Biochimica et biophysica acta. Reviews on cancer最新文献

{"title":"Targeting metabolic cell death in cancer to reverse drug resistance.","authors":"Tingting Liu, Yixiong Dang, Wen Zhang, Yanting Liu, Yinghua Ji, Ping Lu, Haimin Zou, Wenyong Yang, Jingwen Jiang","doi":"10.1016/j.bbcan.2026.189737","DOIUrl":"10.1016/j.bbcan.2026.189737","url":null,"abstract":"<p><p>Evasion of apoptosis is a typical feature of malignant tumors developing to survive therapeutic stress. As a result, chemotherapeutic drugs that primarily induce apoptosis can no longer effectively kill tumor cells, which brings challenges to clinical cancer treatment. Recent evidence indicates that targeting key nodes in cellular metabolic pathways can bypass apoptotic routes and induce metabolic cell death in tumor cells to overcome drug resistance. Different from the traditional ways of defining cell death that rely on morphological features, metabolic cell death focuses more on the inducing factors and the associated dysregulation of cellular metabolic pathways. Metabolic cell death can be classified into four categories based on the driver factors of cell death: (1) metal ion dyshomeostasis-mediated cell death; (2) redox-collapse cell death; (3) pH dyshomeostasis-driven cell death; and (4) metabolic byproduct accumulation-mediated cell death. According to these metabolic cell death patterns, several therapeutic strategies targeting the metabolic vulnerabilities have attracted considerable attention. Here, we summarize the major metabolic cell death patterns of tumor cells, examine how these death modalities engage anti-tumor immunity, and discuss how exploiting them can reverse drug resistance. We further discuss the therapeutic window, tumor metabolic heterogeneity, and metabolic network therapeutic implications.</p>","PeriodicalId":93897,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":" ","pages":"189737"},"PeriodicalIF":8.3,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149208185","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":"Dynamic changes in the metabolic network and signalling pathways of cancer stem cells in therapy resistance.","authors":"Onyisi C Didamson, Sajan George, Heidi Abrahamse","doi":"10.1016/j.bbcan.2026.189738","DOIUrl":"https://doi.org/10.1016/j.bbcan.2026.189738","url":null,"abstract":"<p><p>Cancer stem cells (CSCs) play a pivotal role in therapeutic resistance, metastasis, and tumour recurrence. During treatment, these cells undergo dynamic changes that enable survival and metabolic adaptation, leading to poor clinical outcomes. CSCs are capable of developing resistance to drugs by alterations in the metabolic and signalling pathways. They exhibit metabolic adaptations that enable therapy resistance, tumour recurrence, and metastasis. These adaptations involve shifts in glycolysis, oxidative phosphorylation (OXPHOS), lipid and amino acid metabolism, mitochondrial dynamics, and interactions with the tumour microenvironment to support energy production. Depending on the biological contexts and the energy needs, CSCs can switch to different metabolic phenotypes. CSCs drive energy production and biogenesis via glycolysis in hypoxic conditions. OXPHOS is essential for sustaining cell dormancy, survival and carcinogenesis. In addition to glycolysis and OXPHOS, CSCs employ lipid metabolism for energy production via fatty acid oxidation and amino acids metabolism via glutamine metabolism promoting redox balancing and epigenetic modifications. Taken together, this metabolic plasticity facilitates CSC survival and treatment resistance. Besides, CSCs are capable of metabolically rewiring their niche to evade apoptosis, enhance DNA repair, and promote immune evasion, which are considered hallmarks of drug resistance and cancer relapse. An in-depth understanding of the metabolic network and signalling pathways of CSCs may help in developing combination or targeted therapies against them, thereby increasing the potential to formulate effective treatment approaches for the complete eradication of cancer/CSCs. This review addresses dynamic changes in the CSCs' metabolism and signalling leading to the development of drug-resistance phenotype, causing survival and relapse in the tumours. Therapeutic strategies targeting CSC metabolism and signalling via metabolic modulators and stemness inhibitor were discussed. Overall, CSC metabolic adaptation promotes drug resistance and tumour proliferation. Hence targeting these metabolic adaptations offers new perspective for the elimination of CSCs and enhanced therapy.</p>","PeriodicalId":93897,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":" ","pages":"189738"},"PeriodicalIF":8.3,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149198503","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":"Recent advances on AI-driven decoding of tertiary lymphoid structures in precision cancer immunotherapy.","authors":"Xu Sun, Rui Li, Daxu Zhang, Dingchang Li, Guanglong Dong","doi":"10.1016/j.bbcan.2026.189677","DOIUrl":"10.1016/j.bbcan.2026.189677","url":null,"abstract":"<p><p>Tertiary lymphoid structures (TLS) are organized ectopic immune aggregates within the tumor microenvironment and have been associated with prognosis and response to immunotherapy across multiple cancer types. However, their clinical interpretation cannot be reduced to a simple presence-or-absence assessment, and conventional histopathological evaluation is limited in reproducibility, scalability, and functional resolution. Recent advances in artificial intelligence (AI), digital pathology, spatial omics, and multiplex imaging provide new opportunities to quantify TLS morphology, maturity, spatial distribution, cellular composition, and therapy-associated changes. In this review, we summarize recent AI-based approaches for TLS detection, segmentation, maturity classification, multimodal integration, and non-invasive prediction, while also discussing their validation requirements and current limitations. We further examine TLS maturity as a functional continuum, highlighting the distinction between functionally active mature TLS and morphologically mature but functionally impaired \"pseudo-mature\" TLS. In addition, we discuss how proximal, distal, and therapy-remodeled TLS may have distinct biological and clinical implications. Finally, we outline a conceptual \"quantify-decode-intervene-reassess\" framework that links AI-assisted TLS assessment with spatial validation and emerging synthetic-immunology strategies. We emphasize that AI-derived TLS scores and the proposed TLS Functional Vitality Index remain investigational frameworks that require rigorous analytical, biological, and clinical validation before clinical deployment.</p>","PeriodicalId":93897,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":" ","pages":"189677"},"PeriodicalIF":8.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148687171","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":"Current strategies for innovative and experimental treatment: From cancer to senescence.","authors":"Maciej Wnuk, Anna Lewińska, María Moros","doi":"10.1016/j.bbcan.2026.189707","DOIUrl":"10.1016/j.bbcan.2026.189707","url":null,"abstract":"","PeriodicalId":93897,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":" ","pages":"189707"},"PeriodicalIF":8.3,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148984319","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":"The role of tissue factor in the tumor microenvironment and targeted therapy.","authors":"Ying Yan, Yifan Li, Dan Zou, Huanhuan Ma, Hao Chen","doi":"10.1016/j.bbcan.2025.189409","DOIUrl":"10.1016/j.bbcan.2025.189409","url":null,"abstract":"<p><p>Tissue factor (TF) serves as a pivotal initiator of coagulation and has been extensively acknowledged for its substantial involvement in cancer progression and metastasis. Recent evidence suggests that targeting TF can enhance the infiltration of immune effector cells, thereby reshape the tumor microenvironment (TME). Despite these advancements, a comprehensive review of TF's role within the TME has yet to be conducted. This review uniquely synthesizes emerging evidence on TF-mediated immunosuppression mechanisms and evaluates cutting-edge targeting strategies to overcome therapy resistance.</p>","PeriodicalId":93897,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":" ","pages":"189409"},"PeriodicalIF":8.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144801224","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":"Taurine and cancer: Biological properties and multifaceted roles in cancer progression.","authors":"Rong Liu, Xinze Li, Zhenyu Hua, ZhiTong Liu, ZhengYue Wang, Xiang Li","doi":"10.1016/j.bbcan.2025.189403","DOIUrl":"10.1016/j.bbcan.2025.189403","url":null,"abstract":"<p><p>Cancer remains one of the leading causes of mortality worldwide and poses a major threat to global health. Recent insights into the tumor microenvironment (TME) have highlighted the pivotal role of amino acid metabolism-one of the three core metabolic pathways-in driving tumor proliferation, metastasis, and resistance to therapy. Taurine, a conditionally essential amino acid abundantly present in various tissues, does not participate in protein synthesis but exhibits multiple biological functions, including antioxidant, anti-inflammatory, and cytoprotective effects. These properties are increasingly recognized as relevant in both physiological regulation and pathological conditions such as cancer. Emerging evidence suggests that taurine modulates tumor growth and progression through diverse mechanisms, including regulation of immune responses, redox homeostasis, cellular metabolism, and the TME. This review summarizes the multifaceted roles of taurine in tumorigenesis and its potential applications in cancer therapy, providing new perspectives for targeted intervention.</p>","PeriodicalId":93897,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":" ","pages":"189403"},"PeriodicalIF":8.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144762667","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":"The immunosuppressive microenvironment modulated by glioma-associated mesenchymal stem cells: Current status and potential strategies.","authors":"Yuyi Wu, Qiang Liu, Wei Xiang, Peng Fu","doi":"10.1016/j.bbcan.2025.189410","DOIUrl":"10.1016/j.bbcan.2025.189410","url":null,"abstract":"<p><p>Glioma, the most prevalent primary malignant tumor of the central nervous system, exhibits aggressive progression and poor prognosis, largely due to its highly immunosuppressive tumor microenvironment (TME). Glioma-associated mesenchymal stem cells (GA-MSCs), a key component of the glioma TME, play a dual and context-dependent role in tumor biology. On one hand, GA-MSCs actively shape immunosuppression by interacting with various immune cells-including T cells, B cells, natural killer (NK) cells, dendritic cells (DCs), and macrophages-via soluble factors (e.g., TGF-β, PGE2, miR-21) and cell-contact mechanisms, thereby facilitating tumor immune evasion. They also promote glioma progression by enhancing the stemness, invasiveness, and chemoresistance of glioma stem cells (GSCs) through pathways such as IL-6/STAT3 and mitochondrial transfer, while contributing to pathological angiogenesis via differentiation into pericytes and secretion of pro-angiogenic factors like VEGF. On the other hand, GA-MSCs possess therapeutic potential: genetically engineered GA-MSCs can secrete pro-inflammatory cytokines (e.g., IL-12, IFN-β) or immune checkpoint blockers (e.g., scFv-PD1) to reverse immunosuppression, serve as carriers for targeted delivery of chemotherapeutics, miRNAs, suicide genes, or oncolytic viruses, and enhance anti-tumor immune responses. However, clinical translation is hindered by challenges including residual immunosuppressive activity, unstable transgene expression, limited migration efficiency, and safety concerns. This review summarizes the complex mechanisms by which GA-MSCs modulate the glioma TME, highlights their bidirectional roles in tumor progression and immunotherapy, and discusses potential strategies to overcome current limitations, aiming to provide insights for developing novel therapies targeting GA-MSCs and their interactions within the glioma microenvironment.</p>","PeriodicalId":93897,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":" ","pages":"189410"},"PeriodicalIF":8.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144805427","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":"Decoding the key hallmarks of chemoresistance: A proteomic tale from breast cancer research.","authors":"Praneeta Pradip Bhavsar, Bhargab Kalita, Khushman Taunk, Srikanth Rapole","doi":"10.1016/j.bbcan.2025.189404","DOIUrl":"10.1016/j.bbcan.2025.189404","url":null,"abstract":"<p><p>Chemoresistance denotes the intricate, multifactorial molecular mechanisms by which malignant cells subvert the cytotoxicity of chemotherapeutic agents, thereby impeding therapeutic efficacy. This phenomenon is orchestrated through a confluence of processes, which we propose as the major hallmarks of chemoresistance in cancer. Dysregulation of drug transporters, activation of pro-survival pathways, cancer stem cell driven proliferation, DNA damage and repair mechanisms, evasion of apoptosis, autophagy induction, secretion of extracellular vesicles, and metabolic reprogramming represents the major mechanisms of chemoresistance in cancer. Breast cancer is one of the most common and aggressive types of cancer, with significant challenges in treatment due to its heterogeneity. Despite progress in various treatment regimens, chemoresistance continues to be a significant challenge in the effective management of breast cancer. In this context, high-throughput proteomic methodologies, which quantitatively assess proteome-wide alterations and explore post-translational modifications, can provide an unbiased framework for unraveling the molecular intricacies of chemotherapy resistance. This article comprehensively reviews the application of advanced proteomic techniques in elucidating the pathophysiological mechanisms of chemoresistance in breast carcer. Additionally, it highlights promising protein signatures uncovered via proteomic tools, as well as therapeutic strategies targeting chemoresistant hallmarks to overcome drug resistance in breast cancer. By leveraging the mightiness of proteomic technologies, we move closer to efficient, potent and personalized therapeutic interventions for chemoresistant breast cancer.</p>","PeriodicalId":93897,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":" ","pages":"189404"},"PeriodicalIF":8.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144765883","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":"Clinical aspect of combined immunotherapy and radiotherapy effect on tumor immune microenvironment in hepatobiliary and pancreatic cancers.","authors":"Jun-Jie Cheng, Qiu-Yi Zheng, Yi-Lan Huang, Yi-Xing Chen, Shi-Suo Du","doi":"10.1016/j.bbcan.2025.189406","DOIUrl":"10.1016/j.bbcan.2025.189406","url":null,"abstract":"<p><p>Hepatobiliary and pancreatic cancers (HBPCs) remain among the most aggressive nature and lethal malignancies, presenting formidable challenges in their treatment. Surgical resection remains the cornerstone of curative treatment for early-stage HBPCs; however, advanced cases often necessitate a multidisciplinary systematic approach incorporating radiotherapy and immunotherapy. In recent years, innovations in radiotherapy technology have facilitated the precise and targeted delivery of tumoricidal doses, minimizing damage to surrounding normal tissue and expanding the application of radiotherapy in treating HBPCs. Moreover, the intricate impact of radiotherapy on the tumor immune microenvironment (TIME) is being increasingly understood. Synergizing radiotherapy with immunotherapy to induce a robust and sustained antitumor immune response, both locally at the irradiated site and systemically throughout the body, represents a promising and increasingly critical avenue of current research. This review begins by delineating the heterogeneity of the TIME in HBPCs and discusses how radiotherapy can either stimulate or suppress the TIME under various conditions. It also highlights recent preclinical and clinical advances in combining radiotherapy with immunotherapy, which have shown potential in improving local control rates and inducing systemic antitumor responses. This emerging paradigm warrants sustained research to fully realize its therapeutic potential in HBPC management.</p>","PeriodicalId":93897,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":" ","pages":"189406"},"PeriodicalIF":8.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144769447","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":"Reprogramming of amino acid metabolism in breast cancer.","authors":"Meijin Wang, Yunlu Zhang, Zhenhua Li, Li Fu","doi":"10.1016/j.bbcan.2025.189412","DOIUrl":"10.1016/j.bbcan.2025.189412","url":null,"abstract":"<p><p>Breast cancer is one of the most prevalent malignant tumours, representing a significant health risk for women. Subtyping of breast cancer is based on gene expression profiles, with five distinct subtypes identified Luminal A, Luminal B, HER2-positive, basal-like and normal-like. The heterogeneity of breast cancer represents a significant challenge to its treatment, while drug resistance limits the effectiveness of existing therapies. There is widespread amino acid metabolic reprogramming in breast cancer, and the altered amino acid metabolism observed in breast cancer cells exhibits a heterogeneous metabolic phenotype that differs from normal cells. Consequently, targeting the metabolic differences between breast and normal cells may represent a promising novel anti-cancer strategy. In this article, we review the alterations in the metabolism of amino acids such as glutamine, cystine, serine, glycine, tryptophan and arginine in breast cancer and explore the specific mechanisms by which the aberrant expression of various amino acid metabolism-related enzymes leads to alterations in the proliferative, invasive and metastatic capacities of cancer cells. Finally, we summarise the drugs targeting amino acid metabolism in breast cancer that are currently in preclinical and clinical trials, providing a theoretical basis for targeted therapy of amino acid metabolism.</p>","PeriodicalId":93897,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":" ","pages":"189412"},"PeriodicalIF":8.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144805426","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}