Cancer treatment reviews最新文献

{"title":"PD-(L)1 containing rechallenge strategies in patients with advanced NSCLC previously treated with immunotherapy: A systematic review and meta-analysis across resistance phenotypes","authors":"Daniele Marinelli ,&nbsp;Fabrizio Citarella ,&nbsp;Andrea Torchia ,&nbsp;Sagal Pannu ,&nbsp;Ayesha Aijaz ,&nbsp;Luisana Sisca ,&nbsp;Marco Russano ,&nbsp;Yu Fujiwara ,&nbsp;Kazuki Takada ,&nbsp;Amin H. Nassar ,&nbsp;Giuseppe Luigi Banna ,&nbsp;Biagio Ricciuti ,&nbsp;Leonardo Brunetti ,&nbsp;Valentina Santo ,&nbsp;Antonio Passaro ,&nbsp;Stephanie P.L. Saw ,&nbsp;Molly S.C. Li ,&nbsp;Alfredo Addeo ,&nbsp;Roberto Ferrara ,&nbsp;Massimo Di Maio ,&nbsp;Alessio Cortellini","doi":"10.1016/j.ctrv.2026.103159","DOIUrl":"10.1016/j.ctrv.2026.103159","url":null,"abstract":"<div><h3>Introduction</h3><div>Even though PD-(L)1 inhibitors have dramatically changed the prognosis of patients with advanced non-small-cell lung cancer (NSCLC), resistance to treatment remains common. Rechallenge with PD-(L)1 based regimens has been explored in this context, but clinical benefit remains uncertain.</div></div><div><h3>Methods</h3><div>Two independent reviewer teams performed parallel searches of MEDLINE and EMBASE from 2019 to 2025 to identify clinical trials evaluating PD-(L)1 inhibitor based rechallenge strategies in patients with advanced NSCLC previously treated with PD-(L)1-based regimens. Randomised controlled trials (RCTs) were included in quantitative <em>meta</em>-analysis, while non-randomised single-arm studies were synthesised descriptively. The primary endpoint was overall survival (OS). Sensitivity analyses examined outcomes according to resistance pattern. All analyses used fixed-effects models.</div></div><div><h3>Findings</h3><div>A total of 10 RCTs (n = 3,081) and 106 non-randomised interventional trials were included. Across RCTs, PD-(L)1 based rechallenge strategies yielded modest improvements in both OS (HR 0.91, 95%CI: 0.82–0.99) and PFS (HR 0.89, 95%CI: 0.81–0.99) compared with the control arms, with no improvement in objective response rate (ORR). In sensitivity analyses, no benefit was observed in patients with primary resistance, whereas those with acquired resistance features (i.e., clinical benefit to prior immunotherapy) demonstrated a more favourable effect for OS (HR 0.86, 95%CI: 0.77–0.97). A more restrictive analysis excluding patients with &lt; 3 months of prior PD-(L)1 exposure confirmed this pattern. Across the 106 single-arm trials, ORR varied widely, with only speculative signals of higher activity in regimens incorporating VEGF-targeting or chemotherapy.</div></div><div><h3>Conclusions</h3><div>In the largest synthesis of rechallenge strategies to date, PD-(L)1 rechallenge produced statistically significant but clinically marginal improvements in OS and PFS compared with standard treatments, with no benefit in patients with primary resistance. A signal of benefit was observed in patients with acquired resistance to prior immunotherapy although this exploratory analysis was limited by heterogeneous resistance definitions across trials and a non-significant interaction test.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"147 ","pages":"Article 103159"},"PeriodicalIF":10.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148145544","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":"The role of the 21-gene assay in the neoadjuvant setting for hormone receptor-positive HER2-negative breast cancer: Impact on systemic and surgical treatment decisions","authors":"Á.Guerrero Zotano ,&nbsp;T.M. Allweis ,&nbsp;R. Foerster ,&nbsp;C. Palmieri ,&nbsp;O. Gluz ,&nbsp;S. Chia ,&nbsp;C. Sotiriou ,&nbsp;G. Bianchini","doi":"10.1016/j.ctrv.2026.103161","DOIUrl":"10.1016/j.ctrv.2026.103161","url":null,"abstract":"<div><div>In breast cancer, one of the main objectives of neoadjuvant treatment, regardless of the specific breast cancer subtype, is to downstage the disease in both the breast and the lymph nodes, thereby allowing surgical de-escalation. In patients with inoperable disease, downstaging could lead to a feasible surgical resection; whereas, in patients presenting with operable disease, it could increase the eligibility for breast-conserving surgery (i.e., lumpectomy) instead of a mastectomy as well as spare some patients an axillary lymph node dissection. In patients with hormone receptor-positive (HR + ) human epidermal growth factor receptor 2 (HER2)-negative early-stage breast cancer, neoadjuvant treatment modalities include chemotherapy (NCT) and endocrine therapy (NET). The 21-gene Oncotype DX Breast Recurrence Score® assay is a multigene assay that determines a Recurrence Score® (RS) result (range, 0–100) based on gene expression profile within the primary tumor. The RS is a validated prognosticator and predictor of benefit from adjuvant CT. Beyond its validation, it has shown clinical utility in 3 prospective randomized clinical trials in the adjuvant setting (TAILORx, RxPONDER, and WSG PlanB). In these studies, all assays were performed on surgical excision samples. This review focuses on the utility of the 21-gene assay in patients with HR + HER2-negative early-stage breast cancer in the neoadjuvant setting. It discusses the analytical validation of performing the assay on core biopsies, its clinical validation as a tool to guide neoadjuvant treatment decisions (primary surgery, NET, or NCT), the association of the RS result with clinical outcomes, the impact of the RS results on neoadjuvant treatment decisions in real-life clinical practice, the inclusion of the assay in the neoadjuvant setting in clinical-practice guidelines, access of patients worldwide to this approach, and potential directions for additional studies examining the role of the RS in other steps in the clinical pathway of HR + HER2-negative early-stage breast cancer.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"147 ","pages":"Article 103161"},"PeriodicalIF":10.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148140185","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":"Treatments for human epidermal growth factor receptor 2 (HER2)–altered cancers evaluated using a tumor‑agnostic approach: A narrative review","authors":"Guilherme Harada ,&nbsp;Jamie E. Chaft ,&nbsp;Alison M. Schram ,&nbsp;Nick Pavlakis ,&nbsp;Yi-Long Wu","doi":"10.1016/j.ctrv.2026.103137","DOIUrl":"10.1016/j.ctrv.2026.103137","url":null,"abstract":"<div><div>Human epidermal growth factor receptor 2 (HER2) is a critical driver of tumorigenesis across a wide range of cancers, positioning it as a key target for tumor-agnostic therapies. Advances in HER2 therapies have shifted the treatment paradigm from histology-driven toward biomarker-driven, pan-tumor approaches. This review discusses the outcomes of approved and emerging HER2 therapies, highlighting the variability in efficacy across tumor types due to a combination of factors, such as HER2 heterogeneity, co-alterations, and tumor-specific resistance mechanisms. Although tumor-agnostic basket trials offer opportunities to evaluate HER2 therapies efficiently across multiple cancer types, challenges such as small patient populations, non-randomized designs, and heterogeneous tumor types can limit the reliability of their findings. Here, we review the available data on HER2 therapies in tumor-agnostic studies, with the goal of informing future clinical research and promoting greater appreciation of the nuances of HER2-altered cancers.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"147 ","pages":"Article 103137"},"PeriodicalIF":10.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148151318","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":"Prognostic role of postoperative circulating tumor DNA in metastatic colorectal cancer treated with curative intent: A systematic review and meta-analysis","authors":"Claudia Cardone ,&nbsp;Sergio Facchini ,&nbsp;Bruna de Oliveira Ascef ,&nbsp;Antonino Cassata ,&nbsp;Alfonso De Stefano ,&nbsp;Paolo Chiodini ,&nbsp;Antonio Avallone","doi":"10.1016/j.ctrv.2026.103160","DOIUrl":"10.1016/j.ctrv.2026.103160","url":null,"abstract":"<div><h3>Background</h3><div>Postoperative circulating tumor DNA (ctDNA) is an emerging biomarker for molecular residual disease (MRD) detection in early-stage colorectal cancer (CRC). However, its prognostic value in patients with resected metastatic disease has not been comprehensively assessed. This study aimed to evaluate the association between postoperative ctDNA detection and survival outcomes, including after completion of adjuvant chemotherapy (post-ACT), in patients with metastatic CRC (mCRC) treated with curative intent.</div></div><div><h3>Methods</h3><div>A systematic search of PubMed/MEDLINE, Scopus, and Embase was conducted up to March 17, 2025. Eligible studies included adults with mCRC undergoing curative intent treatment, reporting hazard ratios (HRs) for time-to-event outcomes according to postoperative ctDNA status. Random-effects <em>meta</em>-analyses were performed to pool HRs for recurrence-free survival (RFS) and overall survival (OS). Risk of bias was assessed using the QUIPS tool. The study followed PRISMA guidelines and was registered in PROSPERO (CRD42024528320).</div></div><div><h3>Results</h3><div>Sixteen studies (N = 1048) were included. Postoperative ctDNA positivity was detected in 409 patients (39.0%) and was associated with significantly worse RFS (16 studies; HR = 4.45, 95% CI, 3.44–5.75; P &lt; 0.0001) and shorter OS (9 studies; HR = 6.23; 95% CI, 3.15–12.33, P = 0.0003). Notably, post-ACT ctDNA positivity (N = 96, 41.4%) remained associated with recurrence (5 studies; HR, 6.08; 95% CI, 4.04–9.16; P &lt; 0.001).</div></div><div><h3>Conclusions</h3><div>Postoperative ctDNA positivity in mCRC treated with curative intent is strongly associated with increased risk of recurrence and mortality. These findings support its role as a consistent prognostic biomarker and highlight the need for biomarker-guided clinical trials in this setting.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"147 ","pages":"Article 103160"},"PeriodicalIF":10.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148102394","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":"Management of infections in the outpatient care of patients with cancer","authors":"Michael Sandherr ,&nbsp;Georg Maschmeyer ,&nbsp;Christina Rieger","doi":"10.1016/j.ctrv.2026.103142","DOIUrl":"10.1016/j.ctrv.2026.103142","url":null,"abstract":"<div><div>Infections are a common complication in immunocompromised patients with haematological and oncological diseases, including in outpatient settings. They lead to distressing morbidity and can delay or jeopardize the implementation of effective antineoplastic therapy. Identifying risk groups for complicated infections may reduce morbidity and mortality. The prevention of bacterial and viral infections as well as Pneumocystis jirovecii pneumonia through drug prophylaxis and consistent vaccination are essential here. In many cases, precise clinical evaluation of patients with febrile neutropenia allows for outpatient empirical and pre-emptive oral antimicrobial therapy and avoids unnecessary hospital stays.</div><div>These recommendations are based on guidelines developed by the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO) for the prophylaxis, diagnosis, and treatment of these patients, which are available on the Onkopedia platform of the DGHO (<span><span>www.onkopedia.com</span><svg><path></path></svg></span>). The recommendations are backed-up by systematic literature reviews, uniform assessment of the strength of evidence, and a consensus-building process.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"146 ","pages":"Article 103142"},"PeriodicalIF":10.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147803545","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":"Revisiting patient preference in resectable and irradiable stage III NSCLC in the immunotherapy era","authors":"Putora PM ,&nbsp;Dingemans AC ,&nbsp;Novoa NM ,&nbsp;Peters S ,&nbsp;Opitz I ,&nbsp;De Ruysscher DR","doi":"10.1016/j.ctrv.2026.103126","DOIUrl":"10.1016/j.ctrv.2026.103126","url":null,"abstract":"<div><div>The optimal local treatment for resectable stage III non-small cell lung cancer (NSCLC) remains controversial, with both surgery and radiotherapy considered valid options depending on tumor characteristics, comorbidities, and institutional expertise. The introduction of immunotherapy has improved outcomes in surgery- as well as radiotherapy-based treatment approaches. Current ESMO and NCCN guidelines demonstrate both consensus and discrepancies in N2 NSCLC. When both surgery and radiotherapy are feasible, patient preference should be considered in decision-making, supported by multidisciplinary discussion and current evidence.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"146 ","pages":"Article 103126"},"PeriodicalIF":10.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147792113","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":"Streptozotocin revisited: Pharmacological determinants supporting new scheduling strategies in neuroendocrine tumours","authors":"Nicola Fazio ,&nbsp;Francesca Spada ,&nbsp;Lavinia Benini ,&nbsp;Cristiana Mulargiu ,&nbsp;Marzia Del Re ,&nbsp;Romano Danesi","doi":"10.1016/j.ctrv.2026.103140","DOIUrl":"10.1016/j.ctrv.2026.103140","url":null,"abstract":"<div><div>Streptozotocin (STZ) remains a potentially effective chemotherapeutic agent for pancreatic neuroendocrine tumours, more than five decades after its initial use. Despite its longstanding clinical application, STZ dosing regimens have traditionally been driven by empirical practice rather than by pharmacokinetic or pharmacodynamic rationale. Recent advances in understanding its molecular mechanism of action, selective uptake via the glucose transporter type 2 transporter, and DNA-methylating properties provide a solid foundation for revisiting its therapeutic role and optimising its scheduling.</div><div>This review outlines the key pharmacological features of STZ, including its rapid systemic clearance, narrow volume of distribution, and renal elimination, all of which support the use of short intravenous infusions and fractionated schedules to minimise nephrotoxicity while maintaining efficacy. Comparative insights with temozolomide highlight the unique delivery and tissue tropism advantages of STZ, particularly in pancreatic neuroendocrine tumours. In addition, emerging biomarkers, such as O⁶-methylguanine-DNA methyltransferase deficiency and mismatch repair status, may help refine patient selection for STZ-based chemotherapy.</div><div>Clinical data from classical and modern regimens, such as those combining STZ with 5-fluorouracil or capecitabine, suggest sustained disease control in well-selected patients. The potential for biomarker-guided strategies and pharmacology-informed protocols supports a contemporary repositioning of STZ in neuroendocrine oncology. Rational redesign of dosing, improved toxicity management, and integration with personalised medicine may revitalise the clinical utility of this historically valuable agent.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"146 ","pages":"Article 103140"},"PeriodicalIF":10.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147803544","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":"Expanding the therapeutic Frontier: Liver transplantation for unresectable colorectal liver metastases","authors":"Alex B. Munster ,&nbsp;Umair Mahmood ,&nbsp;Heather Fuller ,&nbsp;Hajun Seo ,&nbsp;Jamie Murphy ,&nbsp;Krishna Menon ,&nbsp;Charles Imber ,&nbsp;Chetan Bhan ,&nbsp;Khurum Khan","doi":"10.1016/j.ctrv.2026.103139","DOIUrl":"10.1016/j.ctrv.2026.103139","url":null,"abstract":"<div><div>A substantial proportion of patients with colorectal cancer present with or ultimately develop metastatic disease confined to the liver. The management of colorectal liver metastases remains one of the most complex and debated areas in oncological practice, with curative resection feasible in only a minority of cases. However, emerging evidence, most notably from the TransMet study, has reshaped the therapeutic landscape. The demonstration of a clear survival advantage in carefully selected patients with unresectable hepatic disease undergoing liver transplantation represents a transformative advance and challenges longstanding treatment paradigms. This narrative review critically appraises the epidemiological burden of colorectal liver metastases and delineates the key biological and clinical determinants underpinning their development. We synthesise the pivotal clinical trial data establishing the rationale for liver transplantation in this population and define the parameters for appropriate patient selection. The evolving perioperative integration of systemic therapies and the optimisation of postoperative surveillance strategies are examined in detail. Finally, we evaluate the emerging role of liquid biopsy as a precision tool to refine risk stratification and guide management, while addressing the ethical, logistical, and immunological considerations inherent to expanding transplant indications in this setting.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"146 ","pages":"Article 103139"},"PeriodicalIF":10.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147792101","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":"Hematological immune-related adverse events associated with checkpoint inhibitors","authors":"Mélanie Janson ,&nbsp;François Cherifi ,&nbsp;Hippolyte Bardet ,&nbsp;Gandhi Damaj","doi":"10.1016/j.ctrv.2026.103121","DOIUrl":"10.1016/j.ctrv.2026.103121","url":null,"abstract":"<div><h3>Background</h3><div>The use of immune checkpoint inhibitors (ICIs) has expanded substantially across tumor types, establishing them as a cornerstone of modern oncology. However, the frequency and severity of immune-related adverse events (irAEs) remain underestimated, particularly hematologic toxicities, which can be life-threatening and require distinct management approaches compared to cytotoxic or targeted therapies.</div></div><div><h3>Methods</h3><div>We performed literature reviews using PubMed to identify and analyze reported cases of the most frequent hematologic irAEs; autoimmune hemolytic anemia (AIHA), immune thrombocytopenia (ITP), and pure red cell aplasia (PRCA), in patients with solid tumors. In parallel, we report three illustrative cases from our institution to highlight diagnostic pitfalls and management strategies.</div></div><div><h3>Results</h3><div>The median onset of hematologic irAEs occurs after approximately 3 cycles of ICI therapy for AIHA and ITP, and after 4 cycles for PRCA. Most patients achieved remission with corticosteroid therapy; however, 10–15% were steroid-refractory or relapsed, requiring second-line immunosuppressive agents. Rechallenge with ICIs remains controversial due to a recurrence rate of irAE, although it may be feasible and clinically beneficial in carefully selected patients.</div></div><div><h3>Conclusion</h3><div>As the use of ICIs continues to rise, prompt recognition and management of hematologic irAEs are critical to minimize morbidity and to avoid premature discontinuation of immunotherapy. Increased clinician awareness and standardized diagnostic algorithms are essential to preserve both safety and efficacy.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"145 ","pages":"Article 103121"},"PeriodicalIF":10.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147577059","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":"Biomarker-guided immunotherapy in gastric cancer: current insights and future perspectives","authors":"Mar Teixidó Mulet ,&nbsp;Joel Veas Rodriguez ,&nbsp;Eduardo Terán ,&nbsp;Miquel Piñol ,&nbsp;Felip Vilardell ,&nbsp;Mar Iglesias ,&nbsp;Cinta Hierro ,&nbsp;Mariona Calvo ,&nbsp;Xavier Matias-Guiu ,&nbsp;Antonieta Salud ,&nbsp;Josep Tabernero ,&nbsp;Robert Montal","doi":"10.1016/j.ctrv.2026.103124","DOIUrl":"10.1016/j.ctrv.2026.103124","url":null,"abstract":"<div><div>Gastric and gastroesophageal junction adenocarcinoma (GC) is a biologically challenging malignancy associated with suboptimal clinical outcomes due to limited effective treatment options. The recent incorporation of immune checkpoint inhibitors (ICIs) into therapeutic algorithms has improved the clinical prospects of subsets of GC patients. However, responses to anti-PD-1/PD-L1 agents remain highly heterogeneous, with only some patients deriving long-term benefits. This variability highlights the importance of identifying optimal biomarkers to enhance patient selection, thereby enabling tailored immunotherapy strategies. Whereas microsatellite instability has demonstrated a potent capacity for predicting immunotherapy benefits in GC, other predictive biomarkers, such as PD-L1 expression, remain suboptimal. Advances in gene expression and epigenetic profiling, liquid biopsy approaches, gut microbiome characterization, and artificial intelligence-driven multimodal algorithms applied to multi-omics or digital pathology are key drivers for the comprehensive characterization of the GC tumour microenvironment (TME), which could be used for better treatment selection. Similarly, elucidating the complex tumour-immune interplay with these technologies will be crucial for the success of novel immunotherapeutic approaches under clinical development, by evaluating alternative immune pathways alone or in combination with current actionable targets of GC. The current review aims to give an overview of the current immunotherapeutic landscape in GC, evaluate standard-of-care and emerging biomarkers of immunotherapy response, and discuss the translational potential of incorporating multi-omic and AI-derived biomarkers into biomarker-enriched clinical decision-making frameworks.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"145 ","pages":"Article 103124"},"PeriodicalIF":10.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147596869","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}