Cancers

17 pages, 404 KB

Open AccessReview

Neoadjuvant Therapies for Prostate Cancer–Current Paradigms and Future Directions

by Kieran Sandhu, Abdullah Al-Khanaty, David Hennes, David Chen, Eoin Dinneen, Carlos Delgado, Nathan Lawrentschuk, Renu S. Eapen, Declan G. Murphy and Marlon Perera

Cancers 2026, 18(1), 65; https://doi.org/10.3390/cancers18010065 - 24 Dec 2025

Abstract

High-risk and locally advanced prostate cancer represents 20–25% of new diagnoses of prostate cancer and is associated with high rates of recurrence, morbidity, and mortality. The neoadjuvant window provides a unique opportunity for systemic control prior to definitive therapy with radical prostatectomy or [...] Read more.

High-risk and locally advanced prostate cancer represents 20–25% of new diagnoses of prostate cancer and is associated with high rates of recurrence, morbidity, and mortality. The neoadjuvant window provides a unique opportunity for systemic control prior to definitive therapy with radical prostatectomy or radiotherapy (RT). Early trials with first-generation androgen deprivation therapy (ADT) achieved pathological downstaging but no survival benefit. In the 2000s, the advent of chemohormonal regimes using docetaxel provided excitement but mixed results tempered expectations and is now not recommended prior to surgery. Second-generation androgen receptor pathway inhibitors (ARPIs) combined with ADT have demonstrated significant survival benefit in metastatic prostate cancer and are currently being evaluated in large phase III trials in the neoadjuvant setting. RT remains an alternative curative modality, and recent data highlights similar issues to surgery in eradicating micrometastatic disease despite excellent local control. This has driven parallel efforts to evaluate intensified systemic therapy in the pre-RT/neoadjuvant settings. In addition to the excitement surrounding ARPIs, radioligand therapy, such as [¹⁷⁷Lu]Lu-PSMA-617 has shown promise in the neoadjuvant setting and continues to be investigated. Future research aims to incorporate genomic and molecular factors to enable personalised neoadjuvant therapies by identifying damage immunologically responsive subtypes that may derive greater benefit from immune-directed therapies in the peri-operative setting. This narrative review synthesises current evidence for neoadjuvant therapies in high-risk prostate cancer and future directions. Full article

(This article belongs to the Special Issue Neoadjuvant Therapy for Urologic Cancer)

12 pages, 750 KB

Open AccessArticle

Ten-Year Follow-Up of Mammography and Ultrasonography for Detection of Locoregional Breast Cancer Recurrence in Asian Female Patients

by Joon Suk Moon, In Hee Lee, Byeongju Kang, Ho Yong Park, Hye Jung Kim, Won Hwa Kim, Yee Soo Chae, Soo Jung Lee and Jeeyeon Lee

Cancers 2026, 18(1), 64; https://doi.org/10.3390/cancers18010064 - 24 Dec 2025

Abstract

Background: Breast cancer requires long-term surveillance, as recurrence and mortality risks extend beyond 10 years. Mammography (MMG) is the standard imaging modality; however, its effectiveness is reduced in Asian women owing to dense breast tissue. The optimal timing of surveillance MMG after breast-conserving [...] Read more.

Background: Breast cancer requires long-term surveillance, as recurrence and mortality risks extend beyond 10 years. Mammography (MMG) is the standard imaging modality; however, its effectiveness is reduced in Asian women owing to dense breast tissue. The optimal timing of surveillance MMG after breast-conserving surgery remains unclear, particularly the value of routine 6-month MMG. We evaluated the roles of MMG and ultrasound in detecting ipsilateral and contralateral breast cancer recurrence after breast-conserving surgery. Methods: This retrospective study included 961 patients with operable breast cancer who underwent breast-conserving surgery with or without axillary surgery between 2011 and 2015 at Kyungpook National University Chilgok Hospital. Surveillance consisted of biannual imaging for the first 2 years, followed by annual imaging for up to 10 years. Ipsilateral and contralateral breast cancer recurrences were analyzed according to detection modality, including MMG and ultrasound. Multivariate Cox proportional hazards regression analysis was performed to identify independent risk factors for recurrence. Results: During a mean follow-up of 139 months, 56 patients (5.8%) experienced locoregional recurrence, and 41 (4.3%) developed distant metastasis. Among 35 in-breast recurrences, 14 (40.0%) were ipsilateral and 21 (60.0%) contralateral. Ipsilateral recurrences were more often detected via either MMG or ultrasound alone, whereas contralateral cancers were typically detected through both modalities. During the first postoperative year, all ipsilateral and contralateral recurrences were detected exclusively by ultrasound, with no cancers identified by 6-month MMG (95% CI for 6-month detection: 0–0.38%). Multivariate analysis identified positive axillary lymph node status as the only independent predictor of locoregional recurrence (HR 2.52, 95% CI 1.14–5.54, p = 0.022). Detection patterns showed no significant differences across molecular subtypes (p = 0.665). Conclusions: Annual MMG remains appropriate for breast cancer surveillance in accordance with current guidelines. However, MMG at 6 months post-surgery may be unnecessary, as early detection during the first year was achieved solely by ultrasound. The complementary role of MMG and ultrasound is consistent regardless of molecular subtype. Full article

(This article belongs to the Section Cancer Survivorship and Quality of Life)

17 pages, 1076 KB

Open AccessArticle

Prognostic Factors of IDH Wild-Type Glioblastoma After Extensive Surgery: A Multimodal Atlas of Tumor Locations, Recurrences and Management

by Hajar Selhane, Tiphaine Obara, Guillaume Vogin, René Anxionnat, Guillaume Gauchotte, Luc Taillandier, Marie Blonski and Fabien Rech

Cancers 2026, 18(1), 63; https://doi.org/10.3390/cancers18010063 - 24 Dec 2025

Abstract

Introduction: Glioblastomas have poor prognosis despite aggressive treatment. Patterns of recurrence and overall survival (OS) can be very different. The population with complete resection having a so-called good prognosis can nevertheless present poor OS. Our purpose was to assess the OS and patterns [...] Read more.

Introduction: Glioblastomas have poor prognosis despite aggressive treatment. Patterns of recurrence and overall survival (OS) can be very different. The population with complete resection having a so-called good prognosis can nevertheless present poor OS. Our purpose was to assess the OS and patterns of recurrence thanks to multimodal statistical maps in glioblastoma with large extent of resection (residue < 10 mL). Methods: adult patients presenting IDH wild-type glioblastoma between 2013 and 2019 were selected. Clinical data and MRI characteristics were collected. Preoperative, postoperative, and recurrence volumes were segmented and normalized in the MNI space to compute statistical maps. Log-rank test and Cox model were used to assess OS and prognosis factors. Results: 60 patients were included. Mean residual volume was 0.89 ± 2 mL. Median OS was 22.3 months (95% CI: (20–35)). Initial location in the corpus callosum was associated with low OS (317 vs. 783 days, HR = 0.46, p = 0.003). At recurrence, KPS > 90 and tumor volume < 10 mL were associated with higher OS (p =0.006 and p = 0.05). Tumor contact with the SVZ as well as multifocal recurrence did not show any impact on the OS. Conclusions: High OS can be obtained thanks to surgery with residual volume < 10 mL. Invasion of the corpus callosum at diagnosis is associated with a poor prognosis despite a large extent of resection. Results suggest that large resection near the SVZ might decrease its putative influence on OS. Full article

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

35 pages, 2873 KB

Open AccessArticle

BRG1 (SMARCA4) Status Dictates the Response to EGFR Inhibitors in Wild-Type EGFR Non-Small Cell Lung Cancer

by Rebaz Ahmed, Ranganayaki Muralidharan, Narsireddy Amreddy, Akhil Srivastava, Meghna Mehta, Janani Panneerselvam, Rodrigo Orlandini de Castro, William L. Berry, Susmita Ghosh, Murali Ragothaman, Pawan Acharya, Yan D. Zhao, Roberto Jose Pezza, Anupama Munshi and Rajagopal Ramesh

Cancers 2026, 18(1), 62; https://doi.org/10.3390/cancers18010062 - 24 Dec 2025

Abstract

Background: Epidermal growth factor receptor (EGFR)-targeted tyrosine kinase inhibitors (TKIs) have exhibited efficacy in EGFR-mutant non-small cell lung cancer (NSCLC) patients. However, the response is modest in patients with wild-type (wt)-EGFR, and approximately 30–40% of patients develop TKI resistance. Recently, a role [...] Read more.

Background: Epidermal growth factor receptor (EGFR)-targeted tyrosine kinase inhibitors (TKIs) have exhibited efficacy in EGFR-mutant non-small cell lung cancer (NSCLC) patients. However, the response is modest in patients with wild-type (wt)-EGFR, and approximately 30–40% of patients develop TKI resistance. Recently, a role for BRG1 (SMARCA4) in regulating gene expression and its frequent alteration in various cancers, including NSCLC, has been reported. Yet, its specific function in response to EGFR-TKI therapy remains elusive. Herein, we investigated the role of BRG1 in EGFR-TKI response in vitro and in vivo using lung cancer models. Methods: In vitro, A549, H358, and HCC827 cell lines that varied in their EGFR and BRG1 status were assessed for response to EGFR-TKI upon overexpression or gene silencing of BRG1 through cell viability, cell migration, and Western blotting assays. In vivo, A549 and H358 tumor xenografts that overexpressed BRG1 or had BRG1 silenced were investigated for tumor growth response to EGFR-TKI. Results: EGFRwt/BRG1mt (A549) cells were resistant to TKI, and restoration of wt-BRG1 expression reverted them to TKI sensitivity both in vitro and in vivo. In contrast, silencing of BRG1wt in H358 cells showed a tendency toward TKI resistance. Additionally, wt-EGFR and pAKT^Ser473 protein complex formation in A549 cells was disrupted with an AKT inhibitor (MK2206), resulting in enhanced cytotoxicity in vitro. Conclusions: Our study demonstrates that EGFR-TKI response in wt-EGFR cells is dictated by BRG1 status. These findings propose screening of wt-EGFR NSCLC patients for BRG1 status for identifying individuals likely to benefit from EGFR-TKI therapy versus patients who will benefit from AKT inhibitor treatment. Full article

(This article belongs to the Section Cancer Therapy)

16 pages, 531 KB

Open AccessArticle

Palliative Performance Scale Predicts Survival in Patients with Bone Metastasis Undergoing Radiotherapy

by Gina Hennig, Emma Thrandorf, Dirk Vordermark and Jörg Andreas Müller

Cancers 2026, 18(1), 61; https://doi.org/10.3390/cancers18010061 - 24 Dec 2025

Abstract

Background: Accurate prognostication is essential for clinical decision-making in palliative radiotherapy (RT). The Palliative Performance Scale (PPS) is a validated tool for assessing functional status and estimating survival in palliative care, yet its prognostic value in patients receiving palliative RT for bone metastases [...] Read more.

Background: Accurate prognostication is essential for clinical decision-making in palliative radiotherapy (RT). The Palliative Performance Scale (PPS) is a validated tool for assessing functional status and estimating survival in palliative care, yet its prognostic value in patients receiving palliative RT for bone metastases remains insufficiently explored. This study aimed to evaluate the association between PPS and overall survival (OS) in a real-world cohort of cancer patients undergoing palliative RT. Methods: This retrospective, single-center study included 153 patients who received palliative RT for bone metastases between 2021 and 2025 at the Department of Radiation Oncology, University Hospital Halle (Saale), Germany. Clinical, demographic, and treatment data were extracted from institutional databases. The primary endpoint was OS, defined as the time from the end of RT to death. Univariable and multivariable Cox proportional hazards regression models were used to identify prognostic factors associated with OS, including PPS, sex, age, marital status, BMI, Charlson Comorbidity Index (CCI), and RT completion. Due to violation of the proportional hazards assumption, PPS (<60% vs. ≥60%) was used as a stratification factor in the final Cox model. Logistic regression was performed to explore predictors of discharge to home. Results: The median OS for the entire cohort was 108 days (3.6 months; 95% CI 78–143 days). Male sex (HR 1.61, 95% CI 1.06–2.46, p = 0.027) and older age (HR 0.98, 95% CI 0.96–1.00, p = 0.050) were associated with shorter survival, whereas completion of the prescribed RT course was strongly associated with improved OS (HR 0.06, 95% CI 0.03–0.12, p < 0.001). Patients with PPS ≥60% had significantly better survival compared to those with lower PPS (HR 0.62, 95% CI 0.41–0.93, p = 0.021). After stratification by PPS, no violation of the proportional hazards assumption was detected (global p = 0.55). The stratified model confirmed that male sex, age, and RT completion remained independent predictors of survival. No significant predictors were identified for discharge destination in logistic regression analysis. Conclusions: The PPS is a valuable prognostic tool for patients receiving palliative RT for bone metastases. A PPS of ≥60% was associated with prolonged survival, supporting its use in clinical prognostication and treatment planning. Completion of RT emerged as a strong independent predictor of survival, underscoring the importance of treatment adherence even in palliative settings. Stratification by PPS further improved model validity and prognostic accuracy. Full article

(This article belongs to the Special Issue Radiation Therapy for Metastatic Cancer)

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18 pages, 5319 KB

Open AccessArticle

Automated Baseline-Correction and Signal-Detection Algorithms with Web-Based Implementation for Thermal Liquid Biopsy Data Analysis

by Karl C. Reger, Gabriela Schneider, Keegan T. Line, Alagammai Kaliappan, Robert Buscaglia and Nichola C. Garbett

Cancers 2026, 18(1), 60; https://doi.org/10.3390/cancers18010060 - 24 Dec 2025

Abstract

Background/Objectives: Differential scanning calorimetry (DSC) analysis of blood plasma, also known as thermal liquid biopsy (TLB), is a promising approach for disease detection and monitoring; however, its wider adoption in clinical settings has been hindered by labor-intensive data processing workflows, particularly baseline correction. [...] Read more.

Background/Objectives: Differential scanning calorimetry (DSC) analysis of blood plasma, also known as thermal liquid biopsy (TLB), is a promising approach for disease detection and monitoring; however, its wider adoption in clinical settings has been hindered by labor-intensive data processing workflows, particularly baseline correction. Methods: We developed and tested two automated algorithms to address critical bottlenecks in TLB analysis: (1) a baseline-correction algorithm utilizing rolling-variance analysis for endpoint detection, and (2) a signal-detection algorithm that applies auto-regressive integrated moving average (ARIMA)-based stationarity testing to determine whether a profile contains interpretable thermal features. Both algorithms are implemented in ThermogramForge, an open-source R Shiny web application providing an end-to-end workflow for data upload, processing, and report generation. Results: The baseline-correction algorithm demonstrated excellent performance on plasma TLB data (characterized by high heat capacity), matching the quality of rigorous manual processing. However, its performance was less robust for low signal biofluids, such as urine, where weak thermal transitions reduce the reliability of baseline estimation. To address this, a complementary signal-detection algorithm was developed to screen for TLB profiles with discernable thermal transitions prior to baseline correction, enabling users to exclude non-informative data. The signal-detection algorithm achieved near-perfect classification accuracy for TLB profiles with well-defined thermal transitions and maintained a low false-positive rate of 3.1% for true noise profiles, with expected lower performance for borderline cases. The interactive review interface in ThermogramForge further supports quality control and expert refinement. Conclusions: The automated baseline-correction and signal-detection algorithms, together with their web-based implementation, substantially reduce analysis time while maintaining quality, supporting more efficient and reproducible TLB research. Full article

(This article belongs to the Special Issue Thermal Analysis and Proteomic Approaches for Biofluid Proteome Profiling in Cancer Diagnostics)

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17 pages, 7824 KB

Open AccessReview

Freeze the Disease: Advances the Therapy for Barrett’s Esophagus and Esophageal Adenocarcinoma

by Ted G. Xiao, Shree Atul Patel, Nishita Sunkara and Virendra Joshi

Cancers 2026, 18(1), 59; https://doi.org/10.3390/cancers18010059 - 24 Dec 2025

Abstract

Cryotherapy involves flash freezing of tissue and removing unwanted tissue. Mechanism of injury is causing cell membrane rupture by rapid multiple freeze–thaw cycles, while reserving tissue architecture and the collagen matrix. This promotes favorable wound healing. In recent years, it has gained increasing [...] Read more.

Cryotherapy involves flash freezing of tissue and removing unwanted tissue. Mechanism of injury is causing cell membrane rupture by rapid multiple freeze–thaw cycles, while reserving tissue architecture and the collagen matrix. This promotes favorable wound healing. In recent years, it has gained increasing attention as a treatment option for upper gastrointestinal diseases (Barrett’s Esophagus and early cancer). Currently, two FDA-approved delivery methods are available in the GI tract: Cryoballoon and spray cryotherapy, which will be discussed. In this review, we also propose to examine the expanding role of cryotherapy in gastrointestinal practice, drawing from both clinical studies and illustrative vignettes. In addition, we will highlight its established role in eradicating Barrett’s with low and high-grade dysplasia and compare its outcomes and safety profile with radiofrequency ablation (RFA). We will also discuss the application and safety of spray cryotherapy in the palliation of malignant esophageal strictures when compared with Esophageal stent placement. Cryotherapy may have immunological potential, and it may shrink both primary and metastatic diseases. Ongoing research in this field of Cryo-immunology will be highlighted. Beyond esophageal neoplasia, cryotherapy is increasingly utilized in other upper gastrointestinal precancerous conditions. Through this synthesis, our goal is to provide a timely and comprehensive overview of advancements in cryotherapy and its potential to reshape novel therapeutic approaches in upper gastrointestinal cancers. Finally, we highlight the evolution of a novel platform using nitrous oxide delivered by a handheld device, a contact balloon, and a small replaceable cartridge. This approach may make delivery of cryogen application favorable and a first-line approach in the management of Barrett’s esophagus and early cancer. In addition, Cryoballoon therapy for dysphagia palliation for malignant esophageal strictures may become a preferred approach as more data evolves. Full article

(This article belongs to the Special Issue New Insights in Esophageal Cancer Diagnosis and Treatment)

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18 pages, 2939 KB

Open AccessSystematic Review

New Insights into Prostate Cancer Susceptibility in European Caucasians: A Systematic Review and Meta-Analysis of CYP3A4 Pharmacogene

by Maria Pagoni, Claudia Cava, George T. Tsangaris, Fotios Siannis and Nikolaos Drakoulis

Cancers 2026, 18(1), 58; https://doi.org/10.3390/cancers18010058 - 24 Dec 2025

Abstract

Background/Objectives: Prostate cancer is the most frequent male malignancy. The incidence of disease varies among different ethnic groups. CYP3A polymorphisms are candidates for prostate cancer susceptibility studies. The aim of the present study is to investigate the ethnicity-related clinical impact of CYP3A4 variants [...] Read more.

Background/Objectives: Prostate cancer is the most frequent male malignancy. The incidence of disease varies among different ethnic groups. CYP3A polymorphisms are candidates for prostate cancer susceptibility studies. The aim of the present study is to investigate the ethnicity-related clinical impact of CYP3A4 variants on prostate cancer risk. Methods: A systematic literature search and meta-analysis were conducted according to PRISMA guidelines. A total of 10 eligible studies, including 3116 prostate cancer cases and 3008 healthy controls, were analyzed. We evaluated the association between the CYP3A4*1B (rs2740574, −392 A > G) variant and prostate cancer risk in European Caucasians. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using six genetic models. Data were analyzed using fixed and random-effects models based on the I2 value of heterogeneity magnitude. Funnel plots and Egger’s linear regression tests were used to assess publication bias. Results: CYP3A4*1B was associated with prostate cancer susceptibility in the allele (G vs. A: OR = 1.32, CI = 0.91–1.93), dominant (AG + GG vs. AA OR = 1.41, CI = 0.95–2.09), recessive (GG vs. AA + AG, OR = 1.82, CI = 1.26–2.63), homozygous (GG vs. AA, OR = 1.92, CI = 1.32–2.77), heterozygous model (AG vs. AA, OR = 1.31, CI = 0.89–1.93) and co-dominant model (AG vs. AA + GG; OR = 1.27, CI = 0.88–1.85). Significant heterogeneity characterized the allele, as well as the dominant model (I2 = 84.1%, I2 = 80.0%). Egger’s tests (p < 0.05) and funnel plots did not identify publication bias. Conclusions: The present meta-analysis indicates that the G allele and GG genotype might affect prostate cancer susceptibility in European Caucasians; however, the validity and reliability of the results need to be examined in future research. Full article

(This article belongs to the Special Issue Cancer Genomics: Interpreting the Changing Landscape in Cancer Diagnosis and Treatment (2nd Edition))

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17 pages, 452 KB

Open AccessReview

Clear Cell Renal Cell Carcinoma Metastasis to the Thyroid: A Narrative Review of the Literature

by Menelaos G. Samaras, Abraham Pouliakis, Konstantinos Skaretzos, Ioannis Boutas, Adamantia Kontogeorgi, Dionysios T. Dimas, Argyro-Ioanna Ieronimaki, Magda Zanelli, Andrea Palicelli, Maurizio Zizzo, Giuseppe Broggi, Rosario Caltabiano, Serena Salzano and Nektarios I. Koufopoulos

Cancers 2026, 18(1), 57; https://doi.org/10.3390/cancers18010057 (registering DOI) - 24 Dec 2025

Abstract

Clear cell renal cell carcinoma is the most common histological type of renal cancer, which is a common cancer type usually associated with a long clinical course. During this course, various metastatic sites can be observed. In this review, we have focused on [...] Read more.

Clear cell renal cell carcinoma is the most common histological type of renal cancer, which is a common cancer type usually associated with a long clinical course. During this course, various metastatic sites can be observed. In this review, we have focused on metastases to the thyroid gland. We conducted research in three medical databases, including PubMed, Scopus, and Web of Science, using the same search algorithm. Our inclusion criteria focused on case reports and case series studies since 2011, covering therapeutic strategies for the primary and/or metastatic disease, as well as subsequent follow-up data. Studies with insufficient or uncertain data, or written in a language other than English, were excluded. An analysis of 510 articles from PubMed, 1729 from Scopus, and 649 from Web of Science, after application of inclusion and exclusion criteria, resulted in 77 reports, analyzing 189 patients. A description of the clinical, pathological, ancillary, and follow-up data, in the light of recent therapeutic schemes, was attempted. Our results suggest that metastases’ imaging features comprised more commonly a solitary nodule with a median size of 3.5 cm and worrisome features in ultrasonography, such as heterogeneity, hypoechogenicity, partially solid configuration, and variable internal vascularization. Histological and immunohistochemical examination of the lesion is necessary because these findings are not specific. Common non-thyroid metastases are seen in the urogenital system, lungs, and pancreas. We calculated the restricted mean survival from primary diagnosis at 274.6 months (95% CI: 264.3–285.0 months) and the restricted mean survival from thyroid metastases treatment at 93.9 months (95% CI: 65.3–122.4 months). Results regarding how patient characteristics affect these survival numbers were statistically nonsignificant (p > 0.05). Full article

(This article belongs to the Section Cancer Metastasis)

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12 pages, 2110 KB

Open AccessReview

Detection of Human Papillomavirus (HPV) in HPV-Associated Oropharyngeal Squamous Cell Carcinoma: A Review of Diagnostic Approach and Its Importance for the Head and Neck Oncologist

by Amanda J. Bastien, Daniel Manzoor, Evan S. Walgama, Kevin S. Scher, Julie K. Jang, Justin Moyers, Zachary S. Zumsteg, Allen S. Ho and Jon Mallen-St. Clair

Cancers 2026, 18(1), 56; https://doi.org/10.3390/cancers18010056 - 24 Dec 2025

Abstract

Introduction: Histopathologic assessment of surgical specimens imparts crucial information that is essential for diagnosis, treatment planning and prognostication for patients with Oropharyngeal Squamous Cell Carcinoma (OPSCC). This review explores the range of diagnostic techniques utilized to assess the HPV (Human Papilloma Virus) status [...] Read more.

Introduction: Histopathologic assessment of surgical specimens imparts crucial information that is essential for diagnosis, treatment planning and prognostication for patients with Oropharyngeal Squamous Cell Carcinoma (OPSCC). This review explores the range of diagnostic techniques utilized to assess the HPV (Human Papilloma Virus) status in OPSCC. It covers both traditional methods—such as p16 immunohistochemistry, HPV in situ hybridization, and DNA polymerase chain reaction (PCR)—and newer, evolving strategies including circulating HPV tumor DNA analysis and oral HPV DNA/mRNA PCR testing. Discussion: There are currently several histopathologic techniques for the diagnosis of HPV-associated OPSCC. This complexity of care has led to guidelines from numerous authorities (NCCN, ASCO, CAP), which this paper discusses and summarizes for head and neck oncology specialists. Conclusion: The ability to detect HPV in HPV-associated OPSCC is imperative for diagnosis, prognostication, staging, and management of the disease. Advances including liquid biopsy (TTMV-HPV DNA) may be utilized as an adjunct to diagnosis, treatment, and cancer surveillance in the future. Full article

(This article belongs to the Special Issue Advances in the Management of Oropharyngeal Cancer: Navigating the HPV-Associated Landscape)

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14 pages, 282 KB

Open AccessReview

The Role of Organ Sparing Approaches After Total Neoadjuvant Treatment in Rectal Cancer

by Gianluca Rizzo, Vincenzo Tondolo, Luca Emanuele Amodio, Federica Marzi, Camilla Marandola, Donato Paolo Pafundi, Giuseppe De Rito and Claudio Coco

Cancers 2026, 18(1), 55; https://doi.org/10.3390/cancers18010055 - 24 Dec 2025

Abstract

Organ-preserving strategies have gained increasing relevance in the management of rectal cancer, driven by the improved ability of neoadjuvant therapies to induce major and complete tumor regression. The introduction of Total Neoadjuvant Therapy (TNT), delivered through induction and/or consolidation chemotherapy combined with radiotherapy, [...] Read more.

Organ-preserving strategies have gained increasing relevance in the management of rectal cancer, driven by the improved ability of neoadjuvant therapies to induce major and complete tumor regression. The introduction of Total Neoadjuvant Therapy (TNT), delivered through induction and/or consolidation chemotherapy combined with radiotherapy, has substantially increased both pathological and clinical complete response rates. This progress has renewed interest in non-operative management—namely Watch-and-Wait (W&W)—and in local excision (LE) as potential alternatives to total mesorectal excision (TME). However, the W&W strategy raises important oncologic concerns, including a non-negligible rate of local regrowth—consistently reported at approximately 20–30%—which is associated with inferior distant metastasis-free survival and overall survival. These limitations underscore the inherent uncertainty in reliably defining a true clinical complete response. Within this context, LE may serve as a valuable diagnostic and therapeutic modality by confirming the pathological response, improving local control through removal of residual resistant tumor clones, and enabling more accurate stratification of patients suitable for organ preservation versus those requiring completion TME. Overall, while TNT has expanded the therapeutic opportunities for rectal preservation, LE appears to play a critical role in reducing the discordance between clinical and pathological assessment, thereby offering a more oncologically secure pathway toward organ preservation. This narrative review discusses the current role, benefits, and limitations of organ-preserving approaches after TNT in both locally advanced and early rectal cancer. Full article

(This article belongs to the Special Issue The Advance of Clinical Therapy and Prognosis in Gastrointestinal Cancer)

20 pages, 505 KB

Open AccessReview

Expression and Clinical Significance of CD47 in Colorectal Cancer: A Review

by Qijie Li, Paola Vignali, Donghao Tang, Giulia Martinelli, Beatrice Fuochi, Rebecca Sparavelli, Anello Marcello Poma, Rossella Bruno, Elisabetta Macerola and Clara Ugolini

Cancers 2026, 18(1), 54; https://doi.org/10.3390/cancers18010054 - 24 Dec 2025

Abstract

Cluster of Differentiation 47 (CD47), an innate immune checkpoint, facilitates immune escape by binding signal regulatory protein alpha (SIRPα) to inhibit macrophage phagocytosis. Its significance in colorectal cancer (CRC) has garnered heightened interest. This review summarizes five immunohistochemistry (IHC) studies and complementary transcriptomic [...] Read more.

Cluster of Differentiation 47 (CD47), an innate immune checkpoint, facilitates immune escape by binding signal regulatory protein alpha (SIRPα) to inhibit macrophage phagocytosis. Its significance in colorectal cancer (CRC) has garnered heightened interest. This review summarizes five immunohistochemistry (IHC) studies and complementary transcriptomic analyses assessing CD47 in CRC. IHC results consistently indicated membrane overexpression, though positivity rates varied widely (16–91%) due to methodological heterogeneity. Transcriptomic results confirmed CD47 upregulation, especially in Consensus Molecular Subtype 1 (CMS1) and CMS4 subtypes and revealed co-expression with immune checkpoints and oncogenic pathways. Clinically, high CD47 levels were associated with advanced TNM stage, metastasis, poor differentiation, and altered immune infiltration; however, the prognostic significance varied among cohorts. Overall, CD47 appears to be a promising biomarker and therapeutic target, but clinical translation requires standardized evaluation, including harmonized antibody selection and scoring cut-offs, and prospective validation. Full article

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

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16 pages, 7433 KB

Open AccessArticle

Two Decades of Real-World Study in Newly Diagnosed Multiple Myeloma: Evolving Treatment and Outcomes in China with Reference to the United States

by Jingyu Xu, Meng Shu, Hsingwen Chung, Jian Cui, Yuntong Liu, Wenqiang Yan, Qirui Bai, Ning Dai, Lingna Li, Jieqiong Zhou, Yating Li, Chenxing Du, Shuhui Deng, Weiwei Sui, Yan Xu, Hong Qiu, Lugui Qiu and Gang An

Cancers 2026, 18(1), 53; https://doi.org/10.3390/cancers18010053 - 24 Dec 2025

Abstract

Background: The survival of newly diagnosed multiple myeloma (NDMM) has improved markedly worldwide with the introduction of proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), and anti-CD38 monoclonal antibodies. However, real-world progress among Chinese patients remains underexplored. This study evaluated 20-year survival trends in [...] Read more.

Background: The survival of newly diagnosed multiple myeloma (NDMM) has improved markedly worldwide with the introduction of proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), and anti-CD38 monoclonal antibodies. However, real-world progress among Chinese patients remains underexplored. This study evaluated 20-year survival trends in patients with NDMM treated in our institute and benchmarked them against outcomes from the Flatiron Health database in the United States. Patients and methods: Consecutive adults diagnosed with NDMM in our institute between 2003 and 2023 were retrospectively analyzed. U.S. patients were identified from the Flatiron Health database using similar inclusion criteria. Clinical characteristics, first-line regimens, and autologous stem cell transplantation (ASCT) rates were summarized. Overall survival (OS) and progression-free survival (PFS) were estimated by Kaplan–Meier methods. Results: Among 1622 Chinese and 12,582 US patients, median age was 57 vs. 68 years. The median PFS and OS of NDMM patients in our institute was 40.1 months and 99.6 months, respectively. Induction therapy in the NICHE cohort changed markedly from primarily chemo-based therapy to combined PIs + IMIDs-based treatment, whereas these treatments were used much earlier in Flatiron. Uptake of new therapies in China increased rapidly after their inclusion in national health insurance. ASCT utilization was higher overall in China (34.9% vs. 22.1%) but remained lower among patients >65 years (6.7% vs. 12.1%). Conclusions: Two decades of real-world data from a major Chinese myeloma center demonstrate substantial improvements in survival and modernization of NDMM treatment, while highlighting persistent disparities amongst older adults. Full article

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

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21 pages, 5861 KB

Open AccessArticle

Integrative Transcriptomic and Perturbagen Analyses Reveal Sex-Specific Molecular Signatures Across Glioma Subtypes

by Madhu Vishnu Sankar Reddy Rami Reddy, Jacob F. Wood, Jordan Norris, Kathryn Becker, Shawn C. Murphy, Sishir Doddi, Ali Imami, William G. Ryan V, Jennifer Nguyen, Jason Schroeder, Kathryn Eisenmann and Robert E. McCullumsmith

Cancers 2026, 18(1), 52; https://doi.org/10.3390/cancers18010052 - 24 Dec 2025

Abstract

Background: Emerging evidence suggests that biological sex shapes glioma biology and therapeutic response. Methods: We performed a sex-stratified analysis of CGGA (Chinese Glioma Genome Atlas) RNA sequencing data comparing low-grade glioma (LGG) with high-grade glioma (HGG) and glioblastoma (GBM). Using the [...] Read more.

Background: Emerging evidence suggests that biological sex shapes glioma biology and therapeutic response. Methods: We performed a sex-stratified analysis of CGGA (Chinese Glioma Genome Atlas) RNA sequencing data comparing low-grade glioma (LGG) with high-grade glioma (HGG) and glioblastoma (GBM). Using the 3PodR framework, we integrated differential expression analysis with Gene Set Enrichment Analysis (GSEA), EnrichR, leading-edge analysis, and iLINCS drug repurposing. Results: These comparisons provide a proxy for biological processes underlying malignant transformation. In LGG vs. HGG, 973 significantly differentially expressed genes (DEGs) were identified in females and 1236 in males, with 15.5% and 33.5% unique to each sex, respectively. In LGG vs. GBM, 2011 DEGs were identified in females and 2537 in males, with 12.6% and 30.7% being unique. Gene-level contrasts included GLI1 upregulation in males and downregulation in females, GCGR upregulation in males, MYOD1 upregulation in females, and HIST1H2BH downregulation in males. Additional top DEGs included PRLHR, DGKK, DNMBP-AS1, HOXA9, CTB-1I21.1, RP11-47I22.1, HPSE2, SAA1, DLK1, H19, PLA2G2A, and PI3. In both sexes, LGG–HGG and LGG–GBM grade comparisons converged on neuronal and synaptic programs, with enrichment of glutamatergic receptor genes and postsynaptic modules, including GRIN2B, GRIN2A, GRIN2C, GRIN1, and CHRNA7. In contrast, collateral pathways diverged by sex: females showed downregulation of mitotic and chromosome-segregation programs, whereas males showed reduction of extracellular matrix and immune-interaction pathways. Perturbagen analysis nominated signature-reversing compounds across sexes, including histone deacetylase inhibitors, Aurora kinase inhibitors, microtubule-targeting agents such as vindesine, and multi-kinase inhibitors targeting VEGFR, PDGFR, FLT3, PI3K, and MTOR. Conclusions: Glioma grade comparisons reveal a shared neuronal–synaptic program accompanied by sex-specific transcriptional remodeling. These findings support sex-aware therapeutic strategies that pair modulation of neuron–glioma coupling with chromatin- or receptor tyrosine kinase/angiogenic-targeted agents, and they nominate biomarkers such as GLI1, MYOD1, GCGR, PRLHR, and HIST1H2BH for near-term validation. Full article

(This article belongs to the Special Issue Molecular Pathology of Brain Tumors)

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14 pages, 6455 KB

Open AccessReview

Molecular Classification of Endometrial Carcinomas: Review and Recent Updates

by Anita Kumari, Himani Kumar, Samuel E. Harvey, Deyin Xing and Zaibo Li

Cancers 2026, 18(1), 51; https://doi.org/10.3390/cancers18010051 - 24 Dec 2025

Abstract

Endometrial carcinoma (EC) continues to represent a major cause of gynecologic cancer–related mortality among women worldwide. Its multifactorial etiopathogenesis and underlying molecular heterogeneity have been the focus of extensive investigation. While traditional histological classification provides essential diagnostic insight, it is limited in predicting [...] Read more.

Endometrial carcinoma (EC) continues to represent a major cause of gynecologic cancer–related mortality among women worldwide. Its multifactorial etiopathogenesis and underlying molecular heterogeneity have been the focus of extensive investigation. While traditional histological classification provides essential diagnostic insight, it is limited in predicting prognosis and therapeutic response due to significant interobserver variability. Recent advances in molecular biology and cancer genomics have profoundly enhanced understanding of EC pathogenesis. The Cancer Genome Atlas (TCGA) project delineated four distinct molecular subtypes of EC, POLE ultra-mutated, microsatellite instability hypermutated (MSI-H), copy number low (CNL) and copy number high (CNH), each defined by unique genomic alterations, histopathologic features, and clinical behaviors. These molecular groups demonstrate significant prognostic and therapeutic implications, correlating with differential outcomes and treatment responses. This review summarizes current evidence on the genomic landscape of endometrial carcinoma and underscores the pivotal role of molecular classification in improving diagnostic accuracy, prognostic stratification, and personalized therapy. Ongoing research into molecular biomarkers holds promise for refining patient management and optimizing clinical outcomes. Full article

(This article belongs to the Special Issue The Genomic Landscape of Gynecological Cancers)

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13 pages, 997 KB

Open AccessReview

A Review of the Pathological and Molecular Diagnosis of Primary Myelofibrosis

by Richard Shao, Christopher Ryder, Le Wang, Hailing Zhang, Lynn Moscinski, Michael Martin, Mac Shebes, Julie Y. Li and Jinming Song

Cancers 2026, 18(1), 50; https://doi.org/10.3390/cancers18010050 - 24 Dec 2025

Abstract

Primary myelofibrosis (PMF) is a Philadelphia chromosome (Ph)-negative myeloproliferative neoplasm (MPN) that features clonal proliferation of atypical megakaryocytes and myeloid cells, fibrosis of the bone marrow, extramedullary hematopoiesis, and increased risk of leukemic transformation to acute myeloid leukemia (AML). With the widespread application [...] Read more.

Primary myelofibrosis (PMF) is a Philadelphia chromosome (Ph)-negative myeloproliferative neoplasm (MPN) that features clonal proliferation of atypical megakaryocytes and myeloid cells, fibrosis of the bone marrow, extramedullary hematopoiesis, and increased risk of leukemic transformation to acute myeloid leukemia (AML). With the widespread application of molecular studies, especially next generation sequencing (NGS), significant advances have reshaped our understanding of the molecular pathogenesis of PMF and the prognostic relevance of specific gene mutations. In this review, we summarize its clinicopathologic features, genetic and molecular findings, updated diagnostic criteria, and differential diagnosis. These updates have been incorporated into the 5th edition of the World Health Organization classification of Hematolymphoid Tumors (WHO-5th) and the 2022 International Consensus Classification (ICC), thereby improving diagnostic accuracy and risk stratification, both of which are essential for tailoring treatment strategies and enhancing patient outcomes. Full article

(This article belongs to the Special Issue Molecular and Genetic Diagnosis and Targeted Therapy of Myeloproliferative Neoplasms (2nd Edition))

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15 pages, 1065 KB

Open AccessArticle

Central Adiposity, Obesity, Metabolic Syndrome, and the Risk of Thyroid Cancer in Adults Aged ≥75 Years: A Nationwide Korean Cohort Study

by Kyung Do Han, Kwan Hoon Jo, Yunjung Cho, Hyuk-Sang Kwon, Je-Ho Han, Sung-Dae Moon and Eun Sook Kim

Cancers 2026, 18(1), 49; https://doi.org/10.3390/cancers18010049 - 24 Dec 2025

Abstract

Background: The contribution of adiposity and metabolic syndrome (MetS) to thyroid cancer risk in late life, particularly among the elderly, is unclear. Methods: We conducted a nationwide cohort study of Korean adults aged ≥75 years who underwent standardized health screening. Exposures [...] Read more.

Background: The contribution of adiposity and metabolic syndrome (MetS) to thyroid cancer risk in late life, particularly among the elderly, is unclear. Methods: We conducted a nationwide cohort study of Korean adults aged ≥75 years who underwent standardized health screening. Exposures were body mass index (BMI), waist circumference (WC), and MetS defined by standard clinical criteria. The incidence of thyroid cancer was determined using administrative data. Fine–Gray sub-distribution hazard models estimated adjusted hazard ratios (HRs) with prespecified stratification by sex and age (75–84 vs. ≥85 years). Results: Among 1,164,707 participants (60.3% women), 2645 incident cases were identified. In the fully adjusted models, obesity (BMI ≥ 25 kg/m²) was associated with a 37% higher hazard (HR, 1.37; 95% confidence interval [CI], 1.27–1.49) and MetS with an 18% higher hazard (HR, 1.18; 95% CI, 1.09–1.28). In sex-stratified models, MetS was associated with thyroid cancer in women (HR 1.19; 95% CI, 1.08–1.31) and showed a similar direction of association in men (HR 1.16; 95% CI, 1.00–1.35), with overlapping CIs. By age, associations were evident at 75–84 years (MetS: HR, 1.18; obesity: HR, 1.36), whereas at ≥85 years, only obesity remained significant (HR, 1.90; 95% CI, 1.13–3.18). Among MetS components, high WC showed the most consistent association (HR, 1.31; 95% CI, 1.21–1.42). Conclusions: In adults aged ≥75 years, general obesity and, in particular, central adiposity are robustly associated with incident thyroid cancer, whereas metabolic syndrome confers a more modest and mainly age- and sex-specific additional risk. Full article

(This article belongs to the Special Issue Evolving Understanding of the Epidemiology of Thyroid Cancer)

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18 pages, 2012 KB

Open AccessArticle

Fab Antibody Fragments to Dog Leukocyte Antigen DR (DLA-DR) Directly Suppress Canine Lymphoma Cell Line Growth In Vitro and in Murine Xenotransplant Model

by Aleksandra Studzińska, Marek Pieczka, Angelika Kruszyńska, Leszek Moniakowski, Anna Urbaniak, Andrzej Rapak and Arkadiusz Miazek

Cancers 2026, 18(1), 48; https://doi.org/10.3390/cancers18010048 - 23 Dec 2025

Abstract

Background/Objectives: Canine Diffuse Large B-cell Lymphoma (cDLBCL) is characterized by a high prevalence of MHC II DR (DLA-DR) antigen overexpression. Murine anti-pan-DLA-DR monoclonal antibodies (mAbs) B5 and E11 have been previously observed to promote death of cDLBCL cells in vitro and in vivo. [...] Read more.

Background/Objectives: Canine Diffuse Large B-cell Lymphoma (cDLBCL) is characterized by a high prevalence of MHC II DR (DLA-DR) antigen overexpression. Murine anti-pan-DLA-DR monoclonal antibodies (mAbs) B5 and E11 have been previously observed to promote death of cDLBCL cells in vitro and in vivo. Consequently, DLA-DR antigens are considered a prospective target for passive immunotherapy aside from CD20. While infusion of anti-pan MHC II mAbs has demonstrated tumor suppression in cDLBCL xenografted immunodeficient mice, the relative contributions of direct cellular versus immune-mediated mechanisms to this therapeutic effect remain undefined. This study aimed to dissect these potential mechanisms of mAb E11. Methods: Canine lymphoma and leukemia cell lines CLBL1 and CLB70 were incubated with full E11 antibody or its F(ab′)2 and Fab fragments and cell viability was assessed with sub-G1 assay then, NOD-SCID mice were xenotransplanted with 1.5 × 10⁷ canine CLBL1 cells expressing nanoluciferase and were infused either with mAb E11 or its fragments, each at 1 mg/kg body mass, twice weekly for three consecutive weeks. Tumor burden was monitored by assessing body weight, nanoluciferase activity in blood, and by flow cytometric analyses of bone marrow tumor cell content. Time to tumor progression (TTP) was calculated based on weight loss and luminescence measurements. Results: We observed cytotoxic activity of monovalent E11-Fab fragments in vitro and in vivo. The mean TTP for mice treated with irrelevant mouse IgG antibodies was 9.8 ± 4.65 days. In contrast, treatment with E11 Fab fragments resulted in a TTP of 19.1 ± 2.67 days, which was similar to that achieved with the full E11 mAb (19.5 ± 1.73 days) and E11 F(ab′)2 fragments (18.1 ± 2.9 days). Conclusions: Our findings demonstrate a potent antibody cytotoxicity mechanism that operates in vivo and is independent of cell surface MHC II crosslinking or Fc engagement. These data support the promising potential of E11-Fab fragments for further clinical development as a therapeutic agent in canine lymphoma. Full article

(This article belongs to the Special Issue Advances in B-Cell Lymphoma: From Diagnostics to Cure)

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13 pages, 1584 KB

Open AccessArticle

Beyond Survival: Understanding Ethnic and Socioeconomic Disparities in Post-Cancer Healthcare Use in England

by Tahania Ahmad, Abu Z. M. Dayem Ullah, Claude Chelala and Stephanie J. C. Taylor

Cancers 2026, 18(1), 47; https://doi.org/10.3390/cancers18010047 - 23 Dec 2025

Abstract

Background: Cancer survivors represent a growing proportion of the UK population and often experience higher multimorbidity and healthcare needs. However, limited research in the UK has explored ethnic and socioeconomic disparities in healthcare resource use among long-term cancer survivors. Methods: Using linked primary [...] Read more.

Background: Cancer survivors represent a growing proportion of the UK population and often experience higher multimorbidity and healthcare needs. However, limited research in the UK has explored ethnic and socioeconomic disparities in healthcare resource use among long-term cancer survivors. Methods: Using linked primary care (Clinical Practice Research Data) and secondary care (Hospital Episode Statistics–Admitted Patient Care) data between 2010 and 2020, this population-based cohort study compared healthcare utilisation among 170,352 cancer survivors and 415,975 matched controls without a cancer diagnosis. Outcomes included primary care consultations and hospital admissions (planned and emergency). Analyses adjusted for age, sex, body mass index, smoking, ethnicity, and the Index of Multiple Deprivation. Negative binomial models were used to estimate incidence rate ratios (IRRs). Results: Cancer survivors averaged 33 more primary-care consultations over ten years than controls, with Pakistani, Indian, and White survivors recording the higher rates. Hospital admissions were consistently higher among survivors across all age groups, peaking in those aged 60–75 years. Planned admissions were highest among Black Caribbean (IRR 1.80 (95% CI 1.73–1.87)), Pakistani (IRR 1.71 (1.63–1.78)), and Bangladeshi (IRR 1.66 (1.53–1.80)) groups. Emergency admissions followed a similar trend, remaining statistically significant only for Pakistani survivors (IRR 1.23 (1.16–1.30)). A strong socioeconomic gradient was observed, with healthcare utilisation increasing as deprivation worsened. Conclusions: Cancer survivors experience substantially greater healthcare use than matched controls, with persistent ethnic and socioeconomic disparities. Strategies to reduce disparities should focus on earlier diagnosis, enhanced long-term care coordination, and culturally informed interventions addressing both cancer survivorship and multimorbidity. Full article

(This article belongs to the Section Cancer Survivorship and Quality of Life)

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