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Issue 9
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Cancers, Volume 17, Issue 9 (May-1 2025) – 213 articles

Cover Story (view full-size image): This study uses ANOVA to explore how deep learning model parameters influence breast cancer classification. By applying attention mechanisms, the model not only classifies images but also identifies critical regions, improving interpretability. Our findings provide insights into the key factors affecting model performance, making AI tools more transparent and reliable for clinical use. View this paper
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14 pages, 3031 KiB  
Article
Natural Language Processing of Radiology Reports to Assess Survival in Patients with Advanced Melanoma
by Jeeban P. Das, Jordan Eichholz, Varadan Sevilimedu, Natalie Gangai, Danny N. Khalil, Michael A. Postow and Richard K. G. Do
Cancers 2025, 17(9), 1595; https://doi.org/10.3390/cancers17091595 - 7 May 2025
Viewed by 191
Abstract
Background/Objectives: To use natural language processing (NLP) to extract large-scale data from the CT radiology reports of patients with advanced melanoma treated with immunotherapy and to determine whether liver metastases affect survival. Methods: Patient criteria (M1 disease subclassified into M1a, M1b, [...] Read more.
Background/Objectives: To use natural language processing (NLP) to extract large-scale data from the CT radiology reports of patients with advanced melanoma treated with immunotherapy and to determine whether liver metastases affect survival. Methods: Patient criteria (M1 disease subclassified into M1a, M1b, or M1c) as well as alternative criteria (M1 with advanced melanoma, imaged with CT chest, abdomen, and pelvis from July 2014–March 2019) were included retrospectively. NLP was used to identify metastases from CT reports, and then patients were classified according to American Joint Committee on Cancer (AJCC) staging disease subclassified into M1L+ or M1L−, indicating whether liver metastases were present or not). Statistical analysis included constructing Kaplan–Meier survival curves and calculating hazard ratios (HRs). Results: 2239 patients were included (mean age, 63 years). Whether using AJCC or alternative criteria, overall survival (OS) was poorest for M1L+ (entire cohort median OS, 0.69 years [95% CI: 0.60–0.82]; immunotherapy cohort median OS, 1.4 years [95% CI: 0.92–2.0]) compared to M1L− (entire cohort median OS, 1.8 years [95% CI: 1.4–2.2]; immunotherapy cohort median OS; M1L−, 2.9 years [95% CI: 2.3–3.9]). The median HR for M1L+ (median HR, 5.35 [95% CI: 4.59–6.24]) was higher than that for M0 (p < 0.001). The median HR for M1L+ (median HR, 2.13 [95% CI: 1.65–2.64]) was higher than that for M0 (p < 0.01). Conclusions: Patients with advanced melanoma, particularly those with liver metastases, demonstrated inferior survival, even when treated with immunotherapy. Full article
(This article belongs to the Special Issue Enhancing Precision in Cancer Treatment: AI-Driven Innovations in Imaging)
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14 pages, 576 KiB  
Review
Immune Checkpoint Inhibitors and Antibody-Drug Conjugates in Urothelial Carcinoma: Current Landscape and Future Directions
by Shugo Yajima and Hitoshi Masuda
Cancers 2025, 17(9), 1594; https://doi.org/10.3390/cancers17091594 - 7 May 2025
Viewed by 354
Abstract
Background/Objectives: Urothelial carcinoma (UC) treatment has been transformed by immunotherapy and antibody-drug conjugates (ADCs). This review evaluates the current evidence for these approaches and identifies future directions. Methods: We conducted a structured review of clinical trials, meta-analyses, and guidelines published until early 2025. [...] Read more.
Background/Objectives: Urothelial carcinoma (UC) treatment has been transformed by immunotherapy and antibody-drug conjugates (ADCs). This review evaluates the current evidence for these approaches and identifies future directions. Methods: We conducted a structured review of clinical trials, meta-analyses, and guidelines published until early 2025. Results: Immune checkpoint inhibitors have established benefits across multiple settings: post-platinum therapy (pembrolizumab, nivolumab), maintenance therapy (avelumab), adjuvant settings for high-risk muscle-invasive disease (nivolumab), and BCG-unresponsive non-muscle-invasive disease (pembrolizumab). Enfortumab vedotin (targeting Nectin-4) has proven effective in post-platinum/post-immunotherapy. Most significantly, enfortumab vedotin plus pembrolizumab has redefined first-line treatment with unprecedented survival benefits (median OS 31.5 months vs. 16.1 months with chemotherapy; HR 0.47), and nivolumab plus gemcitabine-cisplatin improved outcomes in cisplatin-eligible patients. Key challenges include managing unique toxicity profiles, optimizing treatment sequencing, and developing reliable biomarkers. Conclusions: Combination approaches offer the most promising path forward, with future research needed on resistance mechanisms, biomarker development, and expanding these therapies to earlier disease stages. Full article
(This article belongs to the Special Issue Immunotherapy in Urothelial Carcinoma)
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11 pages, 1665 KiB  
Article
Survival Benefits of GLP-1 Receptor Agonists in Patients with Neuroendocrine Neoplasms: A Large-Scale Propensity-Matched Cohort Study
by Manal S. Fawzy, Awwad Alenezy, Jessan A. Jishu, Issa Khan, Ahmad Dessouky, Ahmed Abdelmaksoud, Kristen E. Limbach and Eman A. Toraih
Cancers 2025, 17(9), 1593; https://doi.org/10.3390/cancers17091593 - 7 May 2025
Viewed by 301
Abstract
Background: Neuroendocrine neoplasms (NENs) represent a heterogeneous group of malignancies that consist of two major subtypes: neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs). Glucagon-like peptide-1 receptor agonists (GLP-1Ra) have demonstrated favorable results in preclinical studies, but their impact on NEN outcomes remains unexplored. [...] Read more.
Background: Neuroendocrine neoplasms (NENs) represent a heterogeneous group of malignancies that consist of two major subtypes: neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs). Glucagon-like peptide-1 receptor agonists (GLP-1Ra) have demonstrated favorable results in preclinical studies, but their impact on NEN outcomes remains unexplored. Methods: Using the TriNetX US Research Network, we identified adult patients with NEN and either diabetes or obesity. After 1:1 propensity score matching based on demographics, comorbidities, procedures, and medication use, we compared survival outcomes between patients who received GLP-1Ra after NEN diagnosis and those who did not. Results: Among 32,464 eligible patients, 3139 received GLP-1Ra and 29,325 did not. After propensity matching, each cohort included 3043 patients with well-balanced baseline characteristics. During follow-up periods extending up to 15 years, all-cause mortality occurred in 356 (11.7%) GLP-1Ra users versus 753 (24.7%) non-users, representing a 13.0% absolute risk reduction (p < 0.001). GLP-1Ra use was associated with significantly improved survival (HR = 0.56, 95%CI = 0.49–0.63, p < 0.001). Both well-differentiated (HR = 0.52) and poorly differentiated tumors (HR = 0.56) showed significant improvement. Among primary sites, lung NENs demonstrated the most pronounced benefit (HR = 0.42). Tirzepatide showed the strongest association with reduced mortality (HR = 0.16), followed by semaglutide (HR = 0.27) and dulaglutide (HR = 0.52). Results: In this large propensity-matched study, GLP-1Ra use was associated with a 44.3% reduction in mortality risk among NEN patients with diabetes or obesity. The magnitude of the observed benefit suggests a potential role for GLP-1Ra as adjunctive therapy in this patient population. Prospective clinical trials are warranted to confirm these findings and explore underlying mechanisms. Full article
(This article belongs to the Section Clinical Research of Cancer)
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17 pages, 2200 KiB  
Article
The Clinical Outcomes and Safety of Sacituzumab Govitecan in Heavily Pretreated Metastatic Triple-Negative and HR+/HER2− Breast Cancer: A Multicenter Observational Study from Turkey
by Harun Muğlu, Kaan Helvacı, Bahadır Köylü, Mehmet Haluk Yücel, Özde Melisa Celayir, Umut Demirci, Başak Oyan Uluç, Gül Başaran, Taner Korkmaz, Fatih Selçukbiricik, Ömer Fatih Ölmez and Ahmet Bilici
Cancers 2025, 17(9), 1592; https://doi.org/10.3390/cancers17091592 - 7 May 2025
Viewed by 253
Abstract
Background/Objectives: Sacituzumab govitecan (SG) is an antibody–drug conjugate targeting Trop-2, approved for use in metastatic triple-negative breast cancer (mTNBC) and more recently in the hormone receptor-positive/HER2-negative (mHRPBC) subtype. While clinical trials have demonstrated its efficacy, real-world data—especially those involving both molecular subtypes—remain scarce. [...] Read more.
Background/Objectives: Sacituzumab govitecan (SG) is an antibody–drug conjugate targeting Trop-2, approved for use in metastatic triple-negative breast cancer (mTNBC) and more recently in the hormone receptor-positive/HER2-negative (mHRPBC) subtype. While clinical trials have demonstrated its efficacy, real-world data—especially those involving both molecular subtypes—remain scarce. This multicenter, retrospective study aimed to evaluate real-world observational data describing the clinical outcomes, safety, and prognostic factors associated with SG treatment in patients with mTNBC or mHRPBC. Methods: A total of 68 patients treated with SG between 2022 and 2025 were included from multiple oncology centers in Turkey. Patients with mTNBC were required to have received at least one prior chemotherapy line, while mHRPBC patients had received at least two prior chemotherapy lines in addition to cyclin-dependent kinase 4 and 6 inhibitors (CDK 4/6) plus hormone therapy. The clinical outcomes—including the progression-free survival (PFS), overall survival (OS), and objective response rate (ORR)—were evaluated. Univariate and multivariate analyses were performed to identify factors influencing outcomes. Adverse events (AEs) were also documented and graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5 (NCI-CTCAE v5.0). Results: The cohort included 35 (51.5%) mTNBC and 33 (48.5%) mHRPBC patients. The median PFS was 6.1 months, and the median OS was 12.5 months, with no significant differences between subtypes. The ORR was 52.9%, with a complete response observed in 10.3% of patients. A high Eastern Cooperative Oncology Group Performance Status (ECOG PS) and liver metastasis were independent predictors of poorer PFS and OS. Prior immunotherapy did not negatively impact SG’s efficacy. SG was generally well tolerated; the most common AEs were alopecia, anemia, neutropenia, and diarrhea. Treatment discontinuation due to AEs was rare (2.9%). Conclusions: SG was associated with similar clinical outcomes and tolerability in both the mTNBC and mHRPBC subtypes. Although the real-world PFS and OS outcomes mirror those seen in clinical trials, the absence of a control group means that these findings should be interpreted descriptively rather than as confirmation of treatment efficacy. Importantly, this study provides one of the first real-world datasets evaluating SG in the mHRPBC subgroup, highlighting its potential role beyond clinical trials. These results support SG as a valuable therapeutic option in heavily pretreated patients, warranting further prospective and biomarker-driven studies. Full article
(This article belongs to the Section Cancer Therapy)
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37 pages, 720 KiB  
Review
Exploring the Role of ADCs in Brain Metastases and Primary Brain Tumors: Insight and Future Directions
by Francesco Bruzzone, Chiara Barigazzi, Antonio Di Muzio, Isabel Tallarico, Angelo Dipasquale, Agnese Losurdo, Pasquale Persico, Pierina Navarria, Federico Pessina, Armando Santoro and Matteo Simonelli
Cancers 2025, 17(9), 1591; https://doi.org/10.3390/cancers17091591 - 7 May 2025
Viewed by 413
Abstract
Primary and secondary brain tumors have always been a challenge due to their high morbidity and poor prognosis. The incidence of brain metastasis is also increasing with the advent of effective new treatments. Traditional systemic treatments have historically had limited success, partly due [...] Read more.
Primary and secondary brain tumors have always been a challenge due to their high morbidity and poor prognosis. The incidence of brain metastasis is also increasing with the advent of effective new treatments. Traditional systemic treatments have historically had limited success, partly due to poor central nervous system (CNS) penetration. However, the advent in recent decades of new therapies that have shown high encephalic response rates are challenging this paradigm. ADCs represent a new class of compounds revolutionizing cancer treatment with high systemic response rates and lower toxicities. The continuing evolution of ADCs has shown that certain structural features such as payload, linker, and drug-to-antibody ratio (DAR) are essential in determining their efficacy at the encephalic level, and some ADCs have started to exhibit promising efficacy in treating primary and secondary brain tumors. Unfortunately, most patients with untreated encephalic metastases are excluded from clinical trials, with data primarily from retrospective studies or post hoc analyses. This review describes the early signs of ADC efficacy in brain tumors, the role of complementary treatments like radiation therapy, and critical points to improve ADC efficacy in brain malignancies. Full article
(This article belongs to the Section Cancer Metastasis)
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2 pages, 349 KiB  
Correction
Correction: Będkowska et al. What We Know and Do Not Yet Know About the Canine Model of Lymphoma in Human Medicine—The Current State of Knowledge. Cancers 2025, 17, 596
by Daria Będkowska, Sara Al-Ameri, Agnieszka Wieczorek, Joanna Bubak and Marta Miszczak
Cancers 2025, 17(9), 1590; https://doi.org/10.3390/cancers17091590 - 7 May 2025
Viewed by 99
Abstract
In the original publication [...] Full article
(This article belongs to the Section Clinical Research of Cancer)
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20 pages, 855 KiB  
Review
Geriatric Assessment and Management, Prehabilitation and Rehabilitation for Older Aldults with Non-Colorectal Digestive Cancers
by Amélie Aregui, Janina Estrada, Madeleine Lefèvre, Anna Carteaux-Taieb, Geoffroy Beraud-Chaulet, Pascal Hammel, Virginie Fossey-Diaz and Thomas Aparicio
Cancers 2025, 17(9), 1589; https://doi.org/10.3390/cancers17091589 - 7 May 2025
Viewed by 221
Abstract
Background: The incidence of cancer in older patients is high, reaching 2.3 million world-wide in 2018 for patients aged over 80. Because the characteristics of this population make therapeutic choices difficult, co-management between geriatricians and other cancer specialists has gradually become essential. Methods: [...] Read more.
Background: The incidence of cancer in older patients is high, reaching 2.3 million world-wide in 2018 for patients aged over 80. Because the characteristics of this population make therapeutic choices difficult, co-management between geriatricians and other cancer specialists has gradually become essential. Methods: This narrative review aims to synthesize current data on the contribution of geriatric assessment in the management of elderly patients with non-colorectal digestive cancers. Oncogeriatric assessment is multi-domain, including the evaluation of co-morbidities, autonomy, nutrition, cognition, mood, and functional assessment. Results: Oncogeriatric parameters are predictive of mortality and adverse events. In the peri-operative phase of non-colorectal digestive cancer surgical management, geriatric management can assist in the decision-making process, identify frailties, and arrange a specific and personalized trimodal preoperative rehabilitation program, including nutritional management, adapted physical activity, and psychological care. Its aim is to limit the risks of confusion and of decompensation of comorbidities, mainly cardio-respiratory, which is associated with the highest morbidity in biliary-pancreatic surgery for older adults, facilitate recovery of previous autonomy when possible, and shorten hospital stay. For metastatic cancers, or during multimodal management, such as peri-operative chemotherapy for localized gastric cancers or pre-operative radio-chemotherapy for oesophageal or rectal cancers, specific assessment of the tolerance of chemotherapy is necessary. Neuropathic toxicity and chemobrain have a greater impact on elderly patients, with an increased loss of autonomy. Joint geriatric management can reduce the rate of grade 3–5 adverse effects of chemotherapy in particular and improve quality of life. Conclusions: Co-management between geriatricians and other specialties should be encouraged wherever possible. Full article
(This article belongs to the Special Issue Treatment Outcomes in Older Adults with Cancer)
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28 pages, 1933 KiB  
Review
Refining Lung Cancer Brain Metastasis Models for Spatiotemporal Dynamic Research and Personalized Therapy
by Ying Chen, Ao Zhang, Jingrong Wang, Hudan Pan, Liang Liu and Runze Li
Cancers 2025, 17(9), 1588; https://doi.org/10.3390/cancers17091588 - 7 May 2025
Viewed by 278
Abstract
Lung cancer brain metastasis (LCBM) is a major contributor to cancer-related mortality, with a median survival of 8–16 months following diagnosis, despite advances in therapeutic strategies. The development of clinically relevant animal models is crucial for understanding the metastatic cascade and assessing therapies [...] Read more.
Lung cancer brain metastasis (LCBM) is a major contributor to cancer-related mortality, with a median survival of 8–16 months following diagnosis, despite advances in therapeutic strategies. The development of clinically relevant animal models is crucial for understanding the metastatic cascade and assessing therapies that can penetrate the blood–brain barrier (BBB). This review critically evaluates five primary LCBM modeling approaches—orthotopic implantation, intracardiac injection, stereotactic intracranial injection, carotid artery injection, and tail vein injection—focusing on their clinical applicability. We systematically compare their ability to replicate human metastatic pathophysiology and highlight emerging technologies for personalized therapy screening. Additionally, we analyze breakthrough strategies in central nervous system (CNS)-targeted drug delivery, including microparticle targeted delivery systems designed to enhance brain accumulation. By incorporating advances in single-cell omics and AI-driven metastasis prediction, this work provides a roadmap for the next generation of LCBM models, aimed at bridging preclinical and clinical research. Full article
(This article belongs to the Section Cancer Metastasis)
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16 pages, 794 KiB  
Article
Unmet Needs and Their Impact on Quality of Life and Symptoms in Myelodysplastic Neoplasm Patients and Caregivers
by Elena Crisà, Daniela Cilloni, Marta Riva, Enrico Balleari, Daniela Barraco, Beatrice Manghisi, Lorenza Borin, Michela Calmasini, Anna Calvisi, Isabella Capodanno, Matteo Giovanni Della Porta, Elisa Diral, Bruno Fattizzo, Susanna Fenu, Stefania Paolini, Carlo Finelli, Claudio Fozza, Chiara Frairia, Valentina Giai, Mauro Turrini, Maria Antonia Isoni, Federico Itri, Luca Maurillo, Alfredo Molteni, Giuseppe Alberto Palumbo, Anna Maria Pelizzari, Federica Pilo, Antonella Poloni, Costanza Bosi, Grazia Sanpaolo, Rosaria Sancetta, Cristina Amato, Valeria Santini, Maria Teresa Voso, Sam Salek, Tatyana Ionova, Annamaria Nosari and Esther Natalie Olivaadd Show full author list remove Hide full author list
Cancers 2025, 17(9), 1587; https://doi.org/10.3390/cancers17091587 - 7 May 2025
Viewed by 216
Abstract
Background/Objectives: The aim of this study was to assess the unmet needs of myelodysplastic neoplasm (MDS) patients and their caregivers, focusing on how these needs impact quality of life (QoL) and daily functioning. MDS predominantly affects older adults. It is often complicated by [...] Read more.
Background/Objectives: The aim of this study was to assess the unmet needs of myelodysplastic neoplasm (MDS) patients and their caregivers, focusing on how these needs impact quality of life (QoL) and daily functioning. MDS predominantly affects older adults. It is often complicated by severe red blood cell transfusion-dependent anemia and may require frequent hospital visits, conferring a substantial burden on patients and caregivers. Methods: A national survey was conducted between June 2022 and May 2023 in 46 hematology centers across Italy, involving 259 patients and 105 caregivers. The survey included validated QoL tools (QOL-E and HM-PRO) to measure the impact of disease and treatments on health-related QoL and symptoms. Results: Of the 259 patients surveyed, 42% were transfusion-dependent, with 45% reporting distress related to hospital travel, which was significantly associated with lower QoL scores (QOL-E physical score 50.0 vs. 62.5, p < 0.001). Transfusion dependency led to worse outcomes across physical, emotional, and social domains (HM-PRO Part A score 59.8 vs. 23.7, p < 0.001). Anxiety affected 66% of patients, while 56% reported feeling emotionally distressed. Forty-eight percent of patients required a caregiver, and among caregivers, 29% reported significant disruption to their work, including changing their job or reduced hours. Patients requiring frequent hospital visits showed notably worse QoL scores (HM-PRO emotional score 56.8 vs. 31.8, p < 0.001). Conclusions: This study identified substantial unmet needs for MDS patients, particularly in addressing the heavy burden of transfusions and hospital visits. Both patients and caregivers experienced significant impact on daily life and on QoL, highlighting the urgent need for treatments that reduce hospital dependency, improve patient outcomes, and alleviate the caregiver burden. Full article
(This article belongs to the Special Issue Symptom Burden in Cancer: Assessment and Management)
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24 pages, 1770 KiB  
Review
Unraveling Venetoclax Resistance: Navigating the Future of HMA/Venetoclax-Refractory AML in the Molecular Era
by Theodora Chatzilygeroudi, Theodoros Karantanos and Vasiliki Pappa
Cancers 2025, 17(9), 1586; https://doi.org/10.3390/cancers17091586 - 7 May 2025
Viewed by 419
Abstract
Acute myeloid leukemia (AML) has traditionally been linked to a poor prognosis, particularly in older patients who are ineligible for intensive chemotherapy. The advent of Venetoclax, a powerful oral BH3 mimetic targeting anti-apoptotic protein BCL2, has significantly advanced AML treatment. Its combination with [...] Read more.
Acute myeloid leukemia (AML) has traditionally been linked to a poor prognosis, particularly in older patients who are ineligible for intensive chemotherapy. The advent of Venetoclax, a powerful oral BH3 mimetic targeting anti-apoptotic protein BCL2, has significantly advanced AML treatment. Its combination with the hypomethylating agent azacitidine (AZA/VEN) has become a standard treatment for this group of AML patients, demonstrating a 65% overall response rate and a median overall survival of 14.7 months, compared to 22% and 8 months with azacitidine monotherapy, respectively. However, resistance and relapses remain common, representing a significant clinical challenge. Recent studies have identified molecular alterations, such as mutations in FLT3-ITD, NRAS/KRAS, TP53, and BAX, as major drivers of resistance. Additionally, other factors, including metabolic changes, anti-apoptotic protein expression, and monocytic or erythroid/megakaryocytic differentiation status, contribute to treatment failure. Clinical trials are exploring strategies to overcome venetoclax resistance, including doublet or triplet therapies targeting IDH and FLT3 mutations; novel epigenetic approaches; menin, XPO1, and MDM2 inhibitors; along with immunotherapies like monoclonal antibodies and antibody–drug conjugates. A deeper understanding of the molecular mechanisms of resistance through single-cell analysis will be crucial for developing future therapeutic strategies. Full article
(This article belongs to the Special Issue Acute Myeloid Leukemia in Adults)
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13 pages, 771 KiB  
Article
Work Ability in Patients with Chronic Myeloid Leukemia: A Danish Nationwide Cohort Study
by Eva Futtrup Maksten, Jonas Faartoft Jensen, Gitte Thomsen, Ditte Rechter Zenas, Maren Poulsgaard Jørgensen, Lene Udby, Kirsten Fonager and Marianne Tang Severinsen
Cancers 2025, 17(9), 1585; https://doi.org/10.3390/cancers17091585 - 7 May 2025
Viewed by 145
Abstract
Background/Objectives: Patients with chronic myeloid leukemia (CML) have a long life expectancy due to modern treatment. However, treatment may have adverse effects that hamper work ability. Methods: Patients aged 25–60 years diagnosed in 2002–2020 were included in this nationwide matched cohort [...] Read more.
Background/Objectives: Patients with chronic myeloid leukemia (CML) have a long life expectancy due to modern treatment. However, treatment may have adverse effects that hamper work ability. Methods: Patients aged 25–60 years diagnosed in 2002–2020 were included in this nationwide matched cohort study examining work ability from diagnosis (index date), including the need for permanent disability compensation (flexible job or disability pension). Each patient was matched 1:5 on sex, birth year, and level of comorbidity with citizens from the general Danish population without CML. The risks of requiring flexible job and disability pension were calculated by cause-specific hazard ratios (HRs) using Cox proportional hazards regression, and the Aalen–Johansen estimator was used to determine cumulative risks. Results: A total of 489 patients with CML and 2445 matched comparators were included. The median age was 46 years, and males comprised 59.5% of the cohort. Matched comparators were more likely to work at index date and 1, 3, 5, and 10 years after the index date (p < 0.001). The HRs of requiring both flexible job (HR 8.7 (95% confidence interval (CI): 6.1;12.2, p < 0.001)) and disability pension (HR 3.7 (95% CI: 2.8;4.9, p < 0.001)) were higher among patients diagnosed with CML compared to matched comparators. The cumulative risk of requiring flexible job and disability pension also increased in patients with CML compared to matched comparators (p < 0.001). Conclusions: Patients with CML have a reduced work ability compared to the general population. More research is needed to determine the cause of their loss of ability to work. Full article
(This article belongs to the Special Issue Quality of Life and Side Effects Management in Cancer Treatment (Volume II))
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16 pages, 7408 KiB  
Article
Treatment of Pancreatic Cancer Using Near-Infrared Photoimmunotherapy Targeting Cancer-Associated Fibroblasts in Combination with Anticancer Chemotherapeutic Drug
by Hiroki Yonemura, Masaki Kuwatani, Kohei Nakajima, Atsushi Masamune, Mikako Ogawa and Naoya Sakamoto
Cancers 2025, 17(9), 1584; https://doi.org/10.3390/cancers17091584 - 7 May 2025
Viewed by 230
Abstract
Background: Pancreatic ductal adenocarcinoma (PDAC), which has a poor prognosis, involves an overabundance of fibroblasts and extracellular matrix. Cancer-associated fibroblasts (CAFs) are critical for providing structural support by secreting soluble factors and extracellular matrix proteins into the stroma. We assessed the potential [...] Read more.
Background: Pancreatic ductal adenocarcinoma (PDAC), which has a poor prognosis, involves an overabundance of fibroblasts and extracellular matrix. Cancer-associated fibroblasts (CAFs) are critical for providing structural support by secreting soluble factors and extracellular matrix proteins into the stroma. We assessed the potential of near-infrared photoimmunotherapy (NIR-PIT) targeting CAFs in PDAC. Methods: PDAC cells (Capan-1 and SUIT-2) and CAFs (hPSC-5) were used. Anti-human fibroblast activation protein (FAP)/podoplanin (PDPN) antibodies were used to bind to CAFs and conjugates with the specific photosensitizer IRDye®700DX (IR700) to investigate the effects of NIR-PIT. Thereafter, BALB/c Slc-nu/nu mice were transplanted with Capan-1 and/or CAFs and treated with gemcitabine (GEM) with or without NIR-PIT. Results: The binding rate of anti-FAP antibody-AlexaFluor®488 conjugate to hPSC-5 cells was high, whereas that of the anti-PDPN antibody-conjugate was not. The incubation of anti-FAP antibody-IR700 conjugate (αFAP-IR700) with hPSC-5 cells for 3 h led to maximal fluorescence on the surface of hPSC-5 cells. When NIR-PIT with αFAP-IR700 was performed in the co-culture group of Capan-1 and hPSC-5 cells, the proliferative capacity of Capan-1 cells decreased to the same level as that when Capan-1 cells were cultured alone (p < 0.05). In vivo, compared with the GEM group, the NIR-PIT with the GEM group showed a significant reduction in the tumor volume (day 28: 79 vs. 382 mm3, p < 0.05). Tumor volumes in the NIR-PIT group were not reduced compared with those in the control group. Conclusions: Combining NIR-PIT with conventional chemotherapy to target CAFs may enhance the anticancer effects on PDAC. Full article
(This article belongs to the Special Issue Multimodal Treatment for Pancreatic Cancer)
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2 pages, 654 KiB  
Correction
Correction: Turchi et al. CELF2 Sustains a Proliferating/OLIG2+ Glioblastoma Cell Phenotype via the Epigenetic Repression of SOX3. Cancers 2023, 15, 5038
by Laurent Turchi, Nathalie Sakakini, Gaelle Saviane, Béatrice Polo, Mirca Saras Saurty-Seerunghen, Mathieu Gabut, Corine Auge Gouillou, Vincent Guerlais, Claude Pasquier, Marie Luce Vignais, Fabien Almairac, Hervé Chneiweiss, Marie-Pierre Junier, Fanny Burel-Vandenbos and Thierry Virolle
Cancers 2025, 17(9), 1583; https://doi.org/10.3390/cancers17091583 - 7 May 2025
Viewed by 107
Abstract
In the original publication [...] Full article
(This article belongs to the Special Issue Brain Cancer Stem Cells in Children and Adults)
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18 pages, 1647 KiB  
Review
The Evolving Landscape of Radiomics in Gliomas: Insights into Diagnosis, Prognosis, and Research Trends
by Mehek Dedhia and Isabelle M. Germano
Cancers 2025, 17(9), 1582; https://doi.org/10.3390/cancers17091582 - 6 May 2025
Viewed by 269
Abstract
Gliomas are the most prevalent and aggressive form of primary brain tumors. The clinical challenge in managing patients with this disease revolves around the difficulty of diagnosis, both at onset and during treatment, and the scarcity of prognostic outcome indicators. Radiomics involves the [...] Read more.
Gliomas are the most prevalent and aggressive form of primary brain tumors. The clinical challenge in managing patients with this disease revolves around the difficulty of diagnosis, both at onset and during treatment, and the scarcity of prognostic outcome indicators. Radiomics involves the extraction of quantitative features from medical images with the help of artificial intelligence, positioning it as a promising tool to be integrated into the care of glioma patients. Using data from 52 studies and 12,482 patients over two years, this review explores how radiomics can enhance the initial diagnosis of gliomas, especially helping to differentiate treatment stages that may be difficult for the human eye to do otherwise. Radiomics has also been able to identify patient-specific tumor molecular signatures for targeted treatments without the need for invasive surgical biopsy. Such an approach could lead to earlier interventions and more precise individualized therapies that are tailored to each patient. Additionally, it could be integrated into clinical practice to improve longitudinal diagnosis during treatment and predict tumor recurrence. Finally, radiomics has the potential to predict clinical outcomes, helping both patients and providers set realistic expectations. While this field is continuously evolving, future research should conduct such studies in larger, multi-institutional cohorts to enhance generalizability and applicability in clinical practice and focus on combining radiomics with other modalities to improve its predictive accuracy and clinical utility. Full article
(This article belongs to the Special Issue Radiomics in Cancer)
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21 pages, 485 KiB  
Review
BAP1 Mutations and Pleural Mesothelioma: Genetic Insights, Clinical Implications, and Therapeutic Perspectives
by Susana Cedres, Augusto Valdivia, Ilaria Priano, Pedro Rocha, Patricia Iranzo, Nuria Pardo, Alex Martinez-Marti and Enriqueta Felip
Cancers 2025, 17(9), 1581; https://doi.org/10.3390/cancers17091581 - 6 May 2025
Viewed by 210
Abstract
Pleural mesothelioma (PM) is a locally aggressive tumor associated with asbestos exposure. Despite legislative efforts to regulate asbestos use, its incidence continues to rise in some parts of the world. Chemotherapy and immunotherapy have improved survival in PM patients, but overall survival remains [...] Read more.
Pleural mesothelioma (PM) is a locally aggressive tumor associated with asbestos exposure. Despite legislative efforts to regulate asbestos use, its incidence continues to rise in some parts of the world. Chemotherapy and immunotherapy have improved survival in PM patients, but overall survival remains poor. Molecular analysis of PM patients has shown that most alterations occur in tumor suppressor genes, with BAP1 being the most frequently affected. Patients with germline BAP1 mutations have been reported to have a better prognosis, but this is not observed in those with somatic mutations. Interest in developing drugs targeting patients with BAP1 loss has led to several phase II studies in recent years. Unfortunately, initial results have not been very promising. In this review, we conclude that, at this time, with the contradictory results from studies and the limited number of patients evaluated, BAP1, the most commonly altered gene in PM, is not yet suitable for use in clinical practice as a prognostic or predictive factor. Future studies are needed to establish the prognostic or predictive value of BAP1. Full article
(This article belongs to the Special Issue Biomarkers and Targeted Therapy in Malignant Pleural Mesothelioma)
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31 pages, 1101 KiB  
Review
Particle Therapy to Overcome Cancer Radiation Resistance: “ARCHADE” Consortium Updates in Radiation Biology
by Samuel Valable, Mathieu Césaire, Kilian Lecrosnier, Antoine Gilbert, Mihaela Tudor, Guillaume Vares, Dounia Houria Hamdi, Ousseynou Ben Diouf, Thao Nguyen Pham, Julie Coupey, Juliette Thariat, Paul Lesueur, Elodie Anne Pérès, Juliette Aury-Landas, Zacharenia Nikitaki, Siamak Haghdoost, Carine Laurent, Jean-Christophe Poully, Jacques Balosso, Myriam Bernaudin, Diana I. Savu and François Chevalieradd Show full author list remove Hide full author list
Cancers 2025, 17(9), 1580; https://doi.org/10.3390/cancers17091580 - 6 May 2025
Viewed by 249
Abstract
Radiation therapy is a medical treatment that uses high doses of radiation to kill or damage cancer cells. It works by damaging the DNA within the cancer cells, ultimately causing cell death. Radiotherapy can be used as a primary treatment, adjuvant treatment in [...] Read more.
Radiation therapy is a medical treatment that uses high doses of radiation to kill or damage cancer cells. It works by damaging the DNA within the cancer cells, ultimately causing cell death. Radiotherapy can be used as a primary treatment, adjuvant treatment in combination with surgery or chemotherapy or palliative treatment to relieve symptoms in advanced cancer stages. Radiation therapy is constantly improving in order to enhance the effect on cancer cells and reduce the side effects on healthy tissues. Our results clearly demonstrate that proton therapy and, even more, carbon ion therapy appear as promising alternatives to overcome the radioresistance of various tumors thanks to less dependency on oxygen and a better ability to kill cancer stem cells. Interestingly, hadrons also retain the advantages of radiosensitization approaches. These data confirm the great ability of hadrons to spare healthy tissue near the tumor via various mechanisms (reduced lymphopenia, bystander effect, etc.). Technology and machine improvements such as image-guided radiotherapy or particle therapies can improve treatment quality and efficacy (dose deposition and biological effect) in tumors while increasingly sparing healthy tissues. Radiation biology can help to understand how cancer cells resist radiation (hypoxia, DNA repair mechanisms, stem cell status, cell cycle position, etc.), how normal tissues may display sensitivity to radiation and how radiation effects can be increased with either radiosensitizers or accelerated particles. All these research topics are under investigation within the ARCHADE research community in France. By focusing on these areas, radiotherapy can become more effective, targeted and safe, enhancing the overall treatment experience and outcomes for cancer patients. Our goal is to provide biological evidence of the therapeutic advantages of hadrontherapy, according to the tumor characteristics. This article aims to give an updated view of our research in radiation biology within the frame of the French “ARCHADE association” and new perspectives on research and treatment with the C400 multi-ions accelerator prototype. Full article
(This article belongs to the Special Issue New Therapeutic Strategies of Radioresistant Tumours by Radiosensitization)
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14 pages, 749 KiB  
Article
Clinical, Sociodemographic, and Facility-Related Factors Influencing HER2-Targeted Therapy in Metastatic Hormone Receptor-Negative, HER2-Positive Breast Cancer
by Ismail Ajjawi, Alejandro Rios, Wei Wei, Tristen S. Park and Maryam B. Lustberg
Cancers 2025, 17(9), 1579; https://doi.org/10.3390/cancers17091579 - 6 May 2025
Viewed by 265
Abstract
Background/Objectives: The use of HER2-targeted therapies has significantly improved survival outcomes in metastatic hormone receptor-negative, HER2-positive (HR−/HER2+) breast cancer. However, factors influencing their adoption remain unclear. This study examines clinical, sociodemographic, and facility-related determinants of HER2-targeted therapy utilization in metastatic HR−/HER2+ breast [...] Read more.
Background/Objectives: The use of HER2-targeted therapies has significantly improved survival outcomes in metastatic hormone receptor-negative, HER2-positive (HR−/HER2+) breast cancer. However, factors influencing their adoption remain unclear. This study examines clinical, sociodemographic, and facility-related determinants of HER2-targeted therapy utilization in metastatic HR−/HER2+ breast cancer. Methods: We conducted a retrospective cohort study of metastatic HR−/HER2+ breast cancer patients from the NCDB (2013–2020), categorizing them into HER2-targeted therapy recipients and non-recipients. Patients with missing key variables were excluded. Time periods were divided as pre-2015, 2016–2018, and 2019–2020 to reflect evolving treatment availability and uptake in the United States. Univariable and multivariable logistic regression identified factors associated with HER2-targeted therapy use. Cox proportional hazards regression and log-rank tests assessed overall survival. Results: Among 3060 metastatic HR−/HER2+ breast cancer patients, 2318 (75.8%) received HER2-targeted therapy. HER2-targeted therapy utilization increased from 64.6% in 2013 to 80.9% in 2016, marking an early period of rapid uptake. Usage remained consistently high from 2016 to 2018, followed by a slight decline and stabilization around 75% from 2019 to 2020. Factors positively associated with therapy use included diagnosis in 2016–2018 (OR 1.93, p < 0.001) and 2019–2020 (1.88, p < 0.001), private insurance (OR 1.76, p < 0.001), and treatment at academic facilities (OR 1.39, p = 0.031). Reduced likelihood of therapy use was observed in patients aged 71+ (OR 0.52, p < 0.001), Black race (OR 0.78, p = 0.018), Medicare insurance (OR 0.64, p < 0.001), and treatment at rural facilities (OR 0.59, p = 0.022). HER2-targeted therapy was associated with significantly improved survival (median 5.08 vs. 1.27 years, log-rank p < 0.001) and lower mortality risk (HR 0.52, p < 0.001). Conclusions: The adoption of HER2-targeted therapy has increased in recent years, yet disparities persist in access and utilization. Our findings highlight the need to address sociodemographic and facility-related barriers to ensure equitable treatment and improved survival outcomes for all patients. Full article
(This article belongs to the Special Issue Disparities in Cancer Prevention, Screening, Diagnosis and Management)
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23 pages, 2873 KiB  
Review
Sestrins in Carcinogenesis—The Firefighters That Sometimes Stoke the Fire
by Alexander Haidurov and Andrei V. Budanov
Cancers 2025, 17(9), 1578; https://doi.org/10.3390/cancers17091578 - 6 May 2025
Viewed by 295
Abstract
Sestrins (SESN1-3) are a family of stress-responsive proteins that regulate cellular metabolism and redox balance, both of which are frequently disrupted in cancer. As direct targets of stress-responsive transcription factors, including tumour suppressor p53, Sestrins function as leucine-dependent inhibitors of mTORC1 and potent [...] Read more.
Sestrins (SESN1-3) are a family of stress-responsive proteins that regulate cellular metabolism and redox balance, both of which are frequently disrupted in cancer. As direct targets of stress-responsive transcription factors, including tumour suppressor p53, Sestrins function as leucine-dependent inhibitors of mTORC1 and potent antioxidants. Their downregulation is widely observed across multiple cancers and is associated with increased tumour growth and poor prognosis. Despite their consistent tumour-suppressive effects through mTORC1 inhibition and promotion of p53-dependent apoptosis, Sestrins exhibit a limited role in tumour initiation, which appears to be context-dependent. Their antioxidant activity reduces oxidative damage, thereby protecting against genomic instability and other cancer-promoting events. However, in certain contexts, Sestrins may promote tumour survival and progression by stimulating pro-survival pathways, such as AKT signalling through mTORC2 activation. This review examines the molecular mechanisms underlying these dual functions, with a particular focus on mTOR signalling and oxidative stress. We also discuss Sestrin expression patterns and functional outcomes in various cancer types, including lung, liver, colon, skin, prostate, and follicular lymphomas, highlighting their potential as diagnostic markers and therapeutic targets. Full article
(This article belongs to the Section Cancer Pathophysiology)
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10 pages, 537 KiB  
Article
Patterns of Comorbidities in Lung Cancer Patients and Survival
by Alessandra Buja, Marcello Di Pumpo, Massimo Rugge, Manuel Zorzi, Federico Rea, Ilaria Pantaleo, Giovanna Scroccaro, Pierfranco Conte, Leonardo Rigon, Giorgio Arcara, Giulia Pasello and Valentina Guarneri
Cancers 2025, 17(9), 1577; https://doi.org/10.3390/cancers17091577 - 6 May 2025
Viewed by 207
Abstract
Introduction: Comorbidities affect diagnosis and treatments in cancer patients. This study explores the prevalence and patterns of comorbidities in non-small cell lung cancer (NSCLC) patients and their association with survival. Materials and Methods: This retrospective population-based cohort study included 1674 incident NSCLC patients. [...] Read more.
Introduction: Comorbidities affect diagnosis and treatments in cancer patients. This study explores the prevalence and patterns of comorbidities in non-small cell lung cancer (NSCLC) patients and their association with survival. Materials and Methods: This retrospective population-based cohort study included 1674 incident NSCLC patients. Comorbidities were classified based on the ICD-9-CM system, with 13 disease categories analyzed. Patients with more than two comorbidities were classified into three mutually exclusive and exhaustive latent classes (Latent Class Analysis [LCA]). The optimal number of latent classes was determined by applying the Akaike Information Criterion. Cox regression models were run to assess overall and cancer-specific mortality, adjusting for the comorbidity groups, sex, age, and stage at diagnosis. Results: In 1674 NSCLC patients, the most prevalent medical conditions were respiratory (35.8%) and cardiovascular (33.5%). The Cox regression showed that even one comorbidity is associated with an increased hazard of overall mortality (HR = 1.33, 95%CI: 1.11–1.59, p = 0.002). LCA-derived Class-1 (cardiovascular-respiratory and endocrine) reported HR = 1.74 (95%CI: 1.39–2.17, p < 0.001), Class-2 (multi-organ) HR = 1.44 (95%CI: 1.18–1.77, p < 0.001), and Class-3 (socio-multifactorial-neuro) HR = 1.62 (95%CI: 1.36–1.93, p < 0.001). Instead, in patients with one comorbidity, NSCLC-specific mortality showed no significant trend towards increased risk (HR = 1.17, 95%CI: 1.00–1.43, p = 0.114). Significant associations emerged between NSCLC-specific mortality and LCA-classes: Class-1: HR = 1.49 (95%CI: 1.20–1.91, p = 0.001); Class-2 HR = 1.25 (95%CI: 1.0–1.57 p = 0.048); and Class-3: HR = 1.23 (95%CI: 1.00–1.48, p = 0.035). Conclusions: The adverse impact of comorbidities on NSCLC-specific mortality requires their inclusion as risk factors in cancer treatment and prognosis. Full article
(This article belongs to the Section Cancer Epidemiology and Prevention)
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14 pages, 887 KiB  
Review
May Patients Receiving GLP-1 Agonists Be at Lower Risk of Prostate Cancer Aggressiveness and Progression?
by Julia Drewa, Katarzyna Lazar-Juszczak, Jan Adamowicz and Kajetan Juszczak
Cancers 2025, 17(9), 1576; https://doi.org/10.3390/cancers17091576 - 6 May 2025
Viewed by 224
Abstract
Introduction: GLP-1 receptor agonists are valuable therapeutic agents for managing obesity and type 2 diabetes. The link between prostate cancer and obesity was described. The modulation of incretin hormone-dependent pathways may decrease the prostate cancer aggressiveness and progression. Objectives: The purpose of this [...] Read more.
Introduction: GLP-1 receptor agonists are valuable therapeutic agents for managing obesity and type 2 diabetes. The link between prostate cancer and obesity was described. The modulation of incretin hormone-dependent pathways may decrease the prostate cancer aggressiveness and progression. Objectives: The purpose of this study was to review and summarize the literature on the role of GLP-1 agonists in prostate cancer. Material & Methods: We performed a scoping literature review of PubMed from January 2002 to February 2025. Search terms included “glucagon-peptide like 1”, “incretin hormone”, “GLP-1 receptor agonist”, and “prostate cancer”. Secondary search involved reference lists of eligible articles. The key criterion was to identify studies that included GLP-1 receptor, incretin hormones, GLP-1 receptor agonists, and their role in prostate cancer development. Results: 77 publications were selected for inclusion in this review. The studies contained in publications allowed us to summarize the data on the role of GLP-1 receptor and it’s agonists in prostate cancer biology and development. The following review aims to discuss and provide information about the role of incretin hormones in prostate cancer pathogenesis and its clinical implication in patients with prostate cancer. Conclusion: Incretin hormone-dependent pathways play an important role in prostate cancer pathogenesis. Moreover, GLP-1 receptor agonists seems to be a promising therapeutical agents when it comes to finding new therapies in patients with more aggressive and/or advanced stages of prostate cancer. Full article
(This article belongs to the Special Issue New Insights into General, Functional and Oncologic Urology)
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38 pages, 11406 KiB  
Article
Detection of Local Prostate Cancer Recurrence from PET/CT Scans Using Deep Learning
by Marko Korb, Hülya Efetürk, Tim Jedamzik, Philipp E. Hartrampf, Aleksander Kosmala, Sebastian E. Serfling, Robin Dirk, Kerstin Michalski, Andreas K. Buck, Rudolf A. Werner, Wiebke Schlötelburg and Markus J. Ankenbrand
Cancers 2025, 17(9), 1575; https://doi.org/10.3390/cancers17091575 - 6 May 2025
Viewed by 258
Abstract
Background: Prostate cancer (PC) is a leading cause of cancer-related deaths in men worldwide. PSMA-directed positron emission tomography (PET) has shown promising results in detecting recurrent PC and metastasis, improving the accuracy of diagnosis and treatment planning. To evaluate an artificial intelligence (AI) [...] Read more.
Background: Prostate cancer (PC) is a leading cause of cancer-related deaths in men worldwide. PSMA-directed positron emission tomography (PET) has shown promising results in detecting recurrent PC and metastasis, improving the accuracy of diagnosis and treatment planning. To evaluate an artificial intelligence (AI) model based on [18F]-prostate specific membrane antigen (PSMA)-1007 PET datasets for the detection of local recurrence in patients with prostate cancer. Methods: We retrospectively analyzed 1404 [18F]-PSMA-1007 PET/CTs from patients with histologically confirmed prostate cancer. Artificial neural networks were trained to recognize the presence of local recurrence based on the PET data. First, the hyperparameters were optimized for an initial model (model A). Subsequently, the bladder was localized using an already published model and a model (model B) was trained only on a 20 cm cube around the bladder. Finally, two separate models were trained on the same section depending on the prostatectomy status (model C (post-prostatectomy) and model D (non-operated)). Results: Model A achieved an accuracy of 56% on the validation data. By restricting the region to the area around the bladder, Model B achieved a validation accuracy of 71%. When validating the specialized models according to prostatectomy status, model C achieved an accuracy of 77% and model D an accuracy of 77%. All models achieved accuracies of almost 100% on the training data, indicating overfitting. Conclusions: For the presented task, 1404 examinations were insufficient to reach an accuracy of over 90% even when employing data augmentation, including additional metadata and performing automated hyperparameter optimization. The low F1-score and AUC values indicate that none of the presented models produce reliable results. However, we will facilitate future research and the development of better models by openly sharing our source code and all pre-trained models for transfer learning. Full article
(This article belongs to the Special Issue Bridging the Gap: Integrating AI into Clinical Practice for Oncological PET/CT Imaging)
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23 pages, 1239 KiB  
Article
Emotional Functioning in Long-Term Breast Cancer Survivors: A Cross-Sectional Study on Its Influence and Key Predictors
by Francisco Álvarez-Salvago, Sandra Atienzar-Aroca, Clara Pujol-Fuentes, Maria Figueroa-Mayordomo, Cristina Molina-García, Palmira Gutiérrez-García and Jose Medina-Luque
Cancers 2025, 17(9), 1574; https://doi.org/10.3390/cancers17091574 - 6 May 2025
Viewed by 273
Abstract
Background/Objectives: This study aimed to analyze the relationship between emotional functioning and health status in long-term breast cancer survivors (LTBCSs). Additionally, it sought to identify factors that could influence emotional functioning in this population at least five years after cancer diagnosis. Methods [...] Read more.
Background/Objectives: This study aimed to analyze the relationship between emotional functioning and health status in long-term breast cancer survivors (LTBCSs). Additionally, it sought to identify factors that could influence emotional functioning in this population at least five years after cancer diagnosis. Methods: This cross-sectional observational study included 80 LTBCSs, classified into the following two groups, according to their emotional functioning: those experiencing psychological distress (≤90) and those with satisfactory psychological well-being (≥91). The study examined various factors at least five years post-diagnosis, including sociodemographic and clinical characteristics, health-related quality of life (HRQoL), mood state, self-perceived physical fitness, physical activity (PA) level, pain, and cancer-related fatigue (CRF). ANOVA, Mann–Whitney U, and Chi-square tests were conducted, along with correlation and multiple regression analysis. Effect sizes were calculated using Cohen’s d. Results: Among the 80 LTBCSs, 47.50% reported psychological distress, while 52.50% maintained satisfactory psychological well-being. Participants in the psychological distress group exhibited significantly poorer HRQoL, lower mood, and reduced self-perceived physical fitness, as well as higher levels of physical inactivity, pain, and CRF (p < 0.05). Regression analysis revealed that “role functioning” (β = 0.59; p < 0.01), “cognitive functioning” (β = 0.26; p < 0.01), “self-perceived physical fitness” (β = 0.20; p = 0.02), and “sadness–depression” (β = 0.18; p = 0.04) were significant predictors of emotional functioning (r2 adjusted = 0.642). Conclusions: These results emphasize the association between emotional functioning and health status in LTBCSs. Role functioning, cognitive functioning, self-perceived physical fitness, and mood state were identified as relevant factors influencing emotional well-being in this population. Considering these relationships, integrating psychological and physical assessments into survivorship care could support the early detection of at-risk individuals. This approach could also guide interventions to improve their long-term well-being and HRQoL. Full article
(This article belongs to the Special Issue Latest Advancements in Health-Related Quality of Life Research in Cancer Survivorship (2nd Edition))
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8 pages, 1365 KiB  
Article
LFHP-1c Attenuates Hepatocellular Carcinoma Viability In Vitro Independent of PGAM5
by Ganesan Muthusamy, Chin-Chi Liu and Andrea N. Johnston
Cancers 2025, 17(9), 1573; https://doi.org/10.3390/cancers17091573 - 6 May 2025
Viewed by 235
Abstract
Background/Objectives: Upregulation of phosphoglycerate mutase 5 (PGAM5) is correlated with reduced survival outcomes in hepatocellular carcinoma (HCC). PGAM5 knockdown or knockout attenuates HCC growth in in vitro and in vivo models. A novel small molecule inhibitor of PGAM5, LFHP-1c, has recently been characterized. [...] Read more.
Background/Objectives: Upregulation of phosphoglycerate mutase 5 (PGAM5) is correlated with reduced survival outcomes in hepatocellular carcinoma (HCC). PGAM5 knockdown or knockout attenuates HCC growth in in vitro and in vivo models. A novel small molecule inhibitor of PGAM5, LFHP-1c, has recently been characterized. The objective of this study was to determine if LFHP-1c effectively reduces HCC viability in cell models. Methods: The hepatoma and HCC cell lines, HepG2 and HuH7, respectively, were treated with LFHP-1c. Label-free imaging was used to quantify growth. Cellular viability and reactive oxygen species (ROS) production were measured using luminescent or fluorescent assays. Expression of antioxidant and metabolic proteins was measured by immunoblot. HepG2 and HuH7 PGAM5 knockout cell lines were used as negative controls. Results: Treatment with LFHP-1c reduced cell growth and viability in HepG2 and HuH7 cell lines. Reactive oxygen species production was upregulated in both wild-type and PGAM5 knockout cell lines following LFHP-1c exposure. Cell viability was reduced following LFHP-1c treatment in PGAM5 knockout cell lines. Conclusions: LFHP-1c reduces hepatoma and HCC viability and enhances ROS production, but these effects are independent of PGAM5. Full article
(This article belongs to the Section Molecular Cancer Biology)
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17 pages, 263 KiB  
Review
The Combined Use of Lenvatinib and Locoregional Therapies for the Management of Hepatocellular Carcinoma
by Ronit Juthani, Pannaga Malalur, Ashish Manne and Arjun Mittra
Cancers 2025, 17(9), 1572; https://doi.org/10.3390/cancers17091572 - 5 May 2025
Viewed by 296
Abstract
Hepatocellular carcinoma (HCC) is a commonly diagnosed malignancy, with the treatment for transplant-ineligible localized disease traditionally relying on locoregional therapies, such as surgical resection, transarterial chemoembolization (TACE), and transarterial radioembolization (TARE). Systemic therapy has historically been reserved for advanced, unresectable HCC. However, lenvatinib, [...] Read more.
Hepatocellular carcinoma (HCC) is a commonly diagnosed malignancy, with the treatment for transplant-ineligible localized disease traditionally relying on locoregional therapies, such as surgical resection, transarterial chemoembolization (TACE), and transarterial radioembolization (TARE). Systemic therapy has historically been reserved for advanced, unresectable HCC. However, lenvatinib, an oral multikinase inhibitor, has recently gained traction as part of a multimodal approach for localized HCC in combination with locoregional treatments. An upfront TACE or TARE can induce tumor hypoxia, leading to the upregulation of hypoxia-inducible factor-1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF), which promotes tumor angiogenesis and progression. The rationale for combining lenvatinib with a locoregional therapy is to enhance tumor shrinkage while preserving liver function before a definitive intervention. Clinical trials, such as TACTICS and LAUNCH, have demonstrated improved outcomes with this approach. Additionally, retrospective studies, including those incorporating immune checkpoint inhibitors, have reported further benefits. This review explores the combination of lenvatinib with various locoregional modalities, including TARE, microwave ablation (MWA), and radiofrequency ablation (RFA), highlighting their indications and clinical outcomes. Furthermore, we discuss the ongoing and upcoming clinical trials investigating the integration of systemic agents with locoregional therapies for intermediate-stage HCC, including EMERALD-1, EMERALD-3, LEAP-012, and CheckMate 74W. Full article
(This article belongs to the Special Issue The Advances in Therapy for Hepatocellular Carcinoma)
15 pages, 1334 KiB  
Systematic Review
Treatment-Related Adverse Events in Extended Stage Small Cell Lung Cancer Patients Receiving First-Line Chemoimmunotherapy Versus Chemotherapy Alone: A Systematic Review and Meta-Analysis
by Elsa Vitale, Alessandro Rizzo, Lorenza Maistrello, Deniz Can Guven, Omar Cauli, Domenico Galetta and Vito Longo
Cancers 2025, 17(9), 1571; https://doi.org/10.3390/cancers17091571 - 5 May 2025
Viewed by 370
Abstract
Introduction: Nowadays the prognosis of extended stage (ES) small cell lung cancer (SCLC) patients is poor. However, a high response rate to first-line chemotherapy (CT) and the addition of immune checkpoint inhibitors (ICIs) have notably ameliorated the outcome of these patients. The aim [...] Read more.
Introduction: Nowadays the prognosis of extended stage (ES) small cell lung cancer (SCLC) patients is poor. However, a high response rate to first-line chemotherapy (CT) and the addition of immune checkpoint inhibitors (ICIs) have notably ameliorated the outcome of these patients. The aim of our study is to compare treatment-related adverse events (TRAEs) between ES- SCLC patients receiving first-line ICIs adding CT and those receiving only CT. Methods: All phase III clinical trials published between 15 June 2008, and 30 June 2024, likenessing ICIs adding systemic CT and only CT in treatment-naïve ES-SCLC patients were retrieved. Results: Twenty-six types of adverse events were included, grouped into ten categories, for a total of 43,391 observations (observations in immune group n = 22,643 and in placebo group n = 20,748) and 9831 events. Our analysis suggested a statistically significant increase in hematological events in patients receiving ICIs plus CT compared with CT alone. Conversely, blood pressure alterations such as hypertension were more frequent in patients treated with CT alone. Conclusions: Despite our analysis confirming the manageable safety profile of chemoimmunotherapy, this remains an issue to be further investigated. Full article
(This article belongs to the Special Issue New Perspectives in the Treatment of Thoracic Cancers)
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20 pages, 7995 KiB  
Article
Reduced HLA-I Transcript Levels and Increased Abundance of a CD56dim NK Cell Signature Are Associated with Improved Survival in Lower-Grade Gliomas
by Md Abdullah Al Kamran Khan, Lorenza Peel, Alexander J. Sedgwick, Yuhan Sun, Julian P. Vivian, Alexandra J. Corbett, Riccardo Dolcetti, Theo Mantamadiotis and Alexander D. Barrow
Cancers 2025, 17(9), 1570; https://doi.org/10.3390/cancers17091570 - 5 May 2025
Viewed by 413
Abstract
Background: Human leukocyte antigen class I (HLA-I) plays a pivotal role in shaping anti-tumour immunity by influencing the functionality of T cells and natural killer (NK) cells within the tumour microenvironment. Methods: Here, we explored the transcriptional landscape of HLA-I molecules across various [...] Read more.
Background: Human leukocyte antigen class I (HLA-I) plays a pivotal role in shaping anti-tumour immunity by influencing the functionality of T cells and natural killer (NK) cells within the tumour microenvironment. Methods: Here, we explored the transcriptional landscape of HLA-I molecules across various solid cancer transcriptomes from The Cancer Genome Atlas (TCGA) database and assessed the impact of HLA-I expression on the clinical significance of tumour-infiltrating CD56dim and CD56bright NK cells. Results: Our analysis revealed that high HLA-I expression correlated with reduced patient survival in the TCGA lower-grade glioma (LGG) cohort, with this association varying by histopathological subtype. We then estimated the relative abundance of 23 immune and stromal cell signatures in LGG transcriptomes using a cellular deconvolution approach, which revealed that LGG patients with low HLA-I expression and high CD56dim NK cell abundance had better survival outcomes compared to those with high HLA-I expression and low CD56dim NK cell abundance. Furthermore, HLA-I expression was positively correlated with various inhibitory NK cell receptors and negatively correlated with activating NK cell receptors, particularly those within the killer cell lectin-like receptor (KLR) gene family. High co-expression of HLA-E and NKG2A predicted poor survival outcomes in LGG patients, whereas low HLA-E and high NKG2C/E abundance predicted more favourable outcomes, suggesting a potential modulatory role of HLA-I on the tumour-infiltrating cytotoxic CD56dim NK cell subset. Conclusions: Overall, our study unveils a potential role for deregulated HLA-I expression in modulating the clinical impact of glioma-infiltrating CD56dim NK cells. These findings lay the foundation for future in-depth experimental studies to investigate the underlying mechanisms. Full article
(This article belongs to the Special Issue NK Cells in the Tumor Microenvironment: Immunosuppressive Mechanisms and Therapy)
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16 pages, 1441 KiB  
Systematic Review
An Updated Meta-Analysis on Long-Term Outcomes Following Hyperthermic Intraperitoneal Chemotherapy in Advanced Ovarian Cancer
by Nadine El Kassis, Myriam Jerbaka, Rime Abou Chakra, Christopher El Hadi, Wissam Arab, Houssein El Hajj, Donal J. Brennan and David Atallah
Cancers 2025, 17(9), 1569; https://doi.org/10.3390/cancers17091569 - 5 May 2025
Viewed by 408
Abstract
Ovarian cancer is the leading cause of death among gynecological malignancies [...] Full article
(This article belongs to the Special Issue Advances in Ovarian Cancer Treatment: Past, Present and Future)
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16 pages, 3003 KiB  
Article
Prognostic Value of LC3A Protein Expression Patterns in Rectal Cancer Tumors
by Vincent Ho, Liping Chung, Tristan Rutland, Vivienne Lea, Stephanie H. Lim, Askar Abubakar, Weng Ng, Mark Lee, Tara L. Roberts, Wei Chua, Scott Mackenzie and Cheok Soon Lee
Cancers 2025, 17(9), 1568; https://doi.org/10.3390/cancers17091568 - 5 May 2025
Viewed by 388
Abstract
Background/Objectives: Autophagy is a conserved self-degradation process by which cells break down and recycle their cellular constituents. This process is activated by various stressors, including nutrient deprivation and DNA damage, and has also been associated with tumor progression. In the present study, [...] Read more.
Background/Objectives: Autophagy is a conserved self-degradation process by which cells break down and recycle their cellular constituents. This process is activated by various stressors, including nutrient deprivation and DNA damage, and has also been associated with tumor progression. In the present study, we aimed to determine the expression patterns, clinicopathological significance, and prognostic value of the autophagy marker microtubule-associated protein 1 light chain 3 alpha (LC3A)—an essential component of autophagic vacuoles—in rectal cancer. Methods: LC3A reactivity was measured by immunohistochemistry in tumor samples from 243 patients who underwent surgery for rectal cancer. Results: Three distinct patterns of LC3A expression were identified: diffuse cytoplasmic, perinuclear, and stone-like structures (SLS). In Kaplan–Meier survival analyses, patients positive for the SLS pattern of LC3A staining in the tumor periphery (TP) had worse overall survival (OS; p = 0.001) and disease-free survival (DFS; p = 0.030) than those without SLSs in this region, as determined by the log–rank test. When patients were stratified by tumor stage, this result was significant in those with stage T3–T4 (OS, p < 0.001; DFS, p = 0.001) but not T1–T2 disease. Multivariate Cox regression analysis further showed an association between TP-localized LC3A SLS positivity and reduced OS for the overall cohort (hazard ratio [HR] = 2.6313, 95% confidence interval [CI]: 1.090–6.349, p = 0.031) and specifically those in the T3–T4 subgroup (HR = 3.347, 95% CI: 1.657–6.760, p = 0.001). Conclusions: Our findings suggest that positivity for SLSs in the TP may hold clinical value as a biomarker for survival prognosis in rectal cancer patients. Full article
(This article belongs to the Special Issue The Role of Apoptosis and Autophagy in Cancer)
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14 pages, 2244 KiB  
Article
CDK4/6 Inhibitors-Induced Macrocytosis Is Not Associated with Hemolysis and Does Not Impact Hemoglobin Homeostasis
by Tiago Barroso, Leila Costa, Lisa Gonçalves, Vanessa Patel, João Araújo, Inês Pinho, Carolina Monteiro, Miguel Esperança-Martins, Catarina Abreu, Rita Teixeira de Sousa, Helena Pais, Gonçalo Nogueira-Costa, Sofia Torres, Leonor Abreu Ribeiro and Luís Marques da Costa
Cancers 2025, 17(9), 1567; https://doi.org/10.3390/cancers17091567 - 5 May 2025
Viewed by 308
Abstract
Background: CDK 4/6 inhibitors (CDK4/6is) are the first-line treatment for metastatic luminal-like breast cancer (BC). These drugs induce macrocytosis without anemia in most patients. The mechanism for the red blood cell (RBC) changes is unknown. In vitro and animal studies show that RBCs [...] Read more.
Background: CDK 4/6 inhibitors (CDK4/6is) are the first-line treatment for metastatic luminal-like breast cancer (BC). These drugs induce macrocytosis without anemia in most patients. The mechanism for the red blood cell (RBC) changes is unknown. In vitro and animal studies show that RBCs from CDK6-knockout mice have increased membrane fragility, but the clinical impact of CDK4/6is on human RBC lifespan is not known. We sought to determine the impact of CDK4/6is on RBC lifespan and detect changes in the regulation of hemoglobin production. Using the mean corpuscular volume (MCV) measurements at several time points, we can study the evolution of MCV, mean corpuscular hemoglobin concentration (MCHC), and RBC count over time. From this, one can estimate the RBC lifespan under CDK4/6is. Methods: We performed a unicentric retrospective study. Based on published models of RBC population dynamics, we have coded a biologically inspired model which allowed us to extract values for biological parameters, including the RBC lifespan. Results: A total of 122 patients were identified, and 1959 laboratory measurements were analyzed. After the pre-treatment RBCs were replaced, the mean MCV increased by 12.6 femtoliter (fL) (95% Bayesian credible interval [CdI] 13–14), the MCHC increased slightly by 0.69 g/dL (95% CdI 0.42–0.96), and the RBC count decreased by 0.77 × 109/L (95% CdI 0.42 × 109/L–0.96 × 109/L). The net result was a 0.64 g/dL (95% CdI 0.48–0.80) rise in hemoglobin. The mean total RBC lifetime was 118 days (95% CdI 114–122), similar to the value measured in healthy persons. Discussion and Conclusions: These findings suggest that, despite changes in RBC volume, CDK4/6is do not predispose patients to RBC destruction and do not impair regulation of hemoglobin homeostasis. We show that CDK4/6is do not decrease the RBC lifespan in pre-treatment erythrocytes. Unfortunately, this method cannot determine the lifespan of post-treatment RBCs, but further research could help answer this question. Full article
(This article belongs to the Special Issue The Role of Aromatase Inhibitors in Breast Cancer Treatment)
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Review
The Molecular Basis of Pediatric Brain Tumors: A Review with Clinical Implications
by Elias Antoniades, Nikolaos Keffes, Stamatia Vorri, Vassilios Tsitouras, Nikolaos Gkantsinikoudis, Parmenion Tsitsopoulos and John Magras
Cancers 2025, 17(9), 1566; https://doi.org/10.3390/cancers17091566 - 4 May 2025
Viewed by 464
Abstract
Central nervous system (CNS) tumors are the most common solid malignancy in the pediatric population. These lesions are the result of the aberrant cell signaling step proteins, which normally regulate cell proliferation. Mitogen-activated protein kinase (MAPK) pathways and tyrosine kinase receptors are involved [...] Read more.
Central nervous system (CNS) tumors are the most common solid malignancy in the pediatric population. These lesions are the result of the aberrant cell signaling step proteins, which normally regulate cell proliferation. Mitogen-activated protein kinase (MAPK) pathways and tyrosine kinase receptors are involved in tumorigenesis of low-grade gliomas. High-grade gliomas may carry similar mutations, but loss of epigenetic control is the dominant molecular event; it can occur either due to histone mutations or inappropriate binding or unbinding of DNA on histones. Therefore, despite the absence of genetic alteration in the classic oncogenes or tumor suppressor genes, uncontrolled transcription results in tumorigenesis. Isocitric dehydrogenase (IDH) mutations do not predominate compared to their adult counterpart. Embryonic tumors include medulloblastomas, which bear mutations of transcription-regulating pathways, such as wingless-related integration sites or sonic hedgehog pathways. They may also relate to high expression of Myc family genes. Atypical teratoid rhabdoid tumors harbor alterations of molecules that contribute to ATP hydrolysis of chromatin. Embryonic tumors with multilayered rosettes are associated with microRNA mutations and impaired translation. Ependymomas exhibit great variability. As far as supratentorial lesions are concerned, the major events are mutations either of NFkB or Hippo pathways. Posterior fossa tumors are further divided into two types with different prognoses. Type A group is associated with mutations of DNA damage repair molecules. Lastly, germ cell tumors are a heterogeneous group. Among them, germinomas manifest KIT receptor mutations, a subgroup of the tyrosine kinase receptor family. Full article
(This article belongs to the Special Issue New Advances in the Treatment of Pediatric Solid Tumors)
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