Biochimica et biophysica acta. Reviews on cancer最新文献

{"title":"Emerging perspectives on metabolic reprogramming in the microenvironment of ovarian cancer metastasis","authors":"Jing Ma ,&nbsp;Sally K.Y. To ,&nbsp;Xinyu Zhang ,&nbsp;Weiyang Zhao ,&nbsp;Peng Zhang ,&nbsp;Alice S.T. Wong","doi":"10.1016/j.bbcan.2026.189554","DOIUrl":"10.1016/j.bbcan.2026.189554","url":null,"abstract":"<div><div>Ovarian cancer (OC) is one of the most lethal malignancies in females, mainly due to the aggressive metastasis at the late stage and the unsatisfactory of current therapies. OC cells exhibit a special metastatic behavior compared to other common epithelial tumors, primarily spreading within the peritoneal cavity. Due to the complexity of tumor microenvironment, physical factors induce significant metabolic changes in OC cells, thereby enhancing their metastatic ability. Key cellular components, such as cancer-associated fibroblasts and adipocytes, act synergistically to support metastasis through metabolic interactions. Recent efforts in tumor immunometabolism showed that metabolic reprogramming of immune cells can also significantly impact metastatic progression. Moreover, the microbiome and cellular senescence are emerging as important factors that alter the metabolic landscape. This review provides a systematic review of metabolic reprogramming in the OC microenvironment and highlights the most recent clinical trials targeting metabolic pathways. By increasing our understanding of these metabolic interactions, we can develop innovative metabolism-targeting interventions for this devastating gynecological malignancy.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1881 2","pages":"Article 189554"},"PeriodicalIF":9.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146168431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The interplay between cytokines and immune checkpoints in breast cancer therapy","authors":"Ying Wu ,&nbsp;Yin Zhu ,&nbsp;Qing Cang ,&nbsp;Zakari Shaibu ,&nbsp;Lifeng Kong ,&nbsp;Qi Zhou ,&nbsp;Xinxin Li ,&nbsp;Liang Yin","doi":"10.1016/j.bbcan.2026.189539","DOIUrl":"10.1016/j.bbcan.2026.189539","url":null,"abstract":"<div><div>Breast cancer (BC) immunotherapy has transformed treatment paradigms, yet response rates remain limited by the complex interplay between cytokine networks and immune checkpoints. This review synthesizes emerging evidence on how cytokines dynamically regulate immune checkpoint expression and function within the breast tumor microenvironment. We examine pro-tumorigenic cytokine circuits alongside immunostimulatory pathways. A key focus is the subtype-specific nature of these interactions, with triple-negative breast cancers (TNBC) exhibiting distinct cytokine-checkpoint crosstalk compared to hormone receptor-positive subtypes. The review highlights innovative therapeutic strategies, including cytokine-targeting agents in clinical trials and engineered approaches like spatial-targeted nanocarriers. We further discuss how cutting-edge technologies from single-cell RNA sequencing to spatial proteomics are revealing novel biomarker opportunities. By decoding these intricate immune dialogues, this review provides a framework for developing precision immunotherapy combinations tailored to BC immunological heterogeneity.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1881 2","pages":"Article 189539"},"PeriodicalIF":9.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146042290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heterogeneous neutrophils: Key players in regulating tumor immunity","authors":"Wenchao Bi ,&nbsp;Xue Li ,&nbsp;Huajun Zhao ,&nbsp;Qiuju Han ,&nbsp;Jian Zhang","doi":"10.1016/j.bbcan.2026.189538","DOIUrl":"10.1016/j.bbcan.2026.189538","url":null,"abstract":"<div><div>As the most abundant innate immune cells in bone marrow and peripheral blood, neutrophils were once considered functionally homogeneous and exerted inflammatory and anti-infection functions. However, emerging evidence reshapes the perception of neutrophils from passive effectors to dynamic regulators with high plasticity and heterogeneity, especially within the tumor microenvironment (TME). This review summarizes recent advances, particularly driven by single-cell technologies, demonstrating that tumor-associated neutrophils (TANs) represent a continuum of distinct functional states originating from heterogeneous developmental pathways in bone marrow, circulation and spleen. We classified TANs into diverse subsets based on unique molecular signatures and functions, including pro-tumor, inflammatory, interferon-stimulated genes (ISGs)^high, and antigen-presenting subsets, and highlighted that TANs profoundly impacting tumor progression through distinct molecular mechanisms. Importantly, we delineate how TANs functionally interact with T cells, NK cells, macrophages and other immune cells, revealing the pivotal role of TANs in reconfiguring immune response networks to modulate tumor progression. Lastly, we discuss emerging therapeutic strategies targeting TAN recruitment, reprogramming, or specific pro-tumor subsets to overcome therapy resistance, aiming to provide insights for future research directions on neutrophils and the development of neutrophil-targeted cancer therapeutic strategies.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1881 2","pages":"Article 189538"},"PeriodicalIF":9.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146031809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current landscape of PDT-based combination therapy for cutaneous squamous cell carcinoma: From molecular mechanisms to clinical practice","authors":"Ziwei Kang ,&nbsp;Guorong Yan ,&nbsp;Guolong Zhang","doi":"10.1016/j.bbcan.2026.189541","DOIUrl":"10.1016/j.bbcan.2026.189541","url":null,"abstract":"<div><div>Photodynamic therapy (PDT) has been extensively applied in the management of superficial cutaneous squamous cell carcinoma (cSCC). However, the efficacy of PDT was limited by issues including poor tissue penetration and hypoxia. In recent years, to enhance the effectiveness of PDT in cSCC, various combination strategies have been derived. Here, we revisit the basic mechanism of PDT and summarize clinical and basic researches of PDT-based combination strategies in treating cSCC, including topical agents, systemic therapies, and physical interventions. Evidences indicate that most of these combination approaches significantly enhanced the efficacy of PDT and leveraged three primary synergistic mechanisms: enhanced photosensitizer accumulation and delivery, potentiated tumor cell death, and augmented anti-tumor immunity. Future research should focus on optimizing light dosimetry, validating combination protocols in large clinical trials, and developing more tumor-targeted photosensitizers to improve PDT's clinical outcomes.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1881 2","pages":"Article 189541"},"PeriodicalIF":9.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146044344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SCF-FBXO31 E3 ubiquitin ligase in cancer: Molecular insights and clinical implications","authors":"Osheen Sahay ,&nbsp;Abhayananda Behera ,&nbsp;Chandra Biswas ,&nbsp;Ganesh Kumar Barik ,&nbsp;Sehbanul Islam","doi":"10.1016/j.bbcan.2026.189534","DOIUrl":"10.1016/j.bbcan.2026.189534","url":null,"abstract":"<div><div>F-box only protein 31 (FBXO31), a substrate adapter of SKP1-Cullin1-F-box (SCF) E3 ubiquitin ligase, was first identified as a candidate tumor suppressor in breast cancer due to its role in inducing senescence. Over the past two decades, FBXO31 has emerged as a crucial regulator in several human cancers, where it promotes the proteasomal degradation of various oncoproteins. FBXO31 plays a crucial role in regulating the cell cycle to maintain genomic integrity and inhibits processes such as epithelial-to-mesenchymal transition (EMT), invasion, and metastasis. This review examines the molecular mechanisms underlying the potent tumor-suppressive functions of FBXO31 in diverse human cancers. We also discuss the underlying causes of FBXO31 deregulation in cancer, providing insights into the intricate regulatory networks governing its expression. Additionally, we also examine the unexpected oncogenic functions of FBXO31 in certain cellular contexts. Finally, we highlight the clinical potential of FBXO31 in human malignancies, discussing its implications as both a biomarker and a therapeutic target. In conclusion, understanding the nuanced biology of FBXO31 is crucial for unravelling its role in tumorigenesis and advancing future therapeutic strategies.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1881 2","pages":"Article 189534"},"PeriodicalIF":9.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146004671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Organic nanoplatforms for metallodrugs delivery: Current advances in colorectal cancer","authors":"Íris Neto ,&nbsp;João Rocha ,&nbsp;Maria Manuela Gaspar ,&nbsp;Catarina P. Reis","doi":"10.1016/j.bbcan.2026.189547","DOIUrl":"10.1016/j.bbcan.2026.189547","url":null,"abstract":"<div><div>Colorectal cancer (CRC) represents a formidable global health challenge, with over 1.14 million new cases and 538,000 deaths estimated in 2022. The multifactorial nature of CRC carcinogenesis limits conventional therapies, thus demanding innovative treatment approaches. Metallodrugs have emerged as promising anticancer agents due to their unique physicochemical properties and unique mechanisms of action. However, their clinical translation is hindered by poor aqueous solubility, limited stability, and significant systemic toxicity.</div><div>This comprehensive review examines the integration of organic nanoparticles and biomimetic smart nanocarriers to overcome metallodrug limitations in CRC therapy. We systematically analyse three major nanocarrier classes: lipid-based systems, protein-based platforms, and polymeric carriers. Critical evaluation criteria encompass synthesis complexity, scalability, biocompatibility, and translational feasibility. Each nanocarrier offers exclusive advantages: liposomes provide clinical maturity, protein nanoparticles present exceptional biocompatibility, and polymeric systems enable superior customization. Current preclinical successes demonstrate remarkable therapeutic improvements, with several candidates advancing to clinical evaluation. Although widespread impact is expected to happen gradually, ongoing developments continue to show promise. Advances in manufacturing scalability and long-term safety will be some critical points for the progress of these nanotherapeutic strategies for CRC management.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1881 2","pages":"Article 189547"},"PeriodicalIF":9.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146097694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting the tumor immune microenvironment in chordoma: From mechanistic insights to therapeutic breakthroughs","authors":"Hao Zhang,&nbsp;Jingyu Xing,&nbsp;Zijie Yuan,&nbsp;Chenglong Zhao,&nbsp;Cheng Yang","doi":"10.1016/j.bbcan.2025.189520","DOIUrl":"10.1016/j.bbcan.2025.189520","url":null,"abstract":"<div><div>Chordoma is a rare, malignant bone tumor characterized by high local recurrence rates and resistance to conventional therapies. While immunotherapy has emerged as a promising avenue, its clinical efficacy is currently limited by a profoundly immunosuppressive tumor immune microenvironment (TIME). This review systematically elucidates the molecular and cellular mechanisms underpinning the distinct “immune-excluded” phenotype in chordoma. In this architecture, effector T cells are physically sequestered from tumor cells by dense stromal septa, which paradoxically function as hubs for myeloid-T cell interaction rather than simple physical barriers.</div><div>This immune-excluded architecture is orchestrated through multiple interconnected mechanisms. Cancer-associated fibroblasts (CAFs), particularly inflammatory and stress-related subpopulations, construct physical barriers via extracellular matrix remodeling while secreting chemokines (such as CXCL12) that spatially anchor T cells within the stroma. The transforming growth factor-beta (TGF-β) pathway reinforces this exclusion by suppressing cytotoxic T cell function and impeding tumor infiltration. Intrinsically, chordoma exhibits a low tumor mutational burden and specific genomic alterations—most notably the loss of CDKN2A/B and PBRM1. Furthermore, despite high chromosomal instability (CIN), co-occurring deletions of 9p and 10q silence the cGAS-STING pathway, thereby impairing antigen presentation and immune cell recruitment. The microenvironment is further dominated by M2-polarized tumor-associated macrophages and regulatory T cells, driving effector T cell exhaustion.</div><div>Clinical evidence indicates that immune checkpoint inhibitors and targeted vaccines yield limited efficacy as monotherapies, highlighting the immune-excluded phenotype and the scarcity of PD-L1 protein expression as primary obstacles. Future therapeutic breakthroughs will require rational combination strategies, including CAR-T cell therapies targeting novel antigens (e.g., B7-H3) and adoptive T-cell transfer, designed to dismantle stromal barriers and exploit systemic anti-tumor immunity.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1881 2","pages":"Article 189520"},"PeriodicalIF":9.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145835604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting store-operated Ca2+ entry as a novel strategy to overcome treatment resistance in melanoma","authors":"Daniela María Vega Gutiérrez ,&nbsp;Barbara A. Niemeyer ,&nbsp;Stephanie Kreis ,&nbsp;Sabrina Bréchard","doi":"10.1016/j.bbcan.2026.189548","DOIUrl":"10.1016/j.bbcan.2026.189548","url":null,"abstract":"<div><div>Cutaneous melanoma is the most aggressive form of skin cancer characterized by high metastatic potential and poor prognosis, particularly in advanced stages (stage III/IV). Despite more than a decade of significant advances in treatment including immunotherapies, oncolytic virus therapy, and adoptive cell therapy, clinical outcomes for patients with advanced melanoma remain unsatisfactory. This is primarily due to the tumor's intrinsic aggressiveness, intolerable side effects associated with treatments, and the rapid emergence of therapeutic resistance. Therefore, there is a critical need for novel therapeutic strategies that not only inhibit melanoma progression and metastasis but also overcome resistance mechanisms. After reviewing recent therapeutic developments, we highlight the potential of store-operated Ca²⁺ entry (SOCE) as a promising and thus far overlooked target to improve the efficacy of current melanoma therapies. We examine the role of SOCE in oncogenic signaling pathways driving melanoma progression and invasiveness. Emphasis is given to the key mechanisms regulated by SOCE that underlie therapeutic resistance. We further discuss how modulation of SOCE has the potential to reshape a tumor response to therapy by disrupting these mechanisms. Integrating SOCE modulation in combination with existing treatment paradigms holds significant potential for advancing more precise, durable, and patient-tailored interventions in advanced melanoma.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1881 2","pages":"Article 189548"},"PeriodicalIF":9.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146101206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging multi-omics biomarkers in glioblastoma: Integrative insights from genomics to metabolomics","authors":"Ganesh S. Kakde ,&nbsp;Tikam Chand Dakal ,&nbsp;Pawan Kumar Maurya","doi":"10.1016/j.bbcan.2026.189540","DOIUrl":"10.1016/j.bbcan.2026.189540","url":null,"abstract":"<div><div>Glioblastoma (GBM) is the most malignant form of primary brain tumor in adults, described by profound molecular heterogeneity, rapid progression, and limited therapeutic response. Despite advances in chemotherapy (TMZ), radiotherapy, and surgery, patient outcomes remain poor, with a median survival of 12–15 months. Traditional single-omics studies have identified critical biomarkers such as IDH mutations, MGMT promoter methylation, and EGFR alterations; however, these provide only partial insight into the disease's complexity. Recent integrative multi-omics approaches encompassing genomics, transcriptomics, epigenomics, proteomics, metabolomics, and non-coding RNAs have transformed the landscape of biomarker discovery in GBM. Genomic profiling has revealed recurrent mutations and subtype-specific aberrations, while transcriptomic analyses refine molecular classification and uncover alternative splicing and fusion events. Epigenomic markers, particularly MGMT methylation and G-CIMP status, are now central to prognosis and therapy stratification. Proteomic and metabolomic studies highlight dysregulated pathways, metabolic vulnerabilities, and non-invasive biomarkers in cerebrospinal fluid and plasma. Integrating multi-omics data not only improves diagnostic and prognostic accuracy but also unveils therapeutic targets, offering opportunities for precision oncology. Furthermore, liquid biopsy and single-cell/spatial omics enhance real-time monitoring of disease progression and treatment response, addressing challenges posed by intratumoral heterogeneity. This review synthesizes recent advances in GBM biomarker research across multiple omics layers, emphasizing their complementary roles in unravelling tumor biology, guiding personalized treatment, and shaping future therapeutic strategies.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1881 2","pages":"Article 189540"},"PeriodicalIF":9.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146036704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Harnessing microRNAs in lung cancer: The future of diagnosis and precision therapy","authors":"Daniela Alexandre ,&nbsp;Pedro V. Baptista ,&nbsp;Carla Cruz","doi":"10.1016/j.bbcan.2026.189535","DOIUrl":"10.1016/j.bbcan.2026.189535","url":null,"abstract":"<div><div>Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related death, driven by late diagnosis and therapeutic resistance. microRNAs (miRs) regulate post-transcriptional networks across cancer hallmarks and are unusually stable in biofluids, positioning them as powerful, minimally invasive biomarkers and therapeutic targets. This review summarizes current knowledge on miR biogenesis, regulation, and function in NSCLC; critically evaluates circulating and compartment-specific biomarkers (plasma/serum, sputum, and peripheral blood mononuclear cells (PBMCs); and appraises translational advances in oncomiR inhibition and tumor-suppressor restoration using modern delivery systems. We also analyze methodological progress, highlight persistent pre-analytical and normalization challenges, and outline practical routes toward regulatory-grade standardization. Convergent evidence indicates that circulating and exosomal miR panels can improve early detection and malignant-nodule triage, particularly when integrated with imaging and proteomic markers, and provide independent prognostic and treatment-monitoring value, often anticipating radiographic response or resistance. Despite strong pre-clinical efficacy, the clinical translation of miR mimics and inhibitors has been limited by delivery barriers and immunotoxicity, constraining progress into late-phase development. Unstandardized workflows and incomplete attribution of tumor-derived signals remain key barriers to clinical adoption. Overall, miRs hold strong potential to advance precision oncology in NSCLC through real-time disease monitoring and pathway-level targeting. Progress will likely depend on multimodal integration with circulating tumor DNA (ctDNA), proteomics, and imaging, alongside optimized delivery strategies, improved immunosafety, and rigorous multicenter validation to enable translation into routine care.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1881 2","pages":"Article 189535"},"PeriodicalIF":9.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146044347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}