Cancer treatment reviews最新文献

{"title":"Glioblastoma and resistance to radiotherapy: role of cancer stem cells subpopulations, hypoxia and therapeutic strategies","authors":"Elsa Sarrazin,&nbsp;Samuel Valable,&nbsp;Elodie A. Pérès,&nbsp;Nathalie Colloc'h,&nbsp;Evelyne Emery,&nbsp;Paul Lesueur,&nbsp;Arthur Leclerc,&nbsp;Myriam Bernaudin,&nbsp;Juliette Aury-Landas","doi":"10.1016/j.ctrv.2026.103198","DOIUrl":"10.1016/j.ctrv.2026.103198","url":null,"abstract":"<div><div>Glioblastoma is the most aggressive primary brain tumor in adults, characterized by rapid progression, resistance to therapy, and inevitable recurrence. Despite standard treatment—surgical resection, X-ray radiotherapy, and temozolomide chemotherapy—prognosis remains poor. Growing evidence indicates that glioma stem cells (GSCs) and hypoxia drive this resistance and recurrence.</div><div>This review examines distinct GSC subtypes: mesenchymal GSCs, the most aggressive and invasive; proneural GSCs, which are more radiosensitive but highly proliferative and contribute to recurrence; and slow-cycling GSCs, which, though less well understood, are of growing interest due to their activation and deactivation during radiotherapy or through as-yet-unknown mechanisms. Hypoxia, a hallmark of the glioblastoma microenvironment, maintains these stem cells in a dedifferentiated state. As a key regulator, hypoxia orchestrates radioresistance mechanisms and promotes stem-like cell persistence through processes such as epithelial-mesenchymal transition-like (EMT-like), proneural-mesenchymal transition (PMT), or the reprogramming of differentiated cancer cells into GSCs.</div><div>The review concludes by highlighting therapeutic strategies under development to overcome radioresistance, including targeting GSCs, hypoxia, or employing alternative irradiation modalities beyond X-ray radiotherapy.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"149 ","pages":"Article 103198"},"PeriodicalIF":10.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148841670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting HER2 in urothelial carcinoma: from pathway inhibition to antibody–drug conjugates","authors":"Hamed Wafa,&nbsp;Nils C.H. van Creij,&nbsp;Michael Guenther,&nbsp;Maxim Noeparast,&nbsp;Jose Daniel Subiela,&nbsp;Angelika Terbuch,&nbsp;Dora Niedersuess-Beke,&nbsp;Zoran Culig,&nbsp;Steffen Ormanns,&nbsp;Renate Pichler","doi":"10.1016/j.ctrv.2026.103173","DOIUrl":"10.1016/j.ctrv.2026.103173","url":null,"abstract":"<div><div>Urothelial carcinoma (UC) is a biologically and clinically heterogeneous malignancy with persistently poor outcomes in locally advanced or metastatic disease. Although platinum-based chemotherapy and immune checkpoint inhibitors have improved survival, durable disease control remains limited, and therapeutic resistance is common. Antibody–drug conjugates (ADCs) targeting Nectin-4 and Trop-2 have further expanded the therapeutic landscape, yet the need for additional biomarker-driven strategies remains pressing. Human epidermal growth factor receptor 2 (HER2), encoded by <em>ERBB2</em>, has emerged as a therapeutically relevant target in a subset of UC. HER2 expression in UC is highly heterogeneous and varies across histological and molecular subtypes, with the highest expression rates reported in the micropapillary subtype. Early attempts to target HER2 in UC yielded disappointing results, largely due to biological heterogeneity, lack of standardized HER2 assessment and an incomplete understanding of HER2 pathway dependence in UC. Recent advances in molecular profiling and the development of HER2-directed ADCs have fundamentally reshaped the therapeutic relevance of HER2 in UC, enabling activity even in tumors with heterogeneous or low expression of HER2. This comprehensive narrative review synthesizes current knowledge on HER2 biology in UC, addresses challenges in biomarker assessment, critically appraises the evolving clinical trial landscape of HER2-directed ADCs, explores the interaction between HER2 and other oncogenic alterations and discusses mechanisms of resistance with future directions for HER2-targeted strategies in UC.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"148 ","pages":"Article 103173"},"PeriodicalIF":10.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148321270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early onset pancreatic Cancer: epidemiology, molecular features, and clinical outcomes","authors":"Fausto Petrelli,&nbsp;Lorenzo Dottorini,&nbsp;Andrea Celotti,&nbsp;Fausto Meriggi,&nbsp;Sara Cherri,&nbsp;Ester Oneda,&nbsp;Gianluca Tomasello,&nbsp;Michele Ghidini,&nbsp;Gianluca Baiocchi,&nbsp;Alberto Zaniboni","doi":"10.1016/j.ctrv.2026.103170","DOIUrl":"10.1016/j.ctrv.2026.103170","url":null,"abstract":"<div><div><strong>Background</strong> Early onset pancreatic cancer (EOPC), defined for the primary analysis as pancreatic ductal adenocarcinoma (PDAC) diagnosed before the age of 50 years, is an increasingly recognised clinical and epidemiological entity. Because published studies use heterogeneous age thresholds, the present review prespecified &lt;50 years as the main definition and interpreted studies using other cutoffs in sensitivity or narrative analyses.</div><div><strong>Methods</strong> We systematically searched PubMed, EMBASE, and the Cochrane Library for studies published between January 1990 and December 2024 that reported outcomes specific to EOPC. Search terms were reformatted with standard quotation marks and included “pancreatic cancer”, “pancreatic adenocarcinoma”, “pancreatic ductal adenocarcinoma”, “early onset”, “young onset”, “young adult”, “age &lt; 50”, “age less than 50”, and “premature”. Meta-analytic procedures and epidemiological interpretation were re-reviewed with statistical/epidemiological input.</div><div><strong>Results</strong> 40 studies encompassing more than 285,000 patients were included. Global incident EOPC cases increased from 24,480 (1990) to 42,254 (2021), representing a 72·6% rise. Age-standardised prevalence rate increased by 17·0% (1·65 per 100,000 in 2021). EOPC patients have a 3·08% per year increase in the youngest age group (20–29 years) over 2010–2021. Germline pathogenic variants were identified in 17·3% of EOPC patients (vs 6·4% in older cohorts; OR 2·41, 95% CI 1·87–3·11). EOPC patients were more likely to receive treatment (OR 2·95, 95% CI 2·54–3·43; I² = 13%) and showed modestly improved overall survival (pooled HR 0·89, 95% CI 0·80–0·99; I² = 16%) compared with average or late onset disease.</div><div><strong>Conclusions</strong> EOPC is an increasingly recognised and clinically challenging subset of PDAC. The substantial hereditary and potentially actionable molecular burden supports universal germline testing and comprehensive tumour genomic profiling, particularly in younger patients and in KRAS wild-type disease. PARP inhibitors should be described as improving progression-free survival or disease-control outcomes in selected BRCA-mutated metastatic PDAC rather than as having established a statistically significant overall survival benefit.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"148 ","pages":"Article 103170"},"PeriodicalIF":10.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148321292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment of breast cancer brain metastases in the era of novel drugs","authors":"Julian David Etessami,&nbsp;Giovanni Dalla Via,&nbsp;Emanuela Ferraro,&nbsp;Dario Trapani,&nbsp;Giuseppe Curigliano,&nbsp;Antonio Marra","doi":"10.1016/j.ctrv.2026.103179","DOIUrl":"10.1016/j.ctrv.2026.103179","url":null,"abstract":"<div><div>Brain metastases from breast cancer (BCBMs) are a major cause of morbidity and mortality and remain a critical unmet clinical need across molecular subtypes. Their incidence is rising as improved systemic therapies prolong survival in metastatic breast cancer and advances in neuroimaging allow earlier detection of central nervous system (CNS) disease. Historically, management relied mainly on local approaches such as surgery and radiotherapy because many systemic agents have limited ability to cross the blood–brain barrier. However, the therapeutic landscape is rapidly evolving with the development of systemic treatments showing clinically meaningful intracranial activity. In hormone receptor–positive/HER2-negative disease, treatment options are expanding with targeted and novel endocrine-based therapies that may achieve therapeutically relevant CNS concentrations. In addition, targeting the PI3K/AKT/mTOR pathway and the increasing use of antibody–drug conjugates (ADCs), including trastuzumab deruxtecan in HER2-low and-ultralow disease, may further broaden systemic strategies. In HER2-positive breast cancer, brain-penetrant tyrosine kinase inhibitors and highly active ADCs have significantly improved outcomes. Tucatinib-based combinations and trastuzumab deruxtecan have demonstrated substantial intracranial activity in prospective trials, shifting the treatment paradigm by supporting systemic therapy even in the presence of active brain metastases. Lastly, in triple-negative breast cancer, outcomes remain poor, but ADCs, immunotherapy-based strategies, and PARP inhibitors for germline BRCA-mutated disease are under investigation. A major limitation remains the underrepresentation of patients with brain metastases in clinical trials. This review summarizes current evidence on systemic therapies for BCBM across subtypes and highlights the need for CNS-inclusive trials and the development of effective CNS-active treatments.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"148 ","pages":"Article 103179"},"PeriodicalIF":10.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148355011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cyclotherapy: exploiting cell-cycle decoupling for selective cancer cytotoxicity and normal-tissue protection","authors":"D. Izzo,&nbsp;R.M. Marsicano,&nbsp;D. Trapani,&nbsp;G. Curigliano","doi":"10.1016/j.ctrv.2026.103172","DOIUrl":"10.1016/j.ctrv.2026.103172","url":null,"abstract":"<div><div>The therapeutic index of cytotoxic anticancer agents remains intrinsically constrained by the vulnerability of normal proliferating tissues. Unlike antibiotics, whose selectivity transformed infectious disease prognosis, most chemotherapeutics exert non-discriminatory effects on malignant and healthy cycling cells, resulting in dose-limiting toxicities that curtail clinical efficacy. Cyclotherapy represents a strategy first conceptualized in the early 2000s, that seeks to pharmacologically widen this therapeutic window by transiently arresting normal cells in specific phases of the cell cycle, thereby shielding them from phase-specific cytotoxic agents while leaving checkpoint-defective tumor cells susceptible. This review revisits the biological rationale, preclinical foundations, and clinical trajectory of cyclotherapy. Early approaches leveraging p53 activation and MDM2 inhibition demonstrated proof-of-principle but faced translational limitations. More recently, the development of short-acting CDK4/6 inhibitors, particularly trilaciclib, has provided the first clinically approved example of pharmacologic myeloprotection in small-cell lung cancer. However, inconsistent results across tumor types underscore the context-dependency of cyclotherapy, highlighting the critical importance of tumor-specific cell-cycle vulnerabilities, such as RB1 loss and precise pharmacologic scheduling. We propose a mechanistically informed framework for cyclotherapy development based on three determinants: tumor sensitivity to the protective agent, the cell-cycle dependency of treatment-related toxicities, and the phase specificity of the partnered targeted drug. Reframing adverse events according to cycle-dependent versus cycle-independent mechanisms may enable more rational therapeutic pairings and potentially support safe dose escalation. Cyclotherapy should not be regarded as a failed hypothesis prematurely tested, but as an evolving paradigm requiring refined biological stratification and temporal optimization. Properly implemented, it may redefine cytoprotection and expand the therapeutic latitude of modern oncology.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"148 ","pages":"Article 103172"},"PeriodicalIF":10.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148310788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond body surface area: CT-derived body composition as a predictor of chemotherapy toxicity and survival in pancreatic ductal adenocarcinoma: a systematic review","authors":"Beatriz Chacón-Ovejero,&nbsp;Vilma Pacheco-Barcia,&nbsp;Magda Palka-Kotlowska,&nbsp;Sara Custodio-Cabello,&nbsp;Raul Guerra-Hernandez,&nbsp;Paula Jimenez-Fonseca,&nbsp;Andrés Muñoz-Martin,&nbsp;Jorge Francisco Gómez-Cerezo,&nbsp;Luis Cabezón-Gutiérrez","doi":"10.1016/j.ctrv.2026.103174","DOIUrl":"10.1016/j.ctrv.2026.103174","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Pancreatic ductal adenocarcinoma (PDAC) is characterised by a high prevalence of severe muscle wasting (sarcopenia) and fatty muscle infiltration (myosteatosis), yet chemotherapy dosing still relies on body surface area (BSA), a metric that does not reflect individual patients' lean body mass (LBM) or muscle quality. A growing body of evidence from oncology meta-analyses demonstrates that low skeletal muscle mass (sarcopenia) independently predicts chemotherapy toxicity across multiple cancer types, and that myosteatosis is associated with significantly increased mortality risk. We performed a systematic review to determine whether CT-based body composition metrics better predict chemotherapy toxicity and survival outcomes in PDAC than conventional BSA-based dosing.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;We searched PubMed and EMBASE (up to 10 April 2026) according to PRISMA 2020 guidelines. Of 340 identified records, a total of 16 were included after screening and eligibility assessment: 14 primary studies/abstracts (10 retrospective cohorts, 1 prospective study, 3 conference abstracts); 2 prior systematic reviews were appraised qualitatively for contextual background. Methodological quality was assessed using the Newcastle–Ottawa Scale (NOS) for cohort studies and AMSTAR-2 for systematic reviews. Conference abstracts were assessed qualitatively; their inclusion and associated limitations are transparently acknowledged. Data were extracted on severe (grade ≥ 3) toxicities graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), dose-limiting toxicities (DLT), treatment modifications, and overall survival. Body composition measures assessed included skeletal muscle index (SMI) and skeletal muscle density (SMD) (surrogates for muscle quantity and quality, respectively), visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and longitudinal changes in these parameters.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Muscle quality (low SMD/myosteatosis) was as predictive of severe toxicity as muscle mass (SMI) in multiple studies, and when low SMI and SMD co-occurred, patients had significantly higher odds of grade ≥ 3 toxicity (odds ratio ∼ 1.7 in the largest cohort of 636 patients). Patients receiving high chemotherapy doses relative to LBM (e.g. &gt;5.8 mg of nab-paclitaxel per kg LBM) were significantly more likely to experience DLT (&lt;em&gt;p&lt;/em&gt; = 0.028), whereas standard BSA-normalised dosing did not discriminate risk. Early skeletal muscle loss (≥7.9% SMI decline within 2 months of FOLFIRINOX) was linked to a fourfold higher risk of mortality (HR 4.02; 95% CI 1.54–10.5). Overall, CT-derived body composition measures consistently outperformed BSA for toxicity and outcome prediction, although evidence remains largely retrospective and heterogeneous. Automated CT body composition analysis was demonstrated to be feasible, supporting integration into routine PDAC care.","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"148 ","pages":"Article 103174"},"PeriodicalIF":10.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148341509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Precision targeting of CLDN18.2: A new therapeutic paradigm for gastric cancer","authors":"Wei Zhou,&nbsp;Wuxuan Mei,&nbsp;Changchun Zeng","doi":"10.1016/j.ctrv.2026.103176","DOIUrl":"10.1016/j.ctrv.2026.103176","url":null,"abstract":"<div><div>Claudin 18.2 (CLDN18.2) is an attractive therapeutic target in gastric cancer (GC). Zolbetuximab, a CLDN18.2-targeted monoclonal antibody, has been approved in combination with chemotherapy as a first-line treatment option for patients with HER2-negative and CLDN18.2-positive gastric adenocarcinoma. This review summarizes current advances in CLDN18.2-targeted therapies for GC, with a focus on the clinical development of monoclonal antibodies (mAbs), particularly zolbetuximab and emerging next-generation antibodies, as well as mAb-based combination strategies. This review also summarizes CLDN18.2-targeted antibody-drug conjugates (ADCs), bispecific antibodies (BsAbs), and chimeric antigen receptor (CAR)-T cell therapy, highlighting emerging therapeutic strategies. Furthermore, major challenges and considerations in clinical and translational research are outlined. In conclusion, precision targeting of CLDN18.2 represents a promising approach in GC therapy, shifting from conventional chemotherapy to biomarker-guided strategies. Continued development of next-generation agents and rational combination therapies may enhance outcomes and expand benefit.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"148 ","pages":"Article 103176"},"PeriodicalIF":10.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148341523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Standardization of objectives and response criteria for neoadjuvant immunotherapy in resectable squamous cell carcinoma of the head and neck","authors":"Carlo Resteghini,&nbsp;Athanassios Argiris,&nbsp;Pierre Blanchard,&nbsp;Irene Braña,&nbsp;Anna Maria Camarda,&nbsp;Anthony T.C. Chan,&nbsp;Robert Ferris,&nbsp;Vincent Gregoire,&nbsp;Kevin J. Harrington,&nbsp;Ingeborg Tinhofer,&nbsp;Senada Koljenović,&nbsp;Nancy Y. Lee,&nbsp;C. René Leemans,&nbsp;Jean-Pascal Machiels,&nbsp;Hisham Mehanna,&nbsp;Robert Metcalf,&nbsp;Brian O'Sullivan,&nbsp;Sjoukje Oosting,&nbsp;Ester Orlandi,&nbsp;Vinidh Paleri,&nbsp;Paolo Bossi","doi":"10.1016/j.ctrv.2026.103175","DOIUrl":"10.1016/j.ctrv.2026.103175","url":null,"abstract":"<div><div>The management of locally-advanced, resectable head and neck squamous cell carcinoma (HNSCC) is undergoing a major shift driven by the integration of neoadjuvant immunotherapy (nIO). The rationale for nIO lies in its administration within an immunologically active, treatment-naïve microenvironment that enhances immune priming and anti-tumor response. Despite encouraging clinical data, including the pivotal KEYNOTE-689 trial and multiple phase II studies, methodological heterogeneity in trial design, endpoint definitions, and response criteria currently hampers data comparability and the establishment of new standards of care. This expert narrative review proposes a structured framework for standardizing clinical, pathologic, imaging, and translational endpoints in HNSCC nIO trials, highlighting harmonized definitions of pathologic response, practical reporting templates, and methods to evaluate immune priming.</div><div>Standardization of response evaluation, biomarker integration, and trial methodology is essential to accelerate the translation of neoadjuvant immunotherapy into routine clinical practice for HNSCC.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"148 ","pages":"Article 103175"},"PeriodicalIF":10.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148347763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antiangiogenic therapies in gastric cancer: future directions for 2026 and beyond: an UNICANCER gastrointestinal group (UCGI) perspective","authors":"Judith Raimbourg,&nbsp;Meher Ben Abdelghani,&nbsp;Valerie Boige,&nbsp;Damien Botsen,&nbsp;Aurélien Carnot,&nbsp;Clélia Coutzac,&nbsp;Matthieu Delaye,&nbsp;Nicolas De Sousa Carvalho,&nbsp;Mélanie Dos Santos,&nbsp;Julien Edeline,&nbsp;François Ghiringhelli,&nbsp;Aurélien Lambert,&nbsp;Samuel Le Sourd,&nbsp;Lola-Jade Palmieri,&nbsp;Simon Pernot,&nbsp;Emmanuelle Samalin,&nbsp;Cristina Smolenschi,&nbsp;Justine Vivier-Chicoteau,&nbsp;Sébastien Marion,&nbsp;Christelle de la Fouchardière","doi":"10.1016/j.ctrv.2026.103177","DOIUrl":"10.1016/j.ctrv.2026.103177","url":null,"abstract":"<div><div>Antiangiogenic therapies have been extensively investigated in advanced/metastatic gastric cancers, but also in neoadjuvant settings. The anti-Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) monoclonal antibody ramucirumab was the first antiangiogenic agent approved for HER2-negative metastatic gastric adenocarcinomas and remains a standard second-line treatment either alone or in combination with paclitaxel. Other VEGFR-targeting agents, such as the tyrosine kinase inhibitors (TKI) regorafenib and apatinib, have failed to demonstrate any survival benefit in the first-line settings, while providing modest improvements in pretreated patients, even when combined with Immune Checkpoint Inhibitors (ICI). Despite showing no significant benefit in Caucasian patients, apatinib has been approved in China for pretreated patients with advanced/metastatic gastric cancer. Dose-limiting toxicities, and the lack of robust predictive biomarkers for patients' stratification may both contribute to the limited efficacy of these multi-target tyrosine kinase inhibitors in gastric cancers. Several ongoing clinical trials mostly conducted in China suggest that new generation of antiangiogenic agents, particularly bispecific antibodies targeting both VEGF and Programmed Cell Death 1 (PD-1) or its ligand PD-L1, may offer greater efficacy with reduced toxicity. However, these promising preliminary data await mature overall survival results as well as clinical validation in the global population. Developing more effective drugs is closely linked to identifying reliable predictive biomarkers, which are crucial for guiding patients' selection, monitoring treatment response and optimizing therapeutic combinations and sequencing. Although several biomarker candidates have been explored, reliable predictors are still awaited. This review summarizes current evidence and explores the future of antiangiogenic agents in gastric cancers.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"148 ","pages":"Article 103177"},"PeriodicalIF":10.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148371277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Re-challenge strategies in neuroendocrine tumours: adding another arrow in the quiver?","authors":"Lavinia Benini,&nbsp;Davide Ciardiello,&nbsp;Francesca Spada,&nbsp;Chiara Alessandra Cella,&nbsp;Lorenzo Gervaso,&nbsp;Cristiana Mulargiu,&nbsp;Maria Giulia Zampino,&nbsp;Nicola Fazio","doi":"10.1016/j.ctrv.2026.103171","DOIUrl":"10.1016/j.ctrv.2026.103171","url":null,"abstract":"<div><div>Retreatment strategies in neuroendocrine tumours have shown promising clinical activity, yet evidence to guide patient selection and optimal treatment modalities remains limited. In this narrative review, we summarise the currently available data on systemic retreatment approaches (<em>retreatment</em> and <em>reintroduction</em> strategies) and highlight biological and clinical key factors – such as the role of MGMT expression, tumour grade, and treatment-free interval – that may inform clinical decision-making. We also outline critical priorities for future clinical trial design, including the integration of predictive biomarkers and the development of standardized retreatment protocols. Further prospective, biomarker-driven studies are required not only to refine patient selection but also to establish whether rechallenge strategy may represent a biologically reasonable and clinically meaningful strategy.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"148 ","pages":"Article 103171"},"PeriodicalIF":10.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148280446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}