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Cancers, Volume 17, Issue 15 (August-1 2025) – 5 articles

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15 pages, 2893 KiB

Open AccessArticle

NRP1 and GFAP Expression in the Medulloblastoma Microenvironment: Implications for Angiogenesis and Tumor Progression

by Margarita Belem Santana-Bejarano, María Paulina Reyes-Mata, José de Jesús Guerrero-García, Daniel Ortuño-Sahagún and Marisol Godínez-Rubí

Cancers 2025, 17(15), 2417; https://doi.org/10.3390/cancers17152417 (registering DOI) - 22 Jul 2025

Abstract

Background/Objectives: Medulloblastoma (MB) is the second leading cause of cancer-related death in children. Its tumor microenvironment (TME) includes endothelial, glial, and immune cells that influence tumor architecture and progression. Neuropilin-1 (NRP1), a co-receptor for semaphorins and vascular endothelial growth factor (VEGF), is expressed in various cell types during oncogenesis, yet its role in MB progression remains unclear. This study aimed to evaluate the expression and localization of NRP1 and glial fibrillary acidic protein (GFAP) in MB tissue. Methods: We analyzed MB tissue samples using immunohistochemistry, immunofluorescence, and quantitative PCR. Samples were stratified by molecular subgroup (WNT, SHH, non-WNT/non-SHH). We assessed NRP1 expression in tumor-associated microglia/macrophages (TAMs) and endothelial cells, as well as GFAP expression in astrocytes and tumor cells. Histopathological correlations and survival analyses were also conducted. Results: NRP1 was consistently expressed by TAMs across all MB molecular subgroups. Tumor vasculature showed strong endothelial NRP1 expression, while perivascular astrocytic coverage was frequently absent. Astrocytic processes exhibited spatial differences according to tumor histology. In SHH-MBs, a subset of tumor cells showed aberrant GFAP expression, which correlated with tumor recurrence or progression. Conclusions: NRP1 and GFAP display distinct expression patterns within the MB microenvironment, reflecting subgroup-specific biological behavior. Endothelial NRP1 positivity combined with limited vascular-astrocytic interaction and aberrant GFAP expression in SHH-MB may contribute to dysregulated angiogenesis and tumor progression. These findings warrant further investigation to explore their prognostic and therapeutic implications. Full article

(This article belongs to the Special Issue Cellular and Molecular Mechanisms of Malignant Nervous System Cancers)

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18 pages, 482 KiB

Open AccessArticle

Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer: Evaluation of Sequencing, Response, and Toxicity in a Single-Institution Cohort

by Maria Cristina Barba, Paola De Franco, Donatella Russo, Elisa Cavalera, Elisa Ciurlia, Sara De Matteis, Giuseppe Di Paola, Corradino Federico, Angela Leone, Antonella Papaleo, Bianca Santo, Dino Rubini, Giuseppe Rubini and Angela Sardaro

Cancers 2025, 17(15), 2416; https://doi.org/10.3390/cancers17152416 (registering DOI) - 22 Jul 2025

Abstract

Background: Total neoadjuvant therapy (TNT) has emerged as a promising strategy for locally advanced rectal cancer (LARC). By administering both chemoradiotherapy (CRT) and systemic chemotherapy (CHT) pre-surgery, TNT is associated with improved disease-free survival (DFS), reduced distant metastases, and higher pathological complete response (pCR) rates. Materials and Methods: This study included patients with LARC who received various TNT schedules: induction chemotherapy (iCHT), consolidation chemotherapy (cCHT), or a combination of both (sandwichCHT). We analyzed treatment adherence, toxicity, and pathological response. Local and distant disease recurrence, as well as survival outcomes, were also evaluated. Results: Between May 2021 and January 2025, 70 patients received TNT. Treatment included iCHT (41%), sandwichCHT (49%), and cCHT (10%). Most patients (94%) received long-course radiotherapy (LCRT). Overall, TNT was well tolerated, with grade 2 gastrointestinal toxicity during CRT being the most common frequent adverse event (33%). Disease progression during TNT was noted in five patients (7%); three of these patients were receiving chemotherapy, while two underwent surgical resection of the primary tumor. A watch-and-wait strategy was adopted for five patients (7%) following TNT. Surgical procedures performed included anterior resection (92%), abdominoperineal resection (7%), and local excision (1%). Pathological assessment revealed an overall pCR rate of 30%. With a median follow-up of 17 months, no patients experienced local recurrence. Post-surgery, 10 patients (17%) developed disease progression. The median DFS was 14.7 months. Five patients (7%) died during the follow-up period, with only one death attributed to causes other than disease progression. Conclusions: In this cohort of LARC patients, TNT demonstrated favorable tolerability and encouraging short-term efficacy. Full article

(This article belongs to the Section Cancer Pathophysiology)

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16 pages, 574 KiB

Open AccessReview

Advances in Vulvar Cancer: A Radiation Oncology Perspective

by Diandra N. Ayala-Peacock and Manjeet Chadha

Cancers 2025, 17(15), 2415; https://doi.org/10.3390/cancers17152415 (registering DOI) - 22 Jul 2025

Abstract

Despite being a rare malignancy, there have been several changes in the management paradigm for vulvar cancer. This review of the literature was undertaken to highlight key areas of treatment innovation and progress, including efforts to de-escalate morbid surgical resection as well as perform dose escalation of radiotherapy and incorporation of modern systemic agents to achieve better oncologic outcomes. There is still much debate regarding key high-risk pathology features and their corresponding prognostic significance and indications for adjuvant treatments. However, we are also developing a more nuanced understanding of the importance of precursor lesions and resultant subtypes of vulvar cancer, which suggests that there are more subtypes beyond the umbrella distinction of HPV status. Moving forward, we anticipate there will be an increasing number of trials investigating the triaging of management recommendations based on risk. Full article

(This article belongs to the Special Issue Advances in Vulvar Cancer)

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16 pages, 1413 KiB

Open AccessArticle

Predicting Cardiovascular Risk in Patients with Prostate Cancer Receiving Abiraterone or Enzalutamide by Using Machine Learning

by Dong-Yi Chen, Chun-Chi Chen, Ming-Lung Tsai, Chieh-Yu Chang, Ming-Jer Hsieh, Tien-Hsing Chen, Po-Jung Su, Pao-Hsien Chu, I-Chang Hsieh, See-Tong Pang and Wen-Kuan Huang

Cancers 2025, 17(15), 2414; https://doi.org/10.3390/cancers17152414 (registering DOI) - 22 Jul 2025

Abstract

Purpose: The identification of cardiovascular risk factors in metastatic prostate cancer (PCa) patients prior to the initiation of androgen receptor pathway inhibitors (ARPIs) is important yet challenging. Methods and Results: A nationwide cohort study was conducted utilizing data from the National Health Insurance Research Database containing the Taiwan Cancer Registry. The study population comprised 4739 PCa patients who received abiraterone or enzalutamide between 1 January 2014, and 28 February 2022. The cohort was divided into a training set (n = 3318) and a validation set (n = 1421). Machine learning techniques with random survival forest (RSF) model incorporating 16 variables was developed to predict major adverse cardiovascular events (MACEs). Over a mean follow-up period of 2.1 years, MACEs occurred in 10.9% and 11.3% of the training and validation cohorts, respectively. The RSF model identified five key predictive indicators: age < 65 or ≥75 years, heart failure, stroke, hypertension, and myocardial infarction. The model exhibited robust performance, achieving an area under the curve (AUC) of 85.1% in the training set and demonstrating strong external validity with an AUC of 85.5% in the validation cohort. A positive correlation was observed between the number of risk factors and the incidence of MACEs. Conclusions: This machine learning approach identified five predictors of MACEs in PCa patients receiving ARPIs. These findings highlight the need for comprehensive cardiovascular risk assessment and vigilant monitoring in this patient population. Full article

(This article belongs to the Special Issue Quality of Life and Side Effects Management in Cancer Treatment (3rd Edition))

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18 pages, 982 KiB

Open AccessArticle

Cardiotoxicity in Adult Patients with Relapsed or Refractory Acute Myeloid Leukemia

by Laura Torres-Miñana, Blanca Boluda, Antonio Solana-Altabella, Rebeca Rodríguez-Veiga, Isabel Cano, Evelyn Acuña-Cruz, Irene Navarro-Vicente, Pilar Lloret-Madrid, Paulina Hillebrand, David Martínez-Campuzano, Ana Osa-Sáez, Jaume Aguero, Yolanda Mendizábal, Beatriz Martín-Herreros, Eva Barragán, Claudia Sargas, Cristina Gil, Carmen Botella, Lorenzo Algarra, José Santiago Bermon, Raimundo García Boyero, María José Sayas, Mar Tormo, Aurelio López, Marta Valero-Nuñez, Marisa Calabuig, Javier De la Rubia, David Martínez-Cuadrón and Pau Montesinos Show full author list Hide full author list

Cancers 2025, 17(15), 2413; https://doi.org/10.3390/cancers17152413 (registering DOI) - 22 Jul 2025

Abstract

Background/Objectives: The incidence of cardiac morbimortality in patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) is unknown. Methods: We analyze the characteristics, incidence, risk factors, and outcomes of cardiac events in AML patients treated for second-line (2L) or third-line (3L) episodes. Results: Among 327 2L AML patients (median age 62 years old), 135 experienced cardiac events, with an incidence of 38.6% non-fatal and 1.3% fatal events at 6 months. The grade 1–2 incidence was 16.8%, and the grade 3–4 incidence was 23.5% at 6 months. Overall, 207 cardiac events occurred in the 2L cohort, the most frequent being hypertension (n = 45), bradycardia (n = 39), QTc prolongation (n = 35), heart failure (n = 33), syncope/presyncope (n = 22), arrhythmia (n = 18), and myocardial ischemia (n = 8). Median OS in the 2L cohort was 9.4 months, 21.4 months in patients with grade 1–2, 8.8 months in patients without a cardiac event, 7.6 months in grade 3–4 patients, and 2.1 months with in 5 patients (p = 0.0035). The multivariate analysis showed prior cardiologic antecedents (p = 0.013), intensive 2L chemotherapy (p = 0.01), and inclusion in a 2L clinical trial (p < 0.001) as independent risk factors for non-fatal cardiac events. Among 189 patients of the 3L cohort, the incidence of non-fatal and fatal cardiac events was 49.2% and 0% at 6 months, respectively. Non-fatal cardiac events were more frequent in patients with prior cardiac antecedents (p = 0.004). Conclusions: In summary, cardiotoxicity is a frequent and challenging complication in R/R AML patients. We identified the risk factors that could be relevant to implementing risk-adapted management guidelines, aiming to reduce morbi-mortality in this difficult-to-treat setting. Full article

(This article belongs to the Collection Acute Myeloid Leukemia (AML))

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