated on 784 patients (90% of the cohort). The three best-performing algorithms were tested on a held-out cohort of 87 patients (10%). Results: Random forest, adaptive boosting, and KStar showed the strongest validation performance. In held-out internal testing, random forest models using degree and QA-weighted strength achieved accuracies of 0.862 and 0.874, with AUROCs of 0.929 and 0.909, for predicting OS beyond one year. Strength and clustering coefficient were key predictors, with over two-thirds of significant nodes localized in the temporal lobe, particularly the parahippocampal, and superior, middle, and inferior temporal gyri. Conclusions: Graph-theoretical quantification of structural brain network disruption combined with ML allows accurate prediction of OS in glioblastoma. These results support a network-based conceptualization of the disease and indicate that connectome-derived metrics may complement established prognostic frameworks. Full article

(This article belongs to the Special Issue Advances in Neuro-Oncological Imaging (2nd Edition))

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13 pages, 1139 KB

Open AccessArticle

Comparative Effectiveness of Pomalidomide-Based Regimens in Relapsed/Refractory Multiple Myeloma: A Multicenter Real-World Analysis in China

by Shan Gao, Junling Zhuang, Aijun Liu, Dongmei Wang, Wei Wang, Xin Li, Zhihong Wang, Meiyun Fang, Ming Gong, Zhilin Jia, Sun Wu, Zheng Xu, Genjie Wang and Li Bao

Cancers 2026, 18(7), 1160; https://doi.org/10.3390/cancers18071160 - 3 Apr 2026

Viewed by 1012

Abstract

Background: Although multiple pomalidomide-based combinations are active in relapsed and/or refractory multiple myeloma (RRMM), comparative data to guide regimen selection remain limited. Methods: A total of 230 patients with RRMM from 12 centers in China who received pomalidomide-based regimens were included [...] Read more.

Background: Although multiple pomalidomide-based combinations are active in relapsed and/or refractory multiple myeloma (RRMM), comparative data to guide regimen selection remain limited. Methods: A total of 230 patients with RRMM from 12 centers in China who received pomalidomide-based regimens were included in this retrospective analysis. Overall response rate (ORR) and progression-free survival (PFS) were compared across regimens incorporating bortezomib or ixazomib (V/IPD), carfilzomib (KPD), or daratumumab (DPD), and multivariable analyses were performed to identify prognostic factors. Results: The overall ORR was 73.9%, with rates of 63%, 79%, and 85% in the V/IPD (n = 66), KPD (n = 69), and DPD (n = 95) cohorts, respectively. ORR differed significantly between V/IPD and DPD (p = 0.0165), driven by a higher proportion of ≥VGPR in the DPD group. The median PFS for the entire cohort was 17.4 months (95% CI: 13.7–20.1), compared with 15.4 months (95% CI: 12.8–20.5), 14.2 months (95% CI: 6.9–not estimable), and 19.2 months (95% CI: 15.1–24.9) for V/IPD, KPD, and DPD, respectively, without significant differences. In multivariable analysis, DPD was associated with improved ORR (HR 4.83, p < 0.001) but not with PFS. R-ISS stage III predicted inferior response (HR 0.35, p = 0.04), whereas ≥3 prior lines of therapy correlated with shorter PFS (HR 1.77, p = 0.012). Adverse events were predominantly hematologic, with limited grade 3–4 toxicity and no treatment-related mortality. Conclusions: This multicenter real-world analysis clarifies the relative positioning of commonly used pomalidomide-based regimens in RRMM and underscores the importance of treatment timing and disease stage in optimizing outcomes. Full article

(This article belongs to the Topic Myeloma and Leukemia—Challenges and Current Treatment Options: 2nd Edition)

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17 pages, 5312 KB

Open AccessArticle

lncRNA NAS1 Deficiency Drives Cisplatin Resistance via NR2F1-Mediated TGFB1/NF-κB Signaling Axis in NSCLC

by Xianrong Lin, Yuxin Wu, Qi Wu, Wenjun Tao, Jun Zhang and Jun Zhou

Cancers 2026, 18(7), 1159; https://doi.org/10.3390/cancers18071159 - 3 Apr 2026

Viewed by 881

Abstract

Background: Cisplatin resistance remains a major challenge in the treatment of non-small cell lung cancer (NSCLC). Although long non-coding RNAs (lncRNAs) have been implicated in chemotherapy resistance, their specific roles and underlying mechanisms remain incompletely understood. This study aimed to identify lncRNAs associated [...] Read more.

Background: Cisplatin resistance remains a major challenge in the treatment of non-small cell lung cancer (NSCLC). Although long non-coding RNAs (lncRNAs) have been implicated in chemotherapy resistance, their specific roles and underlying mechanisms remain incompletely understood. This study aimed to identify lncRNAs associated with cisplatin resistance in NSCLC and to elucidate the role and mechanism of NR2F1-AS1 (NAS1) in this process. Methods: Cisplatin-resistant NSCLC cell lines were established and subjected to transcriptome-wide RNA sequencing. NAS1 expression was validated by quantitative real-time PCR, and its clinical relevance was assessed using The Cancer Genome Atlas (TCGA) dataset. NAS1 and NR2F1 knockdown, together with NR2F1 overexpression and rescue experiments, were performed to evaluate their effects on cisplatin sensitivity. Downstream mechanisms were investigated by public dataset analysis, qPCR, and Western blotting, and NF-κB signaling was functionally assessed using the inhibitor DHMEQ. Results:NAS1 was consistently downregulated in multiple cisplatin-resistant NSCLC cell lines and was also decreased in NSCLC tissues. NAS1 knockdown enhanced cisplatin resistance. Mechanistically, loss of NAS1 reduced NR2F1 protein expression without significantly affecting its mRNA level, indicating translational regulation. NR2F1 downregulation also conferred cisplatin resistance, phenocopying the effect of NAS1 loss, whereas NR2F1 re-expression restored cisplatin sensitivity. Further analyses identified TGFB1 as a downstream effector derepressed by loss of the NAS1-NR2F1 axis, leading to activation of NF-κB signaling. Inhibition of NF-κB partially reversed cisplatin resistance in resistant cells. Conclusions: Collectively, our findings delineate a NAS1/NR2F1/TGFB1/NF-κB signaling axis critical for cisplatin resistance in NSCLC, revealing a potential therapeutic target for overcoming platinum resistance. Full article

(This article belongs to the Section Molecular Cancer Biology)

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13 pages, 637 KB

Open AccessReview

Regional Anesthesia and the Perioperative Inflammatory Window in Cancer Surgery: From Surgical Stress to Immunometabolic Reprogramming

by Tomasz Reysner and Malgorzata Reysner

Cancers 2026, 18(7), 1158; https://doi.org/10.3390/cancers18071158 - 3 Apr 2026

Viewed by 1058

Abstract

The impact of anesthetic technique on long-term oncologic outcomes remains controversial. While early observational data suggested that regional anesthesia might reduce cancer recurrence, large randomized trials have failed to demonstrate consistent survival benefits. This apparent contradiction may not reflect biological neutrality, but rather [...] Read more.

The impact of anesthetic technique on long-term oncologic outcomes remains controversial. While early observational data suggested that regional anesthesia might reduce cancer recurrence, large randomized trials have failed to demonstrate consistent survival benefits. This apparent contradiction may not reflect biological neutrality, but rather a mismatch between trial design and the inflammatory biology of the perioperative period. Surgical resection provokes an acute and intense inflammatory surge characterized by sympathetic activation, cytokine release, neutrophil extracellular trap formation, endothelial activation, and transient suppression of cellular immunity. During this perioperative inflammatory window, circulating tumor cells encounter a biologically permissive microenvironment that may facilitate immune evasion, adhesion, and early metastatic niche establishment. The magnitude of this inflammatory response varies across patients and may represent a critical, yet under-recognized, determinant of tumor–host dynamics. Anesthetic and analgesic strategies influence this inflammatory cascade. By attenuating nociceptive signaling and sympathetic activation, regional anesthesia may modulate perioperative immune and immunometabolic pathways. However, it should not be framed as an anti-cancer therapy per se, but rather as a potential regulator of the transient inflammatory milieu that shapes early oncologic biology. We propose that prior neutral trials may reflect methodological misalignment, including heterogeneous tumor populations, absence of inflammatory stratification, and reliance on distant survival endpoints without mechanistic correlates. Future investigations should integrate perioperative immune phenotyping, inflammatory biomarkers, and tumor subtype stratification to determine whether modulation of acute surgical inflammation meaningfully alters early tumor–host interactions. Reconceptualizing the perioperative period as a biologically active inflammatory interface may refine the anesthesiologist’s role within perioperative oncology and open new avenues for precision-based perioperative modulation. Full article

(This article belongs to the Special Issue Role of Inflammation in Cancer)

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29 pages, 45971 KB

Open AccessArticle

Dual-Tracer Imaging and Deep Learning for Real-Time Prediction of Lymph Node Metastasis in cN0 Papillary Thyroid Carcinoma

by Jing Zhou, Yuchen Zhuang, Qian Xiao, Shiying Yang, Zhuolin Dai, Chun Huang, Chang Deng, Lin Chun, Han Gao and Xinliang Su

Cancers 2026, 18(7), 1157; https://doi.org/10.3390/cancers18071157 - 3 Apr 2026

Viewed by 865

Abstract

Background: Occult lymph node metastasis (LNM) occurs in 30–80% of patients with clinically node-negative papillary thyroid carcinoma (cN0-PTC), partly owing to the limited sensitivity of current preoperative nodal assessment, and may contribute to postoperative recurrence. Conventional sentinel lymph node (SLN) biopsy, typically [...] Read more.

Background: Occult lymph node metastasis (LNM) occurs in 30–80% of patients with clinically node-negative papillary thyroid carcinoma (cN0-PTC), partly owing to the limited sensitivity of current preoperative nodal assessment, and may contribute to postoperative recurrence. Conventional sentinel lymph node (SLN) biopsy, typically performed with a single tracer, has limited reliability for detecting occult metastatic nodes, which can result in either overtreatment or undertreatment with lymph node dissection. We aimed to develop a highly accurate multimodal prediction framework to accurately identify second-echelon lymph node metastasis (SeLNM) and non-sentinel lymph node metastasis (NsLNM). Methods: We prospectively enrolled 301 patients with cN0-PTC between April and October 2024, of whom 131 met the inclusion criteria. Intraoperatively, a dual-tracer technique combining carbon nanoparticles and indocyanine green was applied, and near-infrared imaging was used to record the entire SLN visualization process in real time. For each case, a 3 min video clip (150 frames) was captured. Two senior surgeons delineated regions of interest to generate 19,650 mask images. A total of 2048 spatial features and 20 temporal features were extracted, combined with 32 clinical variables, including demographics, ultrasound characteristics, and gene mutation status. Nine deep learning models were developed and evaluated using 10-fold cross-validation. Model performance was quantified using receiver operating characteristic curves, decision curve analysis curves, calibration curves, precision–recall curves, learning curves, and 12 metrics. Statistical comparisons were performed using the DeLong test, and models were further evaluated using a probability-based ranking approach. Shapley Additive Explanations (SHAP) analysis was applied to interpret key predictive features. The primary outcomes were SeLNM and NsLNM, defined based on postoperative histopathology. Results: The Long Short-Term Memory (LSTM) + Transformer model showed the best performance for both prediction tasks, with stable AUCs across training and testing (SeLNM: 0.980/0.982; NsLNM: 0.986/0.983). In the testing set, the model reached the same accuracy for both outcomes (94.7%) and showed strong sensitivity/specificity for SeLNM (94.7%/94.6%) and NsLNM (96.4%/91.5%). SHAP analysis indicated that time-series fluorescence flow features were the most influential predictors, followed by spatial structural features and SLN status. Conclusions: Dual-tracer SLN mapping with deep learning demonstrated encouraging intraoperative prediction of lymph node metastasis with interpretable features in this single-center cohort. Independent multicenter validation and prospective outcome studies are needed before considering clinical adoption. Full article

(This article belongs to the Section Cancer Informatics and Big Data)

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17 pages, 443 KB

Open AccessArticle

Impact of Time of Administration, Fasting, and a Low-Carbohydrate Diet on Alpelisib-Associated Hyperglycemia and Efficacy: A Pilot Randomized Controlled Phase IIb Trial

by Eduard Vrdoljak, Marija Pancirov, Josipa Flam, Dora Čerina Pavlinović, Matea Jakas Vučić, Marica Barać, Natalija Dedić Plavetić, Paula Podolski, Mladen Krnić and Žarko Bajić

Cancers 2026, 18(7), 1156; https://doi.org/10.3390/cancers18071156 - 3 Apr 2026

Viewed by 752

Abstract

Background: Alpelisib plus fulvestrant improves outcomes in PIK3CA-mutated, hormone receptor-positive, HER2-negative metastatic breast cancer. However, on-target hyperglycemia often leads to dose modification or discontinuation. We aimed primarily to determine whether evening alpelisib after a ≥5 h fast with low-carbohydrate guidance reduces [...] Read more.

Background: Alpelisib plus fulvestrant improves outcomes in PIK3CA-mutated, hormone receptor-positive, HER2-negative metastatic breast cancer. However, on-target hyperglycemia often leads to dose modification or discontinuation. We aimed primarily to determine whether evening alpelisib after a ≥5 h fast with low-carbohydrate guidance reduces severe hyperglycemia versus standard morning dosing, and secondarily, to assess time to first grade 3–4 hyperglycemia, efficacy, and quality of life (QoL). Methods: ITACA was an open-label, randomized, phase IIb trial in three Croatian centers. Patients progressing on endocrine therapy were randomized 1:1 to evening alpelisib 300 mg after a ≥5 h fast with low-carbohydrate guidance or standard morning alpelisib, both with fulvestrant. The primary endpoint was the exposure-adjusted incidence rate (EAIR) of first grade 3–4 hyperglycemia within 90 days or 30 days post-discontinuation. Secondary endpoints were time to first grade 3–4 hyperglycemia, efficacy, and QoL. Results: Forty-two patients were randomized (21 per arm). Median age was 60 vs. 63 years in the evening vs. morning arms. In the safety set, EAIR of first grade 3–4 hyperglycemia was 378 vs. 742 per 100 person-years (11/21 vs. 14/20 patients with ≥1 event, unadjusted IRR 0.51, 95% CI 0.23–1.12). Adjusted Poisson models favored evening dosing. Analyses suggested delayed onset (median 73 vs. 9.5 days), with no detriment in efficacy or QoL. Conclusions: Evening alpelisib preceded by fasting and low-carbohydrate guidance may improve metabolic tolerability without compromising efficacy or QoL. These findings support evaluation in a larger trial incorporating prospective metabolic adherence and pharmacokinetic assessments. Full article

(This article belongs to the Special Issue Systemic Treatment for Breast Cancer)

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18 pages, 692 KB

Open AccessReview

From Pixels to Prediction: Developing Integrated AI Foundation Models for Personalized Thyroid Cancer Care

by Jae Hyun Park, Younghyun Park, Yong Moon Lee, Sejung Yang and Jong Ho Yoon

Cancers 2026, 18(7), 1155; https://doi.org/10.3390/cancers18071155 - 3 Apr 2026

Cited by 1 | Viewed by 939

Abstract

Background: Thyroid cancer incidence continues to rise globally, yet current diagnostic methods, reliant on ultrasound-guided fine-needle aspiration, suffer from substantial inter-observer variability and indeterminate results. Objective: This review explores the transformative potential of integrated artificial intelligence (AI) foundation models in thyroid [...] Read more.

Background: Thyroid cancer incidence continues to rise globally, yet current diagnostic methods, reliant on ultrasound-guided fine-needle aspiration, suffer from substantial inter-observer variability and indeterminate results. Objective: This review explores the transformative potential of integrated artificial intelligence (AI) foundation models in thyroid cancer management. We propose a paradigm shift using foundation models—large-scale, multimodal architectures pre-trained on diverse datasets—to bridge the gap between initial pixels and long-term prognostic prediction. Proposed Models: We introduce two integrated conceptual frameworks: ThyroSight-Prognos for high-precision assessment in specialized tertiary settings and SonoPredict-AI for cost-effective screening in primary care. Key Innovations: By synthesizing data from ultrasound, pathology (WSI), genomics, and clinical parameters through explainable AI (XAI), these models aim to reduce unnecessary surgeries and personalize treatment pathways. Challenges and Outlook: This paper addresses critical implementation challenges, including data heterogeneity, hardware requirements, and regulatory trust, ultimately providing a strategic blueprint for future multi-center prospective clinical validation to revolutionize thyroid care through precision oncology. Full article

(This article belongs to the Special Issue The Changing Paradigms in the Management of Thyroid Cancer)

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Cancers, Volume 18, Issue 7 (April-1 2026) – 138 articles

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