Pub Date : 2026-02-06DOI: 10.1016/j.critrevonc.2026.105183
Zhenhao Wang , Hanlin Du , Zhuming Yang, Yuanyuan Zhang, Zhenya Hong
Recent studies have highlighted the pivotal role of lactate metabolism in key oncological processes, such as tumor proliferation, resistance and immune evasion. The discovery of histone lactylation pathways has further underscored the essential link between cellular energy metabolism and epigenetics, offering new insights into cancer biology. This review provides a systematic overview of lactate-immune crosstalk within the tumor microenvironment (TME), discusses the clinical relevance of lactate metabolism and lactylation biomarkers, and highlights emerging therapeutic strategies that target lactate-related pathways. By elucidating the lactate-regulated networks in cancer progression, this review offers insights into the underlying molecular mechanisms and potential pathways for the development of targeted therapies.
{"title":"The role of lactic acid metabolism in anti-tumor immunity","authors":"Zhenhao Wang , Hanlin Du , Zhuming Yang, Yuanyuan Zhang, Zhenya Hong","doi":"10.1016/j.critrevonc.2026.105183","DOIUrl":"10.1016/j.critrevonc.2026.105183","url":null,"abstract":"<div><div>Recent studies have highlighted the pivotal role of lactate metabolism in key oncological processes, such as tumor proliferation, resistance and immune evasion. The discovery of histone lactylation pathways has further underscored the essential link between cellular energy metabolism and epigenetics, offering new insights into cancer biology. This review provides a systematic overview of lactate-immune crosstalk within the tumor microenvironment (TME), discusses the clinical relevance of lactate metabolism and lactylation biomarkers, and highlights emerging therapeutic strategies that target lactate-related pathways. By elucidating the lactate-regulated networks in cancer progression, this review offers insights into the underlying molecular mechanisms and potential pathways for the development of targeted therapies.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"221 ","pages":"Article 105183"},"PeriodicalIF":5.6,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146144887","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}
Breast cancer (BC) is a highly heterogeneous malignancy and remains a major cause of cancer-related mortality among women worldwide. Advances in multi-omics profiling spanning genomics, transcriptomics, epigenomics, proteomics, and metabolomics have enabled finer subtype stratification and more comprehensive characterisation of tumour biology, thereby accelerating the discovery of diagnostic and prognostic biomarkers and actionable therapeutic targets. Nonetheless, translating multi-layer molecular signals into clinically robust decision support remains challenging because of the high dimensionality and heterogeneity of omics data, cross-cohort and cross-platform variability, and the fragmentation inherent to single-modality analyses. This review summarises how multi-omics studies have refined BC subtype definitions and advanced biomarker and target identification, and then synthesises recent progress in artificial intelligence, particularly deep learning, for integrating multi-omics with imaging, pathology, and clinical variables to improve diagnosis, risk stratification, prognosis prediction, and treatment response assessment. We critically examine representative multimodal integration frameworks and emerging deep learning architectures that learn both shared and modality-specific representations, which in many settings enable more accurate patient-level prediction than unimodal baselines. We further delineate key barriers to clinical translation, including cross-centre heterogeneity and inconsistent endpoint definitions, structural missingness of modalities in real-world workflows, inadequate cross-platform normalisation, limited interpretability and auditability, and a lack of prospective validation. Finally, we propose realistic next steps, including standardised and auditable preprocessing pipelines, missingness-aware fusion strategies, explainable and uncertainty-aware modelling, privacy-preserving multi-centre learning, and prospective, workflow-based evaluation. Collectively, these perspectives provide a roadmap for advancing multimodal AI–multi-omics integration toward reliable clinical deployment in BC management.
{"title":"Artificial intelligence and multi-omics convergence in breast cancer: Revolutionizing diagnosis, prognostication, and precision oncology","authors":"Bitao Jiang , Yuefei Wu , Xiao Chen , Chunyan Jian , Wenjuan Wang","doi":"10.1016/j.critrevonc.2026.105160","DOIUrl":"10.1016/j.critrevonc.2026.105160","url":null,"abstract":"<div><div>Breast cancer (BC) is a highly heterogeneous malignancy and remains a major cause of cancer-related mortality among women worldwide. Advances in multi-omics profiling spanning genomics, transcriptomics, epigenomics, proteomics, and metabolomics have enabled finer subtype stratification and more comprehensive characterisation of tumour biology, thereby accelerating the discovery of diagnostic and prognostic biomarkers and actionable therapeutic targets. Nonetheless, translating multi-layer molecular signals into clinically robust decision support remains challenging because of the high dimensionality and heterogeneity of omics data, cross-cohort and cross-platform variability, and the fragmentation inherent to single-modality analyses. This review summarises how multi-omics studies have refined BC subtype definitions and advanced biomarker and target identification, and then synthesises recent progress in artificial intelligence, particularly deep learning, for integrating multi-omics with imaging, pathology, and clinical variables to improve diagnosis, risk stratification, prognosis prediction, and treatment response assessment. We critically examine representative multimodal integration frameworks and emerging deep learning architectures that learn both shared and modality-specific representations, which in many settings enable more accurate patient-level prediction than unimodal baselines. We further delineate key barriers to clinical translation, including cross-centre heterogeneity and inconsistent endpoint definitions, structural missingness of modalities in real-world workflows, inadequate cross-platform normalisation, limited interpretability and auditability, and a lack of prospective validation. Finally, we propose realistic next steps, including standardised and auditable preprocessing pipelines, missingness-aware fusion strategies, explainable and uncertainty-aware modelling, privacy-preserving multi-centre learning, and prospective, workflow-based evaluation. Collectively, these perspectives provide a roadmap for advancing multimodal AI–multi-omics integration toward reliable clinical deployment in BC management.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"220 ","pages":"Article 105160"},"PeriodicalIF":5.6,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146077219","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}
Pub Date : 2026-01-26DOI: 10.1016/j.critrevonc.2026.105157
Wenxuan Fang , Junfang Du , Zedong Xu , Qiuyu Liu , Yonghong Liu , Xueni Wang
Death receptor 3 (DR3/TNFRSF25) is a member of the tumor necrosis factor receptor superfamily, exhibiting dual roles in regulating tumor apoptosis and metastasis. Through literature review and pan-cancer analysis, this study reveals that DR3 expression exhibits distinct tumor type specificity: it is highly expressed in seven cancers, including Bladder Urothelial Carcinoma (BLCA), while showing low expression in sixteen cancers, such as Adrenocortical carcinoma (ACC). Its expression correlates with CD8⁺ T cell and natural killer (NK) cell infiltration, tumor mutational burden (TMB), and is closely associated with prognosis, exhibiting opposite trends across different cancer types. Mechanistically, DR3 activates apoptosis or programmed necrosis pathways by binding its ligand TL1A. Its interaction with NF-κB exhibits directional discrepancies across cancer types, which differentially regulate cell death. Additionally, DR3 suppresses angiogenesis and modulates antitumor immune responses. While multiple natural and synthetic compounds modulate DR3-related pathways to exert antitumor effects, no direct-targeting drugs are currently available. The presence of DR3 isoforms and decoy receptor DcR3 adds complexity to its signaling, suggesting that future clinical applications require precise evaluation considering the tumor microenvironment. In summary, DR3 is a multifunctional molecule with significant potential as a biomarker and therapeutic target. However, its duality and context-dependent effects necessitate the development of personalized strategies based on tumor molecular subtyping.
{"title":"Death receptor 3: A paradoxical biomarker and therapeutic target in pan-cancer","authors":"Wenxuan Fang , Junfang Du , Zedong Xu , Qiuyu Liu , Yonghong Liu , Xueni Wang","doi":"10.1016/j.critrevonc.2026.105157","DOIUrl":"10.1016/j.critrevonc.2026.105157","url":null,"abstract":"<div><div>Death receptor 3 (DR3/TNFRSF25) is a member of the tumor necrosis factor receptor superfamily, exhibiting dual roles in regulating tumor apoptosis and metastasis. Through literature review and pan-cancer analysis, this study reveals that DR3 expression exhibits distinct tumor type specificity: it is highly expressed in seven cancers, including Bladder Urothelial Carcinoma (BLCA), while showing low expression in sixteen cancers, such as Adrenocortical carcinoma (ACC). Its expression correlates with CD8⁺ T cell and natural killer (NK) cell infiltration, tumor mutational burden (TMB), and is closely associated with prognosis, exhibiting opposite trends across different cancer types. Mechanistically, DR3 activates apoptosis or programmed necrosis pathways by binding its ligand TL1A. Its interaction with NF-κB exhibits directional discrepancies across cancer types, which differentially regulate cell death. Additionally, DR3 suppresses angiogenesis and modulates antitumor immune responses. While multiple natural and synthetic compounds modulate DR3-related pathways to exert antitumor effects, no direct-targeting drugs are currently available. The presence of DR3 isoforms and decoy receptor DcR3 adds complexity to its signaling, suggesting that future clinical applications require precise evaluation considering the tumor microenvironment. In summary, DR3 is a multifunctional molecule with significant potential as a biomarker and therapeutic target. However, its duality and context-dependent effects necessitate the development of personalized strategies based on tumor molecular subtyping.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"220 ","pages":"Article 105157"},"PeriodicalIF":5.6,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146077218","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}
Pub Date : 2026-01-26DOI: 10.1016/j.critrevonc.2026.105155
Xuefeng Jiang , Guotao Fang , Wen Li , Yusheng Liu , Gang Chen , Silvio E. Perea , Yasser Perera , Rong Ma , Xiaofei Hu , Xinan Long
Fatty acid synthase (FASN), the key enzyme driving de novo lipogenesis, has emerged as a central metabolic hub in cancer, linking aberrant lipid synthesis to tumor progression, immune escape, and therapy resistance. This review provides a comprehensive overview of the regulatory landscape and oncogenic functions of FASN, highlighting its modulation at transcriptional, post-transcriptional, and post-translational levels. We discuss how FASN-driven lipid remodeling supports tumor proliferation, disrupts antigen presentation, alters immune cell metabolism, and suppresses ferroptosis, thereby enabling resistance to chemotherapy, radiotherapy, targeted therapy, and immune checkpoint inhibitors. Emerging therapeutic strategies—including direct FASN inhibition, targeting upstream regulators, and rational metabolic–immune–ferroptosis combinatorial regimens—are explored in the context of precision oncology. Given the metabolic plasticity of cancer cells and the heterogeneous response of the tumor immune microenvironment, future advances will rely on dynamic biomarker-guided therapy and spatiotemporal profiling of FASN activity. Together, these insights position FASN not merely as a metabolic enzyme but as a versatile therapeutic axis at the intersection of cancer metabolism, immunity, and resistance.
{"title":"FASN at the crossroads of tumor metabolism, immune evasion, and therapy resistance: Mechanistic insights and therapeutic opportunities","authors":"Xuefeng Jiang , Guotao Fang , Wen Li , Yusheng Liu , Gang Chen , Silvio E. Perea , Yasser Perera , Rong Ma , Xiaofei Hu , Xinan Long","doi":"10.1016/j.critrevonc.2026.105155","DOIUrl":"10.1016/j.critrevonc.2026.105155","url":null,"abstract":"<div><div>Fatty acid synthase (FASN), the key enzyme driving de novo lipogenesis, has emerged as a central metabolic hub in cancer, linking aberrant lipid synthesis to tumor progression, immune escape, and therapy resistance. This review provides a comprehensive overview of the regulatory landscape and oncogenic functions of FASN, highlighting its modulation at transcriptional, post-transcriptional, and post-translational levels. We discuss how FASN-driven lipid remodeling supports tumor proliferation, disrupts antigen presentation, alters immune cell metabolism, and suppresses ferroptosis, thereby enabling resistance to chemotherapy, radiotherapy, targeted therapy, and immune checkpoint inhibitors. Emerging therapeutic strategies—including direct FASN inhibition, targeting upstream regulators, and rational metabolic–immune–ferroptosis combinatorial regimens—are explored in the context of precision oncology. Given the metabolic plasticity of cancer cells and the heterogeneous response of the tumor immune microenvironment, future advances will rely on dynamic biomarker-guided therapy and spatiotemporal profiling of FASN activity. Together, these insights position FASN not merely as a metabolic enzyme but as a versatile therapeutic axis at the intersection of cancer metabolism, immunity, and resistance.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"220 ","pages":"Article 105155"},"PeriodicalIF":5.6,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146077216","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}
Pub Date : 2026-01-25DOI: 10.1016/j.critrevonc.2026.105152
Qingliang Jiang , Gang Li , Hengyu Li , Xiaoqing Jiang , Daimin Xiang
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.
{"title":"Multifaceted mechanisms and precision strategies to overcome therapeutic resistance in gallbladder cancer","authors":"Qingliang Jiang , Gang Li , Hengyu Li , Xiaoqing Jiang , 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":"2026-01-25","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}
Pub Date : 2026-01-24DOI: 10.1016/j.critrevonc.2026.105153
Zuer He , Zijia Luo , Peilin Dai , Xiaoli Wang , Jiqiao Yang
Antibody-drug conjugates (ADCs) constitute an innovative category of anti-tumor therapeutics that selectively deliver cytotoxins to tumor cells, improving efficacy and reducing toxicity in comparison to systemic therapy. TROP2 serves as a significant target for ADCs in cancer detection and treatment. TROP2-targeted ADCs have shown promising efficacy in cancer therapy. However, it is essential to monitor expected adverse effects to ensure the anti-tumor efficacy and safety. This review clarifies the mechanisms and toxicological profiles of TROP2-targeted medicines based on clinical trials and recommendations, with the aim of providing solutions for the prevention, detection, and management of related adverse events.
{"title":"Management of adverse events associated with TROP2-targeted antibody-drug conjugates in cancer patients","authors":"Zuer He , Zijia Luo , Peilin Dai , Xiaoli Wang , Jiqiao Yang","doi":"10.1016/j.critrevonc.2026.105153","DOIUrl":"10.1016/j.critrevonc.2026.105153","url":null,"abstract":"<div><div>Antibody-drug conjugates (ADCs) constitute an innovative category of anti-tumor therapeutics that selectively deliver cytotoxins to tumor cells, improving efficacy and reducing toxicity in comparison to systemic therapy. TROP2 serves as a significant target for ADCs in cancer detection and treatment. TROP2-targeted ADCs have shown promising efficacy in cancer therapy. However, it is essential to monitor expected adverse effects to ensure the anti-tumor efficacy and safety. This review clarifies the mechanisms and toxicological profiles of TROP2-targeted medicines based on clinical trials and recommendations, with the aim of providing solutions for the prevention, detection, and management of related adverse events.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"220 ","pages":"Article 105153"},"PeriodicalIF":5.6,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146055352","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}
Pub Date : 2026-01-23DOI: 10.1016/j.critrevonc.2026.105154
Amirhossein Shahsavand , Shayan Forghani , Mohammad Amin Kharaghani , Reza Samiee , Rania A. Mekary , Mohammad Mahdi Aliasghari , Sajjad Fattahnia , Mona Daghaieghi , Mohammad Reza Rostami , Tahereh Rostami , Ghasem Janbabai
Over 20 % of patients with Hodgkin lymphoma (HL) experience disease progression after initial treatment. We evaluated the prognostic utility of circulating tumor DNA (ctDNA) in HL patients. We systematically searched PubMed, Embase, the Cochrane Library, Scopus, and Web of Science up to March 22, 2025. Survival data were extracted from Kaplan–Meier curves and digitized to reconstruct individual patient-level datasets. We applied a hierarchical Bayesian model with weakly informative priors to estimate hazard ratios (HRs), restricted mean survival times (RMSTs), along with their 95 % credible intervals (CrI) up to five years for both progression-free survival (PFS) and overall survival (OS). Ten studies, including 1158 patients, were analyzed. Elevated baseline ctDNA was associated with inferior PFS (HR: 2.74; 95 % CrI: 1.30–5.75) and a 5-year RMST loss of 7.7 (1.2–17.3) months. Prognostic strength increased over time, with interim ctDNA positivity showing an HR of 5.99 (3.46–10.13; ΔRMST: 22.7 months; 12.9–33.2) and end-of-treatment ctDNA positivity showing an HR of 13.4 (3.97–41.87; ΔRMST: 39.2 months; 17.7–49.4). High baseline ctDNA was associated with worse OS (HR: 2.49; 1.07–5.80; ΔRMST: 11.6 months; 0.7–27.8). Similarly, positive ctDNA following treatment predicted worse OS (HR: 4.74; 1.60–14.47; ΔRMST: 16.2 months; 3.0–38.1). To conclude, in HL patients, a higher ctDNA concentration was associated with increased disease progression and mortality, with this association intensifying toward the end-of-treatment. Clinical implementation requires standardization of assay methods, validation of prognostic thresholds, and longitudinal assessment of the independent prognostic value of ctDNA.
{"title":"Prognostic utility of circulating tumor DNA in classical hodgkin lymphoma: A systematic review and individual participant data bayesian meta-analysis","authors":"Amirhossein Shahsavand , Shayan Forghani , Mohammad Amin Kharaghani , Reza Samiee , Rania A. Mekary , Mohammad Mahdi Aliasghari , Sajjad Fattahnia , Mona Daghaieghi , Mohammad Reza Rostami , Tahereh Rostami , Ghasem Janbabai","doi":"10.1016/j.critrevonc.2026.105154","DOIUrl":"10.1016/j.critrevonc.2026.105154","url":null,"abstract":"<div><div>Over 20 % of patients with Hodgkin lymphoma (HL) experience disease progression after initial treatment. We evaluated the prognostic utility of circulating tumor DNA (ctDNA) in HL patients. We systematically searched PubMed, Embase, the Cochrane Library, Scopus, and Web of Science up to March 22, 2025. Survival data were extracted from Kaplan–Meier curves and digitized to reconstruct individual patient-level datasets. We applied a hierarchical Bayesian model with weakly informative priors to estimate hazard ratios (HRs), restricted mean survival times (RMSTs), along with their 95 % credible intervals (CrI) up to five years for both progression-free survival (PFS) and overall survival (OS). Ten studies, including 1158 patients, were analyzed. Elevated baseline ctDNA was associated with inferior PFS (HR: 2.74; 95 % CrI: 1.30–5.75) and a 5-year RMST loss of 7.7 (1.2–17.3) months. Prognostic strength increased over time, with interim ctDNA positivity showing an HR of 5.99 (3.46–10.13; ΔRMST: 22.7 months; 12.9–33.2) and end-of-treatment ctDNA positivity showing an HR of 13.4 (3.97–41.87; ΔRMST: 39.2 months; 17.7–49.4). High baseline ctDNA was associated with worse OS (HR: 2.49; 1.07–5.80; ΔRMST: 11.6 months; 0.7–27.8). Similarly, positive ctDNA following treatment predicted worse OS (HR: 4.74; 1.60–14.47; ΔRMST: 16.2 months; 3.0–38.1). To conclude, in HL patients, a higher ctDNA concentration was associated with increased disease progression and mortality, with this association intensifying toward the end-of-treatment. Clinical implementation requires standardization of assay methods, validation of prognostic thresholds, and longitudinal assessment of the independent prognostic value of ctDNA.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"219 ","pages":"Article 105154"},"PeriodicalIF":5.6,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146047631","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}
Pub Date : 2026-01-23DOI: 10.1016/j.critrevonc.2026.105151
Chaonan He , Xianghao Dai , Dongyu Feng , Qi Zhou , Wenhong Liu , Ye Xu , Fangfang Tao , Mengjiao Hu
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.
{"title":"Cancer-associated thrombosis in the era of precision oncology: Mechanisms, challenges and future directions","authors":"Chaonan He , Xianghao Dai , Dongyu Feng , Qi Zhou , Wenhong Liu , Ye Xu , Fangfang Tao , 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":"2026-01-23","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}
Neuregulin 1 (NRG1) 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 NRG1 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 NRG1 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.
{"title":"NRG1 fusions：The potential targeted treatment in non-small cell lung cancer(NSCLC)","authors":"Jiantao Zhang , Xiaonu Peng , Haibo Huang, 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":"2026-01-23","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}
Pub Date : 2026-01-23DOI: 10.1016/j.critrevonc.2026.105150
Yuanhao Lv , Ziyin Zhao , Wenyu Di , Lei Liu , Yiyang Chen , Wei Su , Yinghua Ji , Jiateng Zhong
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.
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