Critical reviews in oncology/hematology最新文献

{"title":"Emerging Role of AI in Single-Cell Sequencing Toward Biomarker Discovery, Therapeutic Target Identification and Precision Medicine in Lung Cancer.","authors":"P K Fasna, Reshma Krishnan, Ravindra Kumar","doi":"10.1016/j.critrevonc.2026.105653","DOIUrl":"https://doi.org/10.1016/j.critrevonc.2026.105653","url":null,"abstract":"<p><p>Lung cancer, the most common malignancy worldwide, exists in numerous histological subtypes, rendering the diagnosis and prognosis of the disease a challenge to clinicians. The recent technological breakthroughs in single-cell sequencing (SCS) and Artificial Intelligence (AI) have expanded the existing knowledge of lung cancer biology and provided new opportunities in the area of precision medicine. SCS has the potential to expose the enormous complexity of tumors, showing heterogeneous cell populations and characterizing the tumor microenvironment, and thereby overcoming the inherent limitations of conventional bulk sequencing in resolving tumor heterogeneity. At the same time, AI's advanced machine learning (ML) and predictive modeling capabilities, when applied to SCS data, can facilitate the identification of subtle cellular states, dynamic cellular interactions, and complex molecular pathways often undetectable by traditional statistical methods. This review examines the emerging applications of SCS and AI in lung cancer, focusing on biomarker discovery, therapeutic target identification, and precision medicine. We outline how their integration may support the identification of new biomarkers and therapeutic targets, with implications for more personalized treatment approaches. Integration of single-cell biology knowledge with AI-based analytics may assist scientists and clinicians in addressing the shortcomings of traditional approaches, which may offer personalized therapies with the potential to improve patient care. The ultimate goal of this review is to address the challenges and future perspectives of this emerging trend by focusing on the potential of these technologies to fulfill the unmet needs in lung cancer diagnosis, prognosis, and treatment selection.</p>","PeriodicalId":93958,"journal":{"name":"Critical reviews in oncology/hematology","volume":" ","pages":"105653"},"PeriodicalIF":5.6,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149225302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic value of circulating tumor DNA in esophageal and gastric cancer by treatment stage: a systematic review and meta-analysis.","authors":"Shaoqing Ding, Minyuan Ni, Zeqi Tang, Shiyan Zhang, Xinhe Li, Zheyu Zhong, Chaoyue Ma, Xia Ye, Bangsheng Chen","doi":"10.1016/j.critrevonc.2026.105652","DOIUrl":"https://doi.org/10.1016/j.critrevonc.2026.105652","url":null,"abstract":"<p><strong>Background: </strong>The prognostic value of circulating tumor DNA (ctDNA) remains controversial. This meta-analysis systematically evaluates the association between ctDNA status and prognosis in esophageal cancer (EC) and gastric cancer (GC) (including gastroesophageal junction cancer), stratified by resectability and treatment stage.</p><p><strong>Methods: </strong>PubMed, Web of Science, EMBASE and Scopus were systematically searched up to February 2026. Pooled hazard ratios (HRs) and 95% confidence intervals (95%CIs) were used to quantify disease-free survival (DFS), progression-free survival (PFS), and overall survival (OS).</p><p><strong>Results: </strong>Forty-four studies were included: 28 on resectable cancer, 17 on unresectable cancer (among which one study covered both types). In resectable cancer, ctDNA positivity was associated with worse DFS at baseline (HR=2.45, 95%CI: 1.18-5.07), after neoadjuvant therapy (HR=3.89, 95%CI: 2.50-6.06), after radical surgery (HR=6.76, 95%CI: 4.72-9.67), and follow-up (HR=19.17, 95%CI: 12.69-28.96). ctDNA positivity was also associated with worse OS at baseline (HR=1.89, 95%CI: 1.13-3.16), after neoadjuvant therapy (HR=3.40, 95%CI: 2.03-5.69), and after radical surgery (HR=4.52, 95%CI: 2.70-7.58). In resectable cancer, ctDNA positivity was associated with both DFS and OS, and the association differed between treatment time points (DFS: Q-test P<0.001; OS: Q-test P=0.05). In unresectable cancer, baseline ctDNA positivity was associated with worse PFS (HR=2.17, 95%CI: 1.31-3.60) and OS (HR=2.04, 95%CI: 1.54-2.70). During treatment, ctDNA positivity was associated with worse PFS (HR=2.72, 95%CI: 1.63-4.52) and OS (HR=2.63, 95%CI: 1.52-4.55).</p><p><strong>Conclusion: </strong>ctDNA positivity was associated with worse prognosis in both resectable and unresectable EC and GC. In resectable cancer, the association with DFS and OS differed between treatment time points.</p>","PeriodicalId":93958,"journal":{"name":"Critical reviews in oncology/hematology","volume":" ","pages":"105652"},"PeriodicalIF":5.6,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149217495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiovascular Toxicities Associated With Immune Checkpoint Inhibitors: Clinical Phenotypes, Mechanisms, Diagnosis, and Management-A Narrative Review.","authors":"Shuhong Wu, Jieyi Yang, Xiaoman Wang, Jilu Lang, Wei-Jan Wang, Xian Sun","doi":"10.1016/j.critrevonc.2026.105646","DOIUrl":"https://doi.org/10.1016/j.critrevonc.2026.105646","url":null,"abstract":"<p><strong>Objective: </strong>Immune checkpoint inhibitors (ICIs) have improved cancer outcomes, yet cardiovascular toxicities remain difficult to recognize and manage. We review their clinical spectrum, mechanistic evidence, diagnostic work-up, surveillance, and treatment, with particular attention to where evidence is established and where it remains preliminary.</p><p><strong>Methods: </strong>We conducted a narrative review of PubMed through September 2026 and hand-searched reference lists of relevant guidelines, reviews, and primary studies. We prioritized international guidance, systematic reviews, multicenter registries, prospective cohorts, and clinically informative mechanistic studies. Case reports and experimental studies were retained when they addressed questions not covered by higher-level evidence. The review was not protocol driven and did not include duplicate screening, formal risk-of-bias assessment, or a PRISMA flow diagram.</p><p><strong>Results: </strong>ICI-related cardiovascular toxicity extends beyond myocarditis to temporally associated atherosclerotic events, pericardial disease, and heart failure without demonstrable myocardial inflammation, although causal attribution is less secure for these non-myocarditis phenotypes. Current guidance supports baseline cardiovascular assessment and risk-adapted surveillance, but neither a universal troponin threshold nor an outcome-proven monitoring schedule has been established. Corticosteroids remain first-line treatment for clinically significant ICI myocarditis. Abatacept, ruxolitinib, alemtuzumab, and other intensified regimens are off-label and rest largely on nonrandomized or case-level evidence.</p><p><strong>Conclusion: </strong>Management should combine early recognition, careful exclusion of competing diagnoses, and coordinated oncology-cardiology decision-making. Current evidence does not justify uniform screening thresholds or a standard rescue regimen, and investigational biomarkers, imaging probes, and targeted immunomodulators require prospective validation.</p>","PeriodicalId":93958,"journal":{"name":"Critical reviews in oncology/hematology","volume":" ","pages":"105646"},"PeriodicalIF":5.6,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149208376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Survival by Design: Cell Fate Dynamics in Classical Hodgkin Lymphoma.","authors":"Matei Seleusan, Diana Cenariu, Diana Gulei, David Kegyes, Adrian Bogdan Tigu, Sadia Riaz, Mihnea Zdrenghea, Ciprian Tomuleasa","doi":"10.1016/j.critrevonc.2026.105651","DOIUrl":"https://doi.org/10.1016/j.critrevonc.2026.105651","url":null,"abstract":"<p><p>Classical Hodgkin lymphoma (cHL) is singular because rare Hodgkin and Reed-Sternberg (HRS) cells survive within an abundant inflammatory tumor microenvironment (TME) - despite originating from germinal center (GC) B cells that would normally be negatively selected, they persist through coordinated disruption of lineage fidelity, immune recognition, and cell-death execution. The present review integrates mechanistic, translational, and therapeutic evidence on apoptosis resistance, survival signaling, microenvironmental support, immune evasion, Epstein-Barr virus-associated rescue mechanisms, and senescence-like phenotypes in cHL, with particular emphasis on how these processes converge to stabilize an aberrant HRS-cell fate by raising the apoptotic threshold. HRS cells retain several elements of apoptotic competence, including death receptors, functional mitochondrial apoptotic machinery, and frequently wild-type TP53; however, these factors are functionally restrained by multiple antagonistic mechanisms: c-FLIP inhibits pro-caspase-8 activation, constitutive NF-κB, JAK/STAT and PI3K/AKT signaling sustain survival, BCL-2-superfamily overexpression confers resistance to intrinsic apoptotic stimuli, MDM2 overactivity suppresses p53, and microenvironment-derived secretory products and contact-dependent ligands provide stabilizing support. The inflammatory niche reinforces HRS-cell persistence by converting immune proximity into immune privilege through altered antigen presentation, PD-1/PD-L1 signaling, spatially inhibitory rosetting structures, regulatory T-cell prevalence, M2-macrophage polarization, and cytokine-mediated paracrine and autocrine survival circuits. Emerging evidence indicates that Reed-Sternberg cells (RS) acquire senescence-like features and secretory programs that contribute to constructing the inflammatory niche. cHL can therefore be understood as a malignancy of failed fate execution, in which apoptosis, differentiation and immune clearance remain available but are rendered non-executable by convergent intrinsic and microenvironmental survival circuits.</p>","PeriodicalId":93958,"journal":{"name":"Critical reviews in oncology/hematology","volume":" ","pages":"105651"},"PeriodicalIF":5.6,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149198484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rewiring the Tumor-Immune Ecosystem: Extracellular Vesicles in the Next Era of Cancer Immunotherapy.","authors":"Ahmed Reda Bahr, Youssef Basem, Abdelrahman Alaa, Maria Tamer, Amira Basem, Mariam Hossam El-Deen, Esraa M Halawa","doi":"10.1016/j.critrevonc.2026.105642","DOIUrl":"https://doi.org/10.1016/j.critrevonc.2026.105642","url":null,"abstract":"<p><p>Cancer immunotherapy has transformed oncology by enabling immune-mediated tumor elimination; however, durable responses remain limited, particularly in solid tumors due to antigen heterogeneity, immunosuppressive tumor microenvironment, and adaptive resistance mechanisms. To overcome these barriers, therapeutic paradigms are expanding from single-agent interventions toward programmable cellular and acellular platforms. This review examines recent advances in CAR-T, CAR-NK, and TCR-engineered cell therapies alongside key resistance mechanisms. In parallel, we evaluate the dual biological role of extracellular vesicles (EVs) as mediators of immune evasion and as engineered delivery tools. Rather than presenting multimodal integration as an inherently superior solution, we critically evaluate the trade-offs of combining engineered cells, EVs, checkpoint blockade, oncolytic viruses, and targeted agents, focusing on therapeutic synergy versus cumulative toxicity and biomanufacturing complexity. Collectively, we propose that future cancer immunotherapy will rely on multi-modal, adaptive, and systems-level engineering approaches capable of dynamically reshaping the tumor-immune ecosystem to achieve sustained tumor regression and durable overall survival.</p>","PeriodicalId":93958,"journal":{"name":"Critical reviews in oncology/hematology","volume":" ","pages":"105642"},"PeriodicalIF":5.6,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149168274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circular RNAs in Breast Cancer Immunometabolism: Mechanisms of Immune Regulation and Metabolic Reprogramming.","authors":"Hailiang Jing, Jianing Jian, Chen Xing, Hong Luo","doi":"10.1016/j.critrevonc.2026.105645","DOIUrl":"https://doi.org/10.1016/j.critrevonc.2026.105645","url":null,"abstract":"<p><p>Metabolic reprogramming and immune dysfunction are increasingly recognized as interconnected hallmarks of breast cancer progression, collectively shaping tumor evolution, immune evasion, and therapeutic response. Emerging evidence identifies circular RNAs (circRNAs), a highly stable class of endogenous non-coding RNAs generated through back-splicing, as pivotal regulators of the immunometabolic crosstalk within the breast cancer tumor microenvironment (TME). Through diverse mechanisms, including microRNA sequestration, interactions with RNA-binding proteins, and modulation of transcriptional and signaling networks, circRNAs coordinate metabolic pathways such as glycolysis, lipid metabolism, glutamine utilization, and mitochondrial function while simultaneously regulating immune cell differentiation, cytokine signaling, and immune checkpoint pathways. These coordinated metabolic and immunological alterations promote the establishment of an immunosuppressive TME characterized by the accumulation of regulatory T cells, myeloid-derived suppressor cells, tumor-associated M2 macrophages, and dysfunctional cytotoxic lymphocytes, thereby facilitating tumor progression, immune escape, and resistance to both conventional therapies and immunotherapy. In this narrative review, we provide a structured synthesis of current evidence on how circRNAs participate in the intersection of metabolic reprogramming and immune regulation in breast cancer. Particular emphasis is placed on mechanistically supported interactions linking circRNAs with glycolysis, mitochondrial metabolism, lipid and glutamine metabolism, immune-cell function, and immune-checkpoint regulation, while evidence derived from non-breast-cancer models is explicitly distinguished from breast-cancer-specific findings. Finally, we explore the emerging clinical applications of circRNAs as diagnostic and prognostic biomarkers and evaluate their potential as therapeutic targets for immunometabolic intervention, emphasizing their promise for improving immunotherapeutic efficacy and advancing precision medicine in breast cancer.</p>","PeriodicalId":93958,"journal":{"name":"Critical reviews in oncology/hematology","volume":" ","pages":"105645"},"PeriodicalIF":5.6,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149149839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to \"When is immunotherapy too much? The case of favorable-risk metastatic renal cell carcinoma.\" [Crit. Rev. Oncol. Hematol. 2026 May:221:105238.].","authors":"Sebastiano Buti, Betty Dalla Valle, Alessandro Acunzo, Pietro Tuttobene, Prisca Tamarozzi, Virginia Agnetti, Michele Maffezzoli","doi":"10.1016/j.critrevonc.2026.105632","DOIUrl":"https://doi.org/10.1016/j.critrevonc.2026.105632","url":null,"abstract":"","PeriodicalId":93958,"journal":{"name":"Critical reviews in oncology/hematology","volume":" ","pages":"105632"},"PeriodicalIF":5.6,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149139713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FGFR-Altered Urothelial Carcinoma in the EV-Pembrolizumab Era: Rationale and Emerging Data for Upfront Triplet Strategies.","authors":"Claudia Maria Ascione, Raffaella Congi, Stella Feliciello, Carmine Caso, Felice Crocetto, Ciro Imbimbo, Alberto Servetto, Fabrizio Di Costanzo, Roberto Bianco, Daniela Esposito, Luigi Formisano","doi":"10.1016/j.critrevonc.2026.105641","DOIUrl":"https://doi.org/10.1016/j.critrevonc.2026.105641","url":null,"abstract":"<p><p>Urothelial cancer (UC) is a common malignancy with a significant incidence worldwide, particularly in Europe and North America. Approximately 5% of patients have de novo metastatic disease at the time of initial diagnosis. The combination of Enfortumab vedotin and Pembrolizumab recently transformed the first-line treatment landscape, providing better clinical outcomes and greater tolerability compared to traditional cisplatin-based therapies. However, alterations in fibroblast growth factor receptor (FGFR) signaling may diminish the effectiveness of Immune Checkpoint Inhibitors (ICIs), underscoring the need for novel combination therapies. This review examines emerging evidence supporting combination strategies incorporating pan-FGFR tyrosine kinase inhibitors in FGFR-altered urothelial carcinoma, focusing on their potential integration with first-line doublet regimens. Ongoing and future clinical studies will be essential to define the clinical value of these combinations and to advance precision immunotherapy strategies guided by genomic alterations, to improve outcomes for patients with UC.</p>","PeriodicalId":93958,"journal":{"name":"Critical reviews in oncology/hematology","volume":" ","pages":"105641"},"PeriodicalIF":5.6,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149129598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond the Generic Tumor: Engineering Patient-Specific Immune Ecosystems for Cancer.","authors":"Samira Anvari, Jalal Naghinezhad, Reza Farokhi, Mahshid Akhavan Rahnama, Saghar Hoseinzadeh, Mohsen Nikbakht, Mohammad Ahmadvand","doi":"10.1016/j.critrevonc.2026.105611","DOIUrl":"https://doi.org/10.1016/j.critrevonc.2026.105611","url":null,"abstract":"<p><p>Cancer immunotherapy has transformed the treatment landscape of malignancies; however, durable clinical responses remain limited by interpatient heterogeneity, tumor evolution, antigen loss, and variability in immune recognition. Advances in genomic sequencing, neoantigen discovery, immunopeptidomics, mRNA-based therapeutics, and cellular engineering have expanded opportunities for developing individualized immunotherapeutic strategies based on patient-specific tumor and immune characteristics. This review examines the state of personalized cancer immunotherapy, with emphasis on individualized neoantigen-specific therapies (iNeST), neoantigen vaccines, mRNA-based antigen delivery platforms, engineered T-cell approaches, and computational methods for antigen prioritization and immune-response prediction. We summarize the biological rationale, preclinical and clinical evidence, and limitations of these approaches, while considering their translational potential and clinical feasibility. We examine the relationships among tumor mutational landscapes, neoantigen immunogenicity, antigen processing and presentation, HLA restriction, immune-cell engineering, and computational immunology. We further assess key barriers to clinical implementation, including limitations in neoantigen prediction and validation, intratumoral heterogeneity, antigen evolution and loss, manufacturing complexity, scalability, regulatory requirements, and the need for prospective clinical validation. Overall, current evidence supports personalized immunotherapy as a promising approach for improving the precision of cancer treatment, but its clinical application remains constrained by biological, technical, manufacturing, regulatory, and clinical challenges. Future progress will require more accurate and experimentally validated neoantigen identification, improved computational and immunologic modeling, robust manufacturing and quality-control processes, and prospective clinical studies demonstrating safety, feasibility, and therapeutic benefit. This review evaluates the current evidence, identifies knowledge gaps, and outlines priorities for the responsible clinical development of individualized cancer immunotherapy.</p>","PeriodicalId":93958,"journal":{"name":"Critical reviews in oncology/hematology","volume":" ","pages":"105611"},"PeriodicalIF":5.6,"publicationDate":"2026-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149013308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to: Paraneoplastic glomerulopathy associated with solid tumors: A review, [Crit. Rev. Oncol./Hematol. 227 (2026) 105550].","authors":"Mengsi Hu, Qiqi Ma, Liguang Wang, Zhimei Lv, Rong Wang","doi":"10.1016/j.critrevonc.2026.105576","DOIUrl":"https://doi.org/10.1016/j.critrevonc.2026.105576","url":null,"abstract":"","PeriodicalId":93958,"journal":{"name":"Critical reviews in oncology/hematology","volume":" ","pages":"105576"},"PeriodicalIF":5.6,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148892899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}