Oncology Reviews最新文献

{"title":"Occult squamous cell carcinoma presenting as oligometastatic lymphadenopathy. A systematic review with a case report.","authors":"Łukasz Ważny, Jakub Ciesielka, Krzysztof Jakimów, Aleksandra Tobiasz, Paulina Kluszczyk, Grzegorz Owczarek, Mateusz Winder, Jerzy T Chudek","doi":"10.3389/or.2026.1801426","DOIUrl":"10.3389/or.2026.1801426","url":null,"abstract":"<p><strong>Background: </strong>An occult squamous cell carcinoma (SCC) is a rare subtype of SCC for which standard radiological protocols are often unable to identify the primary tumour. We describe our patient's history and provide a systematic review of the literature.</p><p><strong>Objectives: </strong>To review the clinical characteristics, treatment strategies, and outcomes of patients with occult SCC presenting with lymph node (LN) metastases and to report a rare case of a patient with occult SCC metastasizing to the inguinal and iliac LNs.</p><p><strong>Methods: </strong>A systematic literature search was conducted in PubMed, Scopus, and Embase, covering the period from 2000 to 2025. The inclusion criteria for eligible studies comprised case reports and case series documenting patients with occult SCC presenting with LN metastases. Data were extracted at the individual-patient level and synthesised descriptively. A 75-year-old man suffering from myelodysplastic syndrome presented with inguinal lymphadenopathy. Pathological analysis of a core needle biopsy revealed metastases of poorly differentiated SCC. Positron emission tomography-computed tomography (18F-fluorodeoxyglucose PET-CT) showed isolated glucose uptake in the iliac LNs without a potential site of primary disease. Consequently, an iliac lymphadenectomy was performed, followed by adjuvant radiotherapy. The patient remained asymptomatic with no signs of cancer for 15 months following treatment; however, follow-up PET-CT imaging revealed retroperitoneal lymphatic recurrence.</p><p><strong>Results: </strong>Metastases to cervical LNs were observed in a significantly higher proportion of males than of females (63.4% vs. 39.5%; p = 0.033). On the contrary, inguinal LN metastases were more frequently observed in females than in males (39.5% vs. 17.1%; p = 0.026). Within the assessed cohort, systemic therapy was administered to 62% of patients, radiotherapy to 68.4%, and surgical intervention to 59.5%. Notably, five patients (6.3%) received immunotherapy.</p><p><strong>Conclusion: </strong>The diversity of therapeutic approaches documented in the literature emphasizes the importance of individualised treatment strategies, including immunotherapy. Genomic profiling may help implement molecular-based therapy; however, no genetic testing has been reported for the patients included in this cohort.</p>","PeriodicalId":19487,"journal":{"name":"Oncology Reviews","volume":"20 ","pages":"1801426"},"PeriodicalIF":4.0,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13447356/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148689585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Models of high-grade serous carcinoma of tubo-ovarian origin.","authors":"Achuth Padmanabhan, Shailendra Dwivedi, Melissa A Merritt, Priyanka Verma, Ronald J Buckanovich, Jessica D Lang, Hannah Dimmick, Kenneth P Nephew, Ronny Drapkin, Lindsay W Brubaker, Benjamin G Bitler","doi":"10.3389/or.2026.1849834","DOIUrl":"10.3389/or.2026.1849834","url":null,"abstract":"<p><p>Biological models aim to recapitulate the molecular and histologic characteristics, as well as the carcinogenesis of the disease of interest, to enable high-fidelity experimentation and impactful translational development. In high-grade serous carcinoma of ovarian, tubal, or peritoneal origin, there is a need to regularly re-evaluate the experimental models being employed to address research questions. This review aims to provide a resource for better understanding the applications, strengths, and limitations of the available models. This work discusses the origin and carcinogenesis of high-grade serous carcinoma and reviews normal cell-of-origin models, as understanding the cellular origin is critical to experimental efforts focused on pathogenesis, disease progression, and prevention. High-grade serous carcinoma cell lines are discussed, including essential and complementary molecular features, cell line management, and limitations. Next, the review examines advances in organoids, with a specific focus on patient-derived organoids from ascites and single-cell suspensions, organ-on-a-chip platforms, and tissue slice technologies. Finally, given the heterogeneity of epithelial ovarian cancer in general, and high-grade serous carcinoma in particular, and the evolving understanding of the importance of the tumor microenvironment, <i>in vivo</i> models capture organism-level complexity. In this review, we focused on high-grade serous carcinoma. In this context, we review patient-derived xenograft (PDX), syngeneic, and genetically engineered mouse models. Each has its own advantages and disadvantages, and guidance is provided on the optimal use of these <i>in vivo</i> approaches for the study of high-grade serous carcinoma.</p>","PeriodicalId":19487,"journal":{"name":"Oncology Reviews","volume":"20 ","pages":"1849834"},"PeriodicalIF":4.0,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13416685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148620908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PSMA-targeted radioligand therapy in advanced prostate cancer: a narrative review of ^177Lu-PSMA, emerging ^225Ac-PSMA strategies, and therapeutic sequencing.","authors":"Natalia Gierulska, Nina Jankowska, Adrianna Kwiatkowska, Piotr Kuchno, Kinga Łysak, Katarzyna Szklener, Kamil Kośmider, Magdalena Skórzewska","doi":"10.3389/or.2026.1834484","DOIUrl":"10.3389/or.2026.1834484","url":null,"abstract":"<p><p>Prostate cancer remains a leading cause of cancer-related morbidity and mortality among men, and metastatic castration-resistant prostate cancer continues to present substantial therapeutic challenges despite advances in androgen receptor pathway inhibitors, taxane chemotherapy, PARP inhibitors, and immunotherapy for selected molecular subgroups. Prostate-specific membrane antigen (PSMA)-targeted radioligand therapy has emerged as a clinically important theranostic strategy that combines molecular imaging-based patient selection with targeted delivery of cytotoxic radiation to PSMA-expressing tumor sites. This narrative review summarizes the biological rationale, clinical evidence, safety profile, and evolving treatment-sequencing considerations for PSMA-targeted radioligand therapy in advanced prostate cancer. Particular emphasis is placed on ^177Lu-PSMA-617, which has demonstrated improved radiographic progression-free survival and overall survival in pivotal randomized trials, including VISION, TheraP, and PSMAfore. The review also examines investigational alpha-emitting PSMA-targeted therapies, particularly ^225Ac-PSMA compounds, which offer high-linear-energy-transfer cytotoxicity and may have activity in selected patients after progression on beta-emitting radioligand therapy, although definitive phase III evidence remains lacking. The established bone-targeted alpha-emitter ^223Ra is discussed separately as contextual therapy for selected patients with symptomatic bone-predominant mCRPC without visceral metastases. As clinical use of radioligand therapy expands, optimization of PSMA PET-based patient selection, management of salivary, hematologic, and renal toxicities, sequencing with other systemic therapies, and integration into multidisciplinary care pathways will be essential. Future research should prioritize randomized clinical trials, individualized dosimetry, predictive biomarkers, toxicity mitigation, and patient-centered implementation strategies.</p>","PeriodicalId":19487,"journal":{"name":"Oncology Reviews","volume":"20 ","pages":"1834484"},"PeriodicalIF":4.0,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13416105/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148620957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recurrent retroperitoneal sarcoma: beyond resectability toward a biology-based therapeutic framework.","authors":"Dorian Yarih Garcia-Ortega, Montiel Jiménez Fuertes, Sergio Damian Quildrian, Nicolas A Devaud, Javier Martin-Broto","doi":"10.3389/or.2026.1846525","DOIUrl":"10.3389/or.2026.1846525","url":null,"abstract":"<p><p>Recurrent retroperitoneal sarcoma remains a significant therapeutic challenge. Recurrence does not always indicate treatment failure but reflects different tumor biologies with diverse implications for local and systemic management. This review proposes a biology-based framework for recurrent RPS that incorporates histology, disease-free interval, tumor growth kinetics, multifocality, resectability, functional reserve, and therapeutic proportionality. Histological subtype significantly influences recurrence patterns. Well-differentiated liposarcoma often follows a chronic local-regional course, where multiple surgeries can offer long-term control. In contrast, leiomyosarcoma more commonly shows early systemic spread, which diminishes the benefit of repeated local treatments. Disease-free interval and tumor growth rate are important dynamic indicators that improve prognosis and assist in timing treatment. Complete resection is essential for a meaningful survival benefit, but resectability alone does not justify surgery. Radiotherapy and systemic therapy serve complementary roles, mainly in local control, biological modulation, and palliation. Prognostic tools and nomograms aid in initial risk assessment, but are most valuable when combined with dynamic factors that reflect tumor behavior. Future advancements will rely on clinically relevant biomarkers, adaptive predictive models, personalized surveillance, recurrence-focused clinical trials, and shared decision-making based on meaningful patient benefits.</p>","PeriodicalId":19487,"journal":{"name":"Oncology Reviews","volume":"20 ","pages":"1846525"},"PeriodicalIF":4.0,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13416250/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148620952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Salivary cell-free DNA in head and neck cancer: emerging clinical applications and future perspectives.","authors":"Vaishnavi N Patel, Aditi B Patel, Shreya A Lotia, Vivek M Tanavde, Shanaya S Patel","doi":"10.3389/or.2026.1885622","DOIUrl":"10.3389/or.2026.1885622","url":null,"abstract":"<p><p>Head and neck cancer (HNC) diagnosis and surveillance still rely primarily on clinical examination, imaging, and tissue biopsy, with no established non-invasive biomarkers for routine early detection or disease monitoring. This limitation underscores the need for alternative strategies that can facilitate timely diagnosis and longitudinal assessment. Salivary cell-free DNA (scfDNA) has emerged as a promising liquid biopsy biomarker owing to its close proximity to primary HNC lesions and its suitability for non-invasive, repeatable sampling. Detection and characterization of scfDNA enable the identification of tumour-associated molecular alterations, including somatic mutations, aberrant DNA methylation, copy number alterations, viral DNA, and fragmentation signatures, providing valuable insights into tumour biology and disease dynamics. These molecular features have demonstrated considerable potential for early detection, prognostication, therapeutic monitoring, and post-treatment surveillance in head and neck cancer. However, current data are derived largely from exploratory studies with heterogeneous methodologies, small validation cohorts, and limited standardization of analytical workflows. Nevertheless, advances in sample processing, extraction methods, high-sensitivity sequencing technologies, and advanced bioinformatic approaches are enhancing assay accuracy and reproducibility. This review summarizes the current evidence on scfDNA in HNC by delineating its biological basis, evaluating the robustness and translational relevance of available clinical studies, and examining the analytical, technical, and implementation challenges that must be addressed to facilitate its integration into evidence-based clinical practice.</p>","PeriodicalId":19487,"journal":{"name":"Oncology Reviews","volume":"20 ","pages":"1885622"},"PeriodicalIF":4.0,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13395914/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148584909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative efficacy of subsequent-line therapies for advanced triple-negative breast cancer: a bayesian network meta-analysis.","authors":"Zheng Xu, Linxian Ding, Tai Zhao, Zhoumin Xu","doi":"10.3389/or.2026.1834466","DOIUrl":"10.3389/or.2026.1834466","url":null,"abstract":"<p><strong>Background: </strong>Direct head-to-head randomized comparisons among emerging therapies are limited, making it difficult to determine the optimal subsequent-line treatment for advanced triple-negative breast cancer (TNBC). This study aimed to systematically compare the relative efficacy of second- and later-line regimens using a Bayesian network meta-analysis (NMA).</p><p><strong>Methods: </strong>PubMed, Embase, Web of Science, Cochrane Library and ClinicalTrials.gov were searched to 30 September 2025 for randomized controlled trials (RCTs) of second-/later-line advanced TNBC. A Bayesian NMA estimated effects on objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). SUCRA was used for ranking, and model convergence was assessed by Gelman-Rubin diagnostics. Single-arm studies were included only in sensitivity analyses using a down-weighted binomial model for ORR. Additional sensitivity analyses included ChemoC node splitting and evidence certainty assessment (CINeMA).</p><p><strong>Results: </strong>Thirty-one RCTs and 34 single-arm studies (11,048 patients; 22 regimens) were included. Antibody-drug conjugate (ADC)-based therapies showed the most favorable efficacy overall. Sacituzumab govitecan (SG), sacituzumab tirumotecan (ST), and trastuzumab deruxtecan (T-DXd) ranked highest for ORR and PFS, with consistent benefits for SG and ST versus chemotherapy. T-DXd showed benefit mainly in HER2-low, HR-negative patients. For OS, SG and ST demonstrated clear advantages, while T-DXd showed non-significant effects. Combination chemotherapy outperformed single-agent chemotherapy for ORR and PFS. PARP inhibitors and PD-1-based regimens showed inconsistent efficacy across outcomes. Sensitivity analyses confirmed that incorporating single-arm data and separating chemotherapy nodes did not materially change treatment rankings or overall conclusions.</p><p><strong>Conclusion: </strong>ADCs, particularly SG and ST, were generally associated with favorable efficacy across outcomes in the subsequent-line treatment of advanced TNBC. These results may support clinical decision-making, although heterogeneity in study populations and the absence of direct comparisons highlight the need for further head-to-head trials.</p>","PeriodicalId":19487,"journal":{"name":"Oncology Reviews","volume":"20 ","pages":"1834466"},"PeriodicalIF":4.0,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13391881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148579562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting glucocorticoid receptor signaling in platinum-resistant ovarian cancer: translational rationale and clinical advances following the ROSELLA trial.","authors":"Wenxiang Wang, Zhanghuan Li, Junjie Zhao, Mengyuan Chang, Yafang Zhang, Xiangyi Shen, Junming Yue, John Schorge, Wenjing Zhang","doi":"10.3389/or.2026.1861081","DOIUrl":"10.3389/or.2026.1861081","url":null,"abstract":"<p><p>Platinum-resistant ovarian cancer (PROC) remains a major clinical challenge, with limited effective treatment options and poor survival outcomes. Aberrant activation of the glucocorticoid receptor (GR) signaling pathway promotes tumor progression, chemoresistance, and immune evasion, providing a strong rationale for therapeutic targeting. Selective GR antagonists (SGRAs) represent an emerging novel strategy aimed at blocking this pro-tumorigenic pathway while minimizing off-target effects. Preclinical studies demonstrated that GR blockade restores chemosensitivity, particularly to taxane-based therapies, and may modulate the tumor microenvironment. These findings have translated into clinical evaluation, culminating in the phase 3 ROSELLA trial, which reported that the addition of relacorilant, a SGRA, to nab-paclitaxel significantly improved progression-free and overall survival in patients with recurrent PROC. These results, presented in March 2026, establish GR antagonism as a promising therapeutic strategy and a potential new treatment paradigm in this setting. In this evidence-based review, we summarize the biological basis of GR signaling in ovarian cancer, evaluate the clinical evidence supporting SGRAs, and discuss key challenges for implementation, including biomarker development, safety considerations, and rational combination strategies with chemotherapy, PARP inhibitors, and immunotherapy. We also highlight critical considerations for future clinical trial design to optimize the integration of GR-targeted therapies into the management of ovarian cancer.</p>","PeriodicalId":19487,"journal":{"name":"Oncology Reviews","volume":"20 ","pages":"1861081"},"PeriodicalIF":4.0,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13391958/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148579639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nature-based physical activity in breast cancer survivors: a new frontier in supportive care.","authors":"Giuditta Carretti, Mirko Manetti, Mirca Marini","doi":"10.3389/or.2026.1837259","DOIUrl":"10.3389/or.2026.1837259","url":null,"abstract":"<p><p>Breast cancer (BC) survivors frequently experience long-term physical and psychosocial sequelae following treatment, including cancer-related fatigue, cardiovascular dysfunction, sarcopenia, sleep disturbances, and emotional distress, which can significantly affect quality of life. Structured physical activity is widely recognized as a key component of supportive oncology care and has demonstrated benefits in improving physical function, psychological wellbeing, and survival outcomes. However, adherence to exercise recommendations remains suboptimal in cancer patients mostly due to treatment-related symptoms, motivational barriers, and limited access to tailored supervised programs. Though the field remains relatively underexplored within exercise oncology, nature-based physical activity (NBPA), defined as exercise performed in natural environments, is emerging as a promising complementary approach that integrates the physiological benefits of physical exercise with the restorative effects of nature exposure. Growing evidence indicates that natural settings can support stress reduction, autonomic regulation, immune function, and psychological resilience, potentially enhancing the overall benefits of physical activity. Several effects have been documented in broader populations and, to a lesser degree, among cancer survivors, while direct evidence specifically addressing BC survivors remains limited. Therefore, many of the proposed psychophysiological mechanisms should currently be regarded as plausible and biologically supported hypotheses requiring further validation through dedicated clinical studies. This perspective paper synthesizes current evidence on the role of NBPA in BC survivorship by discussing the psychophysiological mechanisms underlying health effects of nature exposure in this vulnerable population and the main investigated outdoor activities, including walking and Nordic walking, aquatic disciplines, green mind-body practices, and forest-based programs. Finally, the article highlights research gaps and future directions aiming at providing concrete hints to stably integrate nature-based interventions into multidisciplinary survivorship care pathways addressing BC survivors.</p>","PeriodicalId":19487,"journal":{"name":"Oncology Reviews","volume":"20 ","pages":"1837259"},"PeriodicalIF":4.0,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13388476/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148562692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autophagy in thyroid cancer: stage-dependent switch, mutation-specific regulation, and therapeutic targeting.","authors":"Lihua Fang, Chaowen Wu, Huimin Sun, Jie Ning","doi":"10.3389/or.2026.1873752","DOIUrl":"10.3389/or.2026.1873752","url":null,"abstract":"<p><p>Autophagy plays context-dependent roles in thyroid cancer, but whether its dual nature represents a reversible balance or an irreversible stage-dependent switch has remained unclear. This review synthesizes evidence across papillary, follicular, medullary, and anaplastic thyroid carcinoma subtypes and reveals that the transition from tumor-suppressive to tumor-promoting autophagy is unidirectional and driven by disease progression, not a simultaneous equilibrium. The major driver mutations BRAF V600E, RAS, and RET regulate autophagy through distinct mechanisms, demanding subtype-specific therapeutic strategies rather than a uniform approach. Importantly, autophagy is an adaptive resistance mechanism rather than a primary driver, as no thyroid cancer is driven by mutations in autophagy genes. Consequently, autophagy inhibitors will not work as monotherapy but may sensitize tumors to standard treatments that create therapeutic stress. Current clinical translation remains stalled by poor inhibitor specificity, lack of validated biomarkers, and unknown treatment timing. We conclude that the field should move from descriptive studies to biomarker-enriched, hypothesis-driven trials, prioritizing anaplastic thyroid carcinoma for hydroxychloroquine-TKI combinations while standardizing assays for p62 and LC3B to enable patient selection.</p>","PeriodicalId":19487,"journal":{"name":"Oncology Reviews","volume":"20 ","pages":"1873752"},"PeriodicalIF":4.0,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13388884/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148562724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting notch signaling pathway in esophageal cancer: from molecular insights to therapies.","authors":"Sangita Bhattacharyya, Hindole Ghosh, Ameer Hamza, Bernhard Biersack, Gregory N Gan, Prateek Sharma, Prasad Dandawate","doi":"10.3389/or.2026.1709219","DOIUrl":"10.3389/or.2026.1709219","url":null,"abstract":"<p><p>Esophageal cancer (EC) is a major digestive cancer with a poor 5-year survival rate of less than 20%. EC incidence is projected to increase by 35% in the US by 2025. The two subtypes of EC with distinct histology, esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC), exhibit deregulation of various oncogenic signaling pathways, distinct pathological features at diagnosis, and distinct mutation profiles. Hence, these cancers require different treatment approaches for their clinical management. ESCC is more prevalent globally, while EAC is prevalent in Western countries, including Europe, North America, and Australia. Notably, two-thirds of US EC cases are EAC. Drug resistance, faster progression, and recurrence are significant problems of EC. Hence, there is a need to identify novel targets in EC progression. Cancer stem cells (CSCs) are a small population of cells in tumors that can self-renew and are responsible for EMT, drug resistance, and recurrence in EC. These serve as attractive targets for drug development and EC treatment. CSCs express surface markers and use the notch, Hedgehog, Hippo, and Wnt-β-catenin pathways to regulate their growth and survival. We are also including a mutation and expression analysis of PANCAN and EC patients for genes/proteins in the notch signaling pathway, using the cBioPortal and TCGA databases. EC was ranked second among cancers with mutations in the notch pathway. Here, we outline the role of notch signaling in EC biology and its inhibitors for EC treatment.</p>","PeriodicalId":19487,"journal":{"name":"Oncology Reviews","volume":"20 ","pages":"1709219"},"PeriodicalIF":4.0,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13388543/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148562720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}