Critical reviews in oncology/hematology最新文献

{"title":"Cancer-associated thrombosis in the era of precision oncology: Mechanisms, challenges and future directions","authors":"Chaonan He ,&nbsp;Xianghao Dai ,&nbsp;Dongyu Feng ,&nbsp;Qi Zhou ,&nbsp;Wenhong Liu ,&nbsp;Ye Xu ,&nbsp;Fangfang Tao ,&nbsp;Mengjiao Hu","doi":"10.1016/j.critrevonc.2026.105151","DOIUrl":"10.1016/j.critrevonc.2026.105151","url":null,"abstract":"<div><div>Cancer-associated thrombosis (CAT) is a common and life-threatening complication in cancer patients, leading to poor prognosis and reduced survival rate. The pathophysiology process of CAT is driven by a complex interplay of tumor-related process, including tumor-specific genetic mutations, activation of coagulation cascades, multicellular interactions within the tumor microenvironment, and suppression of the fibrinolytic system. Moreover, anticancer therapies, particularly immune checkpoint inhibitors have been shown to further exacerbate this risk. A profound understanding of these mechanisms is essential for therapeutic advancement, necessitating robust preclinical models that accurately replicate the complex pathological features of the disease. This review synthesizes the core mechanisms of CAT, critically evaluates the strategic application of current CAT models, and highlights recent advances in predictive biomarkers, risk assessment models, and emerging therapeutic targets. By integrating mechanistic insights with translational challenges, this review seeks to inform and guide the development of more effective, targeted interventions for CAT.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"219 ","pages":"Article 105151"},"PeriodicalIF":5.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146047576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intratumoral microbiota: Distribution, mechanisms, and therapeutic implications","authors":"Jiafei Ge ,&nbsp;Lulu Gao ,&nbsp;Lin Yu","doi":"10.1016/j.critrevonc.2026.105128","DOIUrl":"10.1016/j.critrevonc.2026.105128","url":null,"abstract":"<div><div>Recent studies have increasingly highlighted the presence of microbiota within tumors and their substantial impact on tumor initiation, progression, and treatment efficacy. Intratumoral microbiota modulate tumor progression via multiple mechanisms, such as regulation of cancer cell proliferation, manipulation of immune microenvironment, and induction of the DNA damage. Notably, the distinct bacterial profiles associated with each tumor type can, in turn, promote or suppress tumor growth. Given the various mechanisms through which intratumoral microbiota influence tumor progression, a deeper understanding of their composition and functional roles in tumor dynamics is critical for the development of targeted therapies. In this review, we summarize current understanding and future perspectives of the bacterial lineages associated with different tumor types, discuss the mechanisms through which the intratumoral microbiome modulates tumor progression, and highlight emerging therapeutic strategies targeting intratumoral bacteria, including sonodynamic therapy (SDT), chemotherapy, immunotherapy, and oncolytic bacterial approaches.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"219 ","pages":"Article 105128"},"PeriodicalIF":5.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145992324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NRG1 fusions：The potential targeted treatment in non-small cell lung cancer(NSCLC)","authors":"Jiantao Zhang ,&nbsp;Xiaonu Peng ,&nbsp;Haibo Huang,&nbsp;Zheng Zhang","doi":"10.1016/j.critrevonc.2026.105147","DOIUrl":"10.1016/j.critrevonc.2026.105147","url":null,"abstract":"<div><div>Neuregulin 1 (<em>NRG1</em>) gene fusions represent a rare but clinically actionable oncogenic driver in non-small cell lung cancer (NSCLC). This review synthesizes recent advances in targeted therapies for <em>NRG1</em> fusion-positive NSCLC, with a focus on the underlying molecular mechanisms, diagnostic methodologies, and emerging clinical evidence. Current evidence demonstrates the therapeutic potential of various approaches, including HER3-directed monoclonal antibodies, pan-HER tyrosine kinase inhibitors (TKIs), HER2-selective TKIs, and novel bispecific antibodies. Clinical data have reported partial responses in approximately 35–40 % of patients treated with HER3-targeted agents, accompanied by a median progression-free survival ranging from 4.6 to 6.2 months. Critical challenges persist, such as intrinsic resistance mediated by the heterogeneity of <em>NRG1</em> fusion isoforms and compensatory activation of the epidermal growth factor receptor (EGFR) pathway. This comprehensive analysis underscores the unmet need for novel therapeutics and provides a framework for optimizing precision oncology strategies in this molecularly defined NSCLC subset, highlighting the necessity for standardized diagnostic protocols and globally collaborative clinical trials.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"219 ","pages":"Article 105147"},"PeriodicalIF":5.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146047662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Explainable artificial intelligence for multi-modal cancer analysis: From genomics to immunology","authors":"Min Zhang ,&nbsp;Lina Yin","doi":"10.1016/j.critrevonc.2025.105040","DOIUrl":"10.1016/j.critrevonc.2025.105040","url":null,"abstract":"<div><div>Cancer remains one of the most biologically intricate and heterogeneous diseases, with variability spanning genetic, epigenetic, metabolic, spatial, and immunological dimensions. This multifactorial complexity is shaped by tumor-microenvironment interactions, immune modulation, clonal evolution, and therapeutic pressures, creating profound challenges for accurate prognosis, treatment selection, and durable response prediction. Conventional single-modality analytical approaches often capture only isolated features of this landscape, limiting their ability to generalize across patient populations and clinical settings. Selective multimodal deep learning (MDL) provides a transformative framework by mechanism-informed integration of complementary biomedical data—including genomics, transcriptomics, histopathology, medical imaging, proteomics, metabolomics, electronic health records (EHRs), and immunological profiles into unified models capable of capturing cross-scale dependencies and emergent patterns, while mitigating interference through targeted fusion strategies. The interpretability of these models is enhanced by explainable artificial intelligence (XAI), which translates complex computational predictions into transparent, biologically grounded explanations that align with known oncological and immunological processes. A distinctive focus of this review is immunology-informed integration, which connects predictive signatures to tumor–immune microenvironment dynamics, enhancing biomarker discovery, immunotherapy stratification, and hypothesis generation. We review key foundations, fusion strategies, and explainability methods in precision oncology, emphasizing rigorous validation frameworks that include statistical metrics and biological plausibility assessments. We address challenges such as data harmonization and modality imbalance, and discuss criteria for selecting modalities to ensure scientific validity. Finally, we outline future directions like federated learning for privacy, causal inference-driven explainability, and patient-specific digital twins, all aimed at advancing personalized precision oncology.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"219 ","pages":"Article 105040"},"PeriodicalIF":5.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145607950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multifaceted mechanisms and precision strategies to overcome therapeutic resistance in gallbladder cancer","authors":"Qingliang Jiang ,&nbsp;Gang Li ,&nbsp;Hengyu Li ,&nbsp;Xiaoqing Jiang ,&nbsp;Daimin Xiang","doi":"10.1016/j.critrevonc.2026.105152","DOIUrl":"10.1016/j.critrevonc.2026.105152","url":null,"abstract":"<div><div>Gallbladder cancer (GBC) is a rare but highly aggressive malignancy with poor prognosis, largely due to the pervasive challenge of therapeutic resistance. Conventional chemotherapy, targeted therapy, and immunotherapy have shown limited efficacy, as tumor cells rapidly acquire resistance through diverse mechanisms. These include drug metabolism reprogramming, enhanced DNA damage repair, signaling pathway rewiring, epigenetic and non-coding RNA regulation, programmed cell death modulation, immune evasion, and remodeling of the TME. Increasing evidence indicates that resistance in GBC is not driven by a single factor but rather by the dynamic interplay between intrinsic tumor heterogeneity and extrinsic microenvironmental influences. To overcome these barriers, emerging strategies such as multi-target combination regimens, functionalized nanodelivery systems, tumor penetration enhancers, and microbiota-based interventions have demonstrated encouraging potential in preclinical and translational studies. This review provides a comprehensive overview of the multidimensional mechanisms of resistance in GBC and highlights current and emerging strategies aimed at reversing or bypassing these processes. A deeper understanding of key resistance nodes and the rational design of cross-pathway interventions will be essential for improving therapeutic efficacy and long-term survival in patients with GBC.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"219 ","pages":"Article 105152"},"PeriodicalIF":5.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146069190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding the role of LRP1 in cancers: From molecular mechanisms to therapeutic opportunities","authors":"Dan Zou ,&nbsp;Jike Hu ,&nbsp;Yunpeng Wang ,&nbsp;Puyi He ,&nbsp;Lei Gao ,&nbsp;Huanhuan Ma ,&nbsp;Ying Yan ,&nbsp;Yifan Li ,&nbsp;Kai Wang ,&nbsp;Weiyi Chen ,&nbsp;Bofang Wang ,&nbsp;Xiaotong Wang ,&nbsp;Hao Chen","doi":"10.1016/j.critrevonc.2026.105122","DOIUrl":"10.1016/j.critrevonc.2026.105122","url":null,"abstract":"<div><div>Low-density lipoprotein receptor-related protein 1 (LRP1), a key member of the Low-density lipoprotein receptor (LDLR) family, is a transmembrane receptor with a wide range of biological functions. It plays a crucial regulatory role in physiological processes such as lipid metabolism, extracellular matrix remodeling, and cell signal transduction. Recent studies have highlighted that LRP1 also plays a significant role in tumorigenesis by influencing tumor progression through its involvement in regulating tumor cell invasion and metastasis, angiogenesis, immune evasion, and metabolic reprogramming. However, the precise molecular mechanisms underlying these processes remain to be further elucidated. This review systematically summarizes the current understanding of LRP1's functional role across various tumor types, with particular emphasis on its regulatory mechanisms in tumor malignancy and the tumor microenvironment. Additionally, its involvement in treatment resistance and potential applications in drug delivery for brain tumors are discussed. This review aims to provide a theoretical basis for the development of LRP1 as a novel therapeutic target in cancer treatment and its potential translation into precision medicine.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"219 ","pages":"Article 105122"},"PeriodicalIF":5.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145992382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neoadjuvant therapy in ovarian cancer: Emerging paradigms and therapeutic frontiers","authors":"Yuxuan Shi ,&nbsp;Wei Xiong ,&nbsp;Bairong Xia","doi":"10.1016/j.critrevonc.2025.105065","DOIUrl":"10.1016/j.critrevonc.2025.105065","url":null,"abstract":"<div><div>The use of neoadjuvant therapy followed by intermittent tumor cytoreduction has emerged as an effective treatment for advanced ovarian cancer patients with high tumor load and poor physical status. Research on specific dosing regimens for neoadjuvant therapy has continued to gain momentum in recent years, involving the optimization of conventional chemotherapy regimens, the introduction of targeted agents and immunotherapies, and single-agent or multi-agent combination strategies. The purpose of this review is to provide a comprehensive review of these recent advances, with the aim of providing valuable references and bases for the clinical treatment of advanced ovarian cancer.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"219 ","pages":"Article 105065"},"PeriodicalIF":5.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145746134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"KRAS mutations reshape the immunosuppressive tumor microenvironment in triple-negative breast cancer: A novel perspective","authors":"Yuanhao Lv ,&nbsp;Ziyin Zhao ,&nbsp;Wenyu Di ,&nbsp;Lei Liu ,&nbsp;Yiyang Chen ,&nbsp;Wei Su ,&nbsp;Yinghua Ji ,&nbsp;Jiateng Zhong","doi":"10.1016/j.critrevonc.2026.105150","DOIUrl":"10.1016/j.critrevonc.2026.105150","url":null,"abstract":"<div><div>Triple-negative breast cancer (TNBC) is an aggressive subtype characterized by poor prognosis and limited therapeutic options due to the lack of well-defined molecular targets. While conventional studies have primarily focused on tumor cell-intrinsic oncogenic mechanisms, this article presents a novel perspective emphasizing the pivotal role of KRAS mutations in remodeling the tumor microenvironment (TME) of TNBC. Although KRAS mutations are relatively uncommon in TNBC (approximately 2–5 %), their presence is associated with increased tumor aggressiveness, the establishment of an immunosuppressive microenvironment, and poor clinical outcomes. This review systematically explores how KRAS mutations, potentially through the modulation of NADPH oxidase 2 (NOX2) activity, may alter oxidative stress dynamics within the TME. We propose that this axis impairs immune cell function, facilitating immune evasion and therapeutic resistance. This perspective not only deepens our understanding of the mechanisms underlying the malignant progression of TNBC but also provides a theoretical basis for developing novel therapeutic strategies to overcome current treatment challenges.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"219 ","pages":"Article 105150"},"PeriodicalIF":5.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146047656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TRAIL-functionalized nanoparticles in cancer therapy: Molecular mechanisms and translational opportunities","authors":"Dasari Sahithi ,&nbsp;Urushi Rehman ,&nbsp;Ramasubbamma Ramaiah ,&nbsp;Umme Hani ,&nbsp;Garima Gupta ,&nbsp;Khang Wen Goh ,&nbsp;Prashant Kesharwani","doi":"10.1016/j.critrevonc.2026.105149","DOIUrl":"10.1016/j.critrevonc.2026.105149","url":null,"abstract":"<div><div>Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potent anticancer agent capable of selectively triggering apoptosis in malignant cells while sparing normal tissues. Clinical translation of TRAIL is limited by rapid systemic clearance, poor pharmacokinetics, and intrinsic or acquired tumor resistance. Nanotechnology offers innovative solutions by stabilizing TRAIL, enhancing bioavailability, and enabling targeted delivery. Lipid-based, polymeric, and metallic nanoparticles have been engineered to improve TRAIL activity and achieve tumor-specific accumulation. TRAIL-functionalized nanocarriers also facilitate combinatorial strategies, including co-delivery with chemotherapeutics, sensitizers, or immunomodulators, to overcome resistance and potentiate apoptotic signaling. Preclinical studies in triple-negative breast cancer, glioblastoma, and colorectal carcinoma models demonstrate enhanced therapeutic efficacy, reduced systemic toxicity, and significant translational potential. This review critically examines the molecular mechanisms of TRAIL-mediated apoptosis, design principles of TRAIL-conjugated nanoparticles, and their integration into synergistic therapeutic regimens. Current limitations and future directions are discussed, emphasizing strategies to advance TRAIL nanomedicines toward clinical application. Collectively, TRAIL-functionalized nanoparticles represent a promising approach to precision oncology, bridging molecular therapeutics and nanotechnology for personalized cancer treatment.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"219 ","pages":"Article 105149"},"PeriodicalIF":5.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146047597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial intelligence applications in ovarian cancer detection: A systematic literature review of deep learning approaches and clinical translation challenges","authors":"Burak Gülmez","doi":"10.1016/j.critrevonc.2026.105126","DOIUrl":"10.1016/j.critrevonc.2026.105126","url":null,"abstract":"<div><div>This systematic literature review examines artificial intelligence applications in ovarian cancer detection through analysis of 61 studies published between 2020 and 2025. The investigation reveals advancing methodological sophistication alongside persistent limitations constraining clinical translation. Convolutional neural network architectures dominate current research, with ResNet variants achieving accuracy rates between 92 % and 99.7 %. Vision transformer integration demonstrates competitive performance while providing attention-based interpretability mechanisms. Ensemble methodologies produce superior diagnostic accuracy, reaching 98.96 % through multi-model integration strategies. Dataset heterogeneity presents barriers to model generalizability, with sample sizes ranging from hundreds to thousands of images and private institutional datasets limiting external validation opportunities. Hyperparameter optimization receives minimal attention across reviewed studies, with twelve investigations implementing systematic parameter tuning. Explainable AI implementation occurs in seven studies despite growing regulatory requirements for transparent medical AI systems. Object detection applications demonstrate limited adoption compared to classification approaches, with U-Net variants comprising the primary segmentation methodology. Bibliometric analysis indicates increasing research activity, with publication counts rising from 5 papers in 2020–2021, 34 papers in 2023–2024. Future research directions should prioritize standardization initiatives for data collection and evaluation metrics, prospective clinical trials for validation, and regulatory pathway development for medical AI system approval.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"219 ","pages":"Article 105126"},"PeriodicalIF":5.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145992321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}