Cancer treatment reviews最新文献

{"title":"Diagnostic utility of urinary cell-free DNA in non-urothelial cancer: a systematic review, meta-analysis, & network meta-analysis","authors":"Shugo Yajima,&nbsp;Kohei Hirose,&nbsp;Hitoshi Masuda","doi":"10.1016/j.ctrv.2025.103047","DOIUrl":"10.1016/j.ctrv.2025.103047","url":null,"abstract":"<div><h3>Purpose</h3><div>Urinary cell-free DNA (ucfDNA) offers a noninvasive approach for cancer detection, but its diagnostic utility in non-urothelial cancers remains unclear. We systematically evaluated the diagnostic and prognostic value of ucfDNA for these cancers and compared its performance with other liquid biopsies through network <em>meta</em>-analysis.</div></div><div><h3>Experimental design</h3><div>We conducted a systematic search of PubMed, Cochrane Library, and other databases for studies from 2010 to 2025 evaluating ucfDNA for diagnosing or predicting prognosis in non-urothelial cancers. Primary outcomes were pooled diagnostic sensitivity and specificity; secondary outcomes included prognostic hazard ratios (HRs). Study quality was assessed using QUADAS-2, and Bayesian hierarchical models were employed for robust estimates.</div></div><div><h3>Results</h3><div>Twenty-eight studies involving 4,423 participants were included. Overall pooled sensitivity was 0.80 (95 % CI, 0.75–0.85) and specificity was 0.96 (95 % CI, 0.88–0.98), with significant heterogeneity (<em>I</em>² &gt; 82 %). Subgroup analysis of studies targeting short amplicons (&lt;70 bp) showed improved specificity of 0.98 and substantially reduced heterogeneity (<em>I</em>² = 0 % for specificity). Limited post-treatment ucfDNA reduction was a strong predictor of poor prognosis (pooled HR, 2.76; 95 % CI, 1.94–3.91). Exploratory network <em>meta</em>-analysis in non-small cell lung cancer comparing urine, plasma, and sputum showed overlapping confidence intervals, though the limited available data and wide confidence intervals preclude definitive conclusions regarding comparative performance. Mutation-based assays demonstrated significantly higher specificity than methylation-based approaches (99 % vs. 72 %, <em>P</em> &lt; 0.01).</div></div><div><h3>Conclusions</h3><div>ucfDNA demonstrates high diagnostic specificity for non-urothelial cancers and provides significant prognostic information. Optimizing assays for ultrashort DNA fragments is critical for enhancing performance and reducing variability. These findings support the potential utility of ucfDNA, particularly as a complementary tool alongside established liquid biopsies like plasma cfDNA, to enhance non-invasive cancer diagnosis and monitoring. Its role as a standalone diagnostic requires further validation, and method standardization remains essential for broad implementation.</div></div><div><h3>Clinical trial registration</h3><div>PROSPERO CRD420251073863.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"141 ","pages":"Article 103047"},"PeriodicalIF":10.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145517242","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":"Evolving treatment strategies for resectable gastric cancer: Bridging Asia-West disparities toward personalized and integrated therapy","authors":"Xuesong Zhao ,&nbsp;Qianyun Hao ,&nbsp;Maria Alsina ,&nbsp;Daniel Acosta ,&nbsp;Florian Castet ,&nbsp;Eduardo Terán ,&nbsp;Kreina Vega Cano ,&nbsp;Tamara Saurí ,&nbsp;Ismael Macías ,&nbsp;Takaki Yoshikawa ,&nbsp;Sandra Castro ,&nbsp;Hirokazu Shoji ,&nbsp;Florian Lordick ,&nbsp;Zhanlong Shen ,&nbsp;Tian V. Tian ,&nbsp;Teresa Macarulla","doi":"10.1016/j.ctrv.2025.103041","DOIUrl":"10.1016/j.ctrv.2025.103041","url":null,"abstract":"<div><div>Gastric cancer (GC) remains a significant global health burden. Both Asian countries and Western nations, represented by Europe and North America, have long been pioneers in GC research and continue to lead advancements in the field. However, notable differences have historically existed between these regions in the treatment of resectable GC. In recent years, increasing convergence between Asian and Western approaches has emerged, driven by the growth of global collaborative studies. New definitive evidence suggests that the therapeutic landscape for resectable GC may undergo a significant transformation. In this review, we comprehensively examine the evolution of surgical approaches and perioperative chemotherapy strategies in Asia and the West. We summarize key clinical trials, highlight persistent survival disparities, and provide insight into current trends in perioperative management, including the recent advances in molecularly driven perioperative treatments. Finally, we outline key considerations for future multicenter perioperative trials to further guide global clinical practice.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"141 ","pages":"Article 103041"},"PeriodicalIF":10.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145446936","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":"Angiogenesis and thymic epithelial tumors: from preclinical insights to different therapeutic lines and combination strategies","authors":"D. Miliziano ,&nbsp;C. Sciortino ,&nbsp;S. Manglaviti ,&nbsp;M. Ganzinelli ,&nbsp;A. Lopez-Gutierrez ,&nbsp;M. Occhipinti ,&nbsp;C. Proto ,&nbsp;F. De Braud ,&nbsp;B. Besse ,&nbsp;G. Lo Russo ,&nbsp;J. Remon","doi":"10.1016/j.ctrv.2025.103049","DOIUrl":"10.1016/j.ctrv.2025.103049","url":null,"abstract":"<div><div>Thymic epithelial tumors (TETs) are rare thoracic malignancies for which surgical resection remains the mainstay treatment, even in advanced stages. For patients with metastatic disease, platinum-based chemotherapy represents the current standard of care in the first-line, with no standard treatment at progression. Much preclinical evidence supports a potential role of angiogenesis in the pathogenesis and progression of TETs. This biological rationale has led to assess the efficacy of several antiangiogenic agents, either in monotherapy or in combination in pre-treated metastatic TET, reporting a clinical meaningful outcome. Despite this efficacy several challenges remain such as the optimal place of angiogenic agents in the treatment sequence, whether they should be applied as monotherapy or in combination, as well as the potential clinical activity of sequential antiangiogenic agents with different mechanisms of action. In this review, we provide a comprehensive overview of the preclinical and clinical evidence supporting angiogenesis as a therapeutic target in TETs. We also propose potential treatment algorithms based on the current literature, while highlighting the ongoing challenges in defining optimal dosing strategies and treatment sequences in this rare disease.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"141 ","pages":"Article 103049"},"PeriodicalIF":10.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145558607","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":"Transformation from EGFR-mutant lung adenocarcinoma to small-cell lung cancer: from clonal evolution to lineage reprogramming","authors":"Haoxin Wang ,&nbsp;Nan Gao ,&nbsp;Lu Wang ,&nbsp;Feiran Yang ,&nbsp;Bin Liu ,&nbsp;Xiwen Hu ,&nbsp;Yufeng Zhao ,&nbsp;Rui Sha ,&nbsp;Xiurong Li ,&nbsp;Huijie Li","doi":"10.1016/j.ctrv.2025.103044","DOIUrl":"10.1016/j.ctrv.2025.103044","url":null,"abstract":"<div><div>EGFR-mutant lung adenocarcinoma (LUAD) that transforms into small-cell lung cancer (SCLC) following targeted therapy represents a clinically significant mechanism of acquired resistance, occurring in approximately 3–14 % of cases. This transformed variant, referred to as SCLC after transformation (SCLC-AT), follows an aggressive clinical course and carries a poor prognosis. SCLC-AT retains the original EGFR mutation but significantly down-regulates EGFR protein expression, eliminating its dependence on EGFR signaling while simultaneously acquiring a neuroendocrine phenotype. In nearly all cases, bi-allelic inactivation of both TP53 and RB1 is observed. In this overview, we provide a detailed examination of the molecular mechanisms underlying the transition from EGFR-mutant LUAD to SCLC. By integrating two primary biological concepts, clonal evolution and lineage reprogramming, we examine recent advances concerning the original cell or cells involved, as well as the genetic and epigenetic reprogramming and signaling pathway changes. While the transformation to SCLC is currently considered genetically and epigenetically irreversible, preclinical interventions targeting EZH2, AURKA, and DLL3 have shown potential in reversing the neuroendocrine phenotype or improving tumor immunogenicity. Future research should utilize single-cell and spatial multi-omics technologies to develop predictive models that can facilitate the early detection of impending transformation and guide precision therapies, ultimately enhancing patient outcomes.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"141 ","pages":"Article 103044"},"PeriodicalIF":10.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145463282","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":"CAR-T cell therapy in hepatocellular carcinoma: from mechanistic insights to clinical translation","authors":"Reza Elahi ,&nbsp;Yassine Alami Idrissi ,&nbsp;Anwaar Saeed","doi":"10.1016/j.ctrv.2025.103046","DOIUrl":"10.1016/j.ctrv.2025.103046","url":null,"abstract":"<div><div>Chimeric antigen receptor (CAR)-T cell therapy has transformed cancer immunotherapy, achieving durable complete remissions in hematologic cancers. Yet its translation to solid tumors like hepatocellular carcinoma (HCC), a leading cause of cancer-related deaths worldwide, faces formidable barriers, including immunosuppressive tumor microenvironments (TMEs), antigen heterogeneity, and risks of on-target/off-tumor toxicity. This review discusses the evolving role of CAR-T therapy in HCC across three domains: (1) foundational concepts in CAR-T design, mechanistic action, and antigen-targeting strategies; (2) breakthroughs from preclinical studies and early-phase clinical trials, such as glypican-3 (GPC3) and alpha-fetoprotein (AFP) directed CAR-T cells that have demonstrated preliminary safety and anti-tumor activity; and (3) innovative strategies to overcome TME-driven resistance, including metabolic reprogramming and stromal modulation. We highlight cutting-edge engineering solutions such as armored CAR-T cells engineered for cytokine support, dual-targeting constructs to mitigate antigen escape, and hypoxia-resistant designs alongside synergistic approaches combining CAR-T with immune checkpoint inhibitors or tyrosine kinase inhibitors. Furthermore, we dissect emerging tactics to disrupt TME immunosuppression. While CAR-T therapy holds promise for redefining HCC management, its success will depend on overcoming biological and logistical barriers through patient-tailored designs and robust translational pipelines. Future directions should prioritize biomarker-driven clinical trials, scalable manufacturing platforms, and integration with existing multimodal HCC therapies to maximize durable responses.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"141 ","pages":"Article 103046"},"PeriodicalIF":10.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145517307","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":"Expert consensus on the combination of Anti-EGFR monoclonal antibodies and immune checkpoint inhibitors in the treatment of head and neck squamous cell carcinoma","authors":"Liqiong Xue ,&nbsp;Tingting Xu ,&nbsp;Guochun Cao ,&nbsp;Xiaozhong Chen ,&nbsp;Meiyu Fang ,&nbsp;Mei Feng ,&nbsp;Lin Gui ,&nbsp;Fei Han ,&nbsp;Yaqian Han ,&nbsp;Chuncheng Hao ,&nbsp;Man Hu ,&nbsp;Wenxiao Huang ,&nbsp;Dongmei Ji ,&nbsp;Hao Jiang ,&nbsp;Shaojun Lin ,&nbsp;Lei Liu ,&nbsp;Zhigang Liu ,&nbsp;Haijun Lu ,&nbsp;Song Qu ,&nbsp;Guoxin Ren ,&nbsp;Chaosu Hu","doi":"10.1016/j.ctrv.2025.103048","DOIUrl":"10.1016/j.ctrv.2025.103048","url":null,"abstract":"<div><div>Head and neck squamous cell carcinoma (HNSCC) is the most prevalent type of head and neck cancer; however, treatment outcomes and patient prognosis remain suboptimal. Although the survival of patients with HNSCC has improved with the widespread use of anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs) and immune checkpoint inhibitors (ICIs), there remains considerable potential for further improvement. Recent studies suggest that the combination of anti-EGFR monoclonal antibodies and ICIs demonstrates promising efficacy and safety, which has been recommended by international guidelines for patients with recurrent or metastatic disease. Nevertheless, the application of this combination therapy remains in the early stages of exploration, and numerous questions concerning its standardized clinical use remain unanswered, including the mechanisms underlying the synergistic effects of individual agents, therapeutic value across different patient populations, and safety considerations. The Expert Committee of Head and Neck Cancer of the Chinese Society of Clinical Oncology (CSCO) organized an expert panel to develop this expert consensus on the combination of anti-EGFR mAbs and ICIs in the treatment of HNSCC through multiple rounds of discussion based on evidence-based medicine and clinical practice experience. This consensus provides guidance on the mechanisms of treatment with anti-EGFR mAbs plus ICIs, stratified treatment approaches, applications in special populations, and safety management. It is hoped that this consensus will provide clearer and more practical guidance for clinicians, promote the rational application of this combination therapy in clinical practice, and offer more treatment options for patients with HNSCC.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"141 ","pages":"Article 103048"},"PeriodicalIF":10.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145552052","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":"An umbrella review of systematic reviews on the diagnostic and prognostic utility of circulating tumor DNA and MicroRNA in colorectal cancer","authors":"Sameh Hany Emile ,&nbsp;Anjelli Wignakumar ,&nbsp;Ajia Syed ,&nbsp;Nir Horesh ,&nbsp;Samer Hani Barsom ,&nbsp;Zoe Garoufalia ,&nbsp;Steven D. Wexner","doi":"10.1016/j.ctrv.2025.103040","DOIUrl":"10.1016/j.ctrv.2025.103040","url":null,"abstract":"<div><h3>Background</h3><div>This umbrella review aimed to summarize and critically evaluate systematic reviews on the applications of circulating tumor DNA (ctDNA) and microRNA in colorectal cancer (CRC).</div></div><div><h3>Methods</h3><div>A PRISMA-compliant umbrella overview of systematic reviews was conducted. PubMed and Scopus were searched through October 2024 for systematic reviews that assessed the diagnostic and prognostic utility of ctDNA and microRNA in CRC. The diagnostic accuracy of ctDNA and microRNA in the detection of CRC and associated genetic mutations, and the association between ctDNA and disease recurrence and survival were assessed.</div></div><div><h3>Results</h3><div>26 systematic reviews were included. ctDNA had pooled sensitivity and specificity in detecting KRAS mutations of 75–83 % and 91–98 %, respectively. MicroRNA had a 59–76 % pooled sensitivity and 64–89 % pooled specificity in the detection of CRC. The detection of ctDNA after surgery for CRC was associated with increased recurrence, and the risk was higher when detection followed adjuvant chemotherapy. The detection of ctDNA was associated with an increased recurrence of colorectal metastases and worse overall survival. ctDNA was associated with an increased risk of rectal cancer recurrence and reduced odds of pathologic complete response when detected after neoadjuvant therapy and after surgery. The increased risk of recurrence associated with ctDNA was proportional to the disease stage; however, evidence on this observation is limited to one meta-analysis.</div></div><div><h3>Conclusions</h3><div>Detection of ctDNA before or after treatment of CRC, regardless of the stage, was associated with both increased recurrence and decreased survival. This negative impact was more notable when ctDNA was detected after locoregional treatment.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"141 ","pages":"Article 103040"},"PeriodicalIF":10.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145360443","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":"Corrigendum to “The importance of education and training in neuroendocrine neoplasms: challenges and opportunities for multidisciplinary management”. [Cancer Treat. Rev. 139 (2025) 102998]","authors":"Francesco Panzuto ,&nbsp;Simona Barbi ,&nbsp;Annalisa Trama ,&nbsp;Nicola Fazio","doi":"10.1016/j.ctrv.2025.103043","DOIUrl":"10.1016/j.ctrv.2025.103043","url":null,"abstract":"","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"141 ","pages":"Article 103043"},"PeriodicalIF":10.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145427241","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":"Clinical trials for older cancer patients: A systematic review","authors":"Roberta Fazio ,&nbsp;Alessandro Audisio ,&nbsp;Giacomo Bregni ,&nbsp;Daniel Sur ,&nbsp;Valentina Daprà ,&nbsp;Chiara Conti ,&nbsp;Fatima-Zahra Abbassi ,&nbsp;Nada Benhima ,&nbsp;Irene Assaf ,&nbsp;Lissandra Dal Lago ,&nbsp;Demetris Papamichael ,&nbsp;Jean-Luc Van Laethem ,&nbsp;Everardo D. Saad ,&nbsp;Francesco Sclafani","doi":"10.1016/j.ctrv.2025.103045","DOIUrl":"10.1016/j.ctrv.2025.103045","url":null,"abstract":"<div><div>Older adults are underrepresented in clinical trials, and studies specifically focused on older cancer patients are uncommon. By screening PubMed, EMBASE and proceedings from international meetings, we searched for trials testing systemic therapies in solid cancer patients aged ≥70 years. We identified age-unselected trials testing the same intervention in the same setting. The primary objective was to assess the proportion of older-age-selected trials meeting the target accrual. Secondary objectives included the analysis of the use of geriatric assessment (GA) tools and quality of life (QoL) questionnaires, and the comparison between older-age-selected and matching age-unselected trials.</div><div>We included 313 trials (10.9 % phase I, 78.6 % phase I/II-II, and 10.5 % phase III). 7.7 % were published in 1990–2000, 40.3 % in 2001–2011, and 52.1 % in 2012–2023. Of 234 evaluable trials, 77.8 % enrolled ≥90 % of the required patients. Premature study discontinuation occurred in 50 cases (5.9 % phase I, 14.2 % phase II, 39.4 % phase III). Among 232 evaluable trials, 60.3 % met the primary endpoint (63.7 % phase I/II-II, 35.5 % phase III). GA and QoL analyses were carried out in 28.1 % and 23 % of trials, respectively. Corresponding age-unselected trials were identified for 154 older-age-selected trials. Compared with age-unselected trials, a lower proportion of older-age-selected trials met the target accrual (83.5 % vs 94.8 %, p = 0.035) or the primary endpoint (63.9 % vs 81.5 %, p = 0.022). In conclusion, older-age-selected trials are increasingly performed but rarely include GA and QoL analyses. Effective strategies to meet target accrual should be implemented especially for phase III trials, which suffer from high rates of premature discontinuation.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"141 ","pages":"Article 103045"},"PeriodicalIF":10.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145497803","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 oncology in gastric cancer: Shaping the future of personalized treatment","authors":"Cristina Migliore ,&nbsp;Elisabetta Fenocchio ,&nbsp;Silvia Giordano ,&nbsp;Simona Corso","doi":"10.1016/j.ctrv.2025.103038","DOIUrl":"10.1016/j.ctrv.2025.103038","url":null,"abstract":"<div><div>Gastric cancer (GC) is the third leading cause of cancer-related mortality worldwide, and is associated with a very poor prognosis, largely due to its aggressive nature and, typically, late-stage diagnosis. Molecular classifications proposed one decade ago have provided valuable insights into the disease’s heterogeneity and paved the way for clinical trials of tailored treatments. However, most of these trials have failed, often due to inadequate patient selection, lack of reliable biomarkers of response/resistance, or for the high level of inter- and intra-tumor heterogeneity characterizing this disease.</div><div>This Review provides an in-depth and up-to-date overview of the preclinical models of GC developed in recent years. These include patient-derived xenografts (PDXs), organoids (PDOs), and genetically engineered mouse models (GEMMs), which are valuable tools for elucidating disease mechanisms and for preclinical drug testing. We also highlight emerging molecular targets and innovative therapeutic strategies—such as immunotherapies, antibody-drug conjugates, and synthetic lethality approaches—designed to overcome the mechanisms of resistance that limit current treatment efficacy.</div><div>Together, these improvements offer renewed hope for more effective and durable treatment options in GC, ultimately aiming to improve patient outcomes through a more tailored approach.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"141 ","pages":"Article 103038"},"PeriodicalIF":10.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145360769","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}