Biochimica et biophysica acta. Reviews on cancer最新文献

{"title":"Calcium and cancer metastasis: Discoveries from zebrafish xenografts","authors":"Ghazala Rahman,&nbsp;Anamika Bhargava","doi":"10.1016/j.bbcan.2025.189446","DOIUrl":"10.1016/j.bbcan.2025.189446","url":null,"abstract":"<div><div>Cancer metastasis remains the leading cause of cancer-related deaths, highlighting the urgent need for therapies targeting metastatic processes. Dysregulated calcium (Ca²⁺) signaling is increasingly linked to metastasis and offers a promising, underexplored therapeutic target. The zebrafish xenograft model has emerged as a powerful tool for studying cancer due to its optical transparency, genetic similarity to humans, and rapid development. This review outlines how zebrafish xenografts have been employed to investigate Ca²⁺ signaling in cancer progression, revealing roles for ORAI1 in nasopharyngeal carcinoma, TRPM8 in prostate cancer, VDAC1 and TMBIM6 in breast cancer, and TRPV1 in gastric cancer. These studies highlight the zebrafish xenograft model's advantages in visualization, cost, and throughput over traditional systems. Despite its promise, the zebrafish xenograft model remains underutilized in Ca²⁺-related metastasis research. Future work using transgenic lines like tg-EGFP:flk1 and tg-GCaMP, CRISPR knockouts, morpholinos or optogenetic approaches could unlock deeper insights and guide novel metastasis-targeting therapies.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 5","pages":"Article 189446"},"PeriodicalIF":9.7,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145034745","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 CD39-CD73-adenosine axis: Master regulator of immune evasion and therapeutic target in pancreatic ductal adenocarcinoma","authors":"Xiaolong Liu ,&nbsp;Qingzhu Ding ,&nbsp;Han Zhang ,&nbsp;Xiang Zhang ,&nbsp;Qiangda Chen ,&nbsp;Shangeng Weng","doi":"10.1016/j.bbcan.2025.189443","DOIUrl":"10.1016/j.bbcan.2025.189443","url":null,"abstract":"<div><div>Pancreatic ductal adenocarcinoma (PDAC) exhibits persistent resistance to immunotherapy, with a 5-year survival rate around 10 %. The CD39-CD73-adenosine axis emerges as a critical mediator of immune evasion in PDAC, generating pathologically elevated adenosine concentrations that systematically suppress anti-tumor immunity. This purinergic pathway operates through sequential ATP hydrolysis by CD39 and CD73 ectonucleotidases, producing adenosine that engages four G-protein-coupled receptors (A1, A2A, A2B, A3) to orchestrate comprehensive immunosuppression. A2A and A2B receptors mediate the predominant immunosuppressive effects through cAMP-PKA signaling, inhibiting CD8+ T cell and NK cell cytotoxicity while enhancing regulatory T cells, myeloid-derived suppressor cells, and M2-like tumor-associated macrophages. Cancer-associated fibroblasts and tumor cells contribute to adenosine production and respond to its signaling, establishing self-reinforcing immunosuppressive networks. Current therapeutic strategies demonstrate promising early clinical results, with multiple CD73 inhibitors, CD39 antagonists, and adenosine receptor antagonists under evaluation in PDAC trials. However, critical challenges remain: CD73's non-enzymatic functions promote chemoresistance independently of adenosine production, explaining why enzymatic inhibitors fail to enhance chemotherapy sensitivity. The spatial adenosine gradient within tumors, receptor-specific paradoxical effects, and compensatory resistance mechanisms through AMP accumulation further complicate therapeutic targeting. Multi-targeted approaches combining adenosine pathway inhibition with checkpoint blockade, chemotherapy, and stromal modulation show enhanced efficacy. Future directions include developing predictive biomarker panels, optimizing combination sequences, and designing inhibitors targeting both enzymatic and structural functions of purinergic enzymes. Understanding these complex interactions provides the foundation for transforming the adenosine pathway from an immunosuppressive barrier into a therapeutic opportunity in PDAC.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 5","pages":"Article 189443"},"PeriodicalIF":9.7,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145034802","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 role of protein glycosylation in colorectal cancer: From molecular pathways to clinical applications","authors":"Tiangui Wu ,&nbsp;Jianguo Gu ,&nbsp;Yuhan Sun ,&nbsp;Pengfei Ye","doi":"10.1016/j.bbcan.2025.189438","DOIUrl":"10.1016/j.bbcan.2025.189438","url":null,"abstract":"<div><div>Glycosylation, a pivotal post-translational modification, critically influences colorectal cancer (CRC) progression via dysregulated <em>N</em>- and <em>O</em>-linked pathways, characterized by oligomannose, fucosylation, hypersialylation, truncated <em>O</em>-glycans (Tn, sialyl-Tn), branched <em>N</em>-glycans, and Lewis antigens. These alterations promote tumor aggressiveness, immune evasion, and metastasis through glycoprotein remodeling (e.g., mucins, integrins) and dysregulating glycosyltransferases (such as Fut2, ST6GAL1). Clinically, tumor-associated glycans offer diagnostic potential, with glycomic profiling enhancing early detection. Glycosylation further orchestrates the CRC microenvironment by modulating interactions among tumor cells, microbiota, and immune components. This review focuses exclusively on protein-centric glycosylation and highlights current studies on the roles of glycosylation in CRC, encompassing molecular mechanisms, diagnostic biomarkers, and emerging therapeutic strategies targeting glycosylation enzymes or glycan epitopes. Understanding glycan dysregulation provides new perspectives for biomarker development and targeted interventions in precision oncology.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 5","pages":"Article 189438"},"PeriodicalIF":9.7,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145034806","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":"Heparanase as a therapeutic target for mitigating cancer progression","authors":"Yogesh Kumar ,&nbsp;Lokesh Gambhir ,&nbsp;Gaurav Sharma ,&nbsp;Asha Sharma ,&nbsp;Neha Kapoor","doi":"10.1016/j.bbcan.2025.189441","DOIUrl":"10.1016/j.bbcan.2025.189441","url":null,"abstract":"<div><div>Cancer has been one of the primary causes of mortality for the last three decades across the globe, with contemporary treatment modalities often falling short due to limitations viz. drug resistance, toxicity, and the inability to target molecular mechanisms of tumor progression. Among various intracellular mediators implicated in cancer progression, heparanase, a heparan sulfate degrading enzyme, has been pivotal by facilitating tumor invasion, angiogenesis, and metastasis. Inhibiting the activity of heparanase is a promising therapeutic approach that can potentially curtail tumor growth and metastasis, offering a novel strategy to curb cancer progression. The present review underpins the discovery, structural features, and functional roles of heparanase, with a focus on its differential expression in normal and cancer cell state. Further, the review provides an insight in several classes of heparanase inhibitors including nucleic acid-based inhibitors, polysulfated saccharides, vaccines, miRNA, monoclonal antibodies, natural compounds and small molecule inhibitors along with their mechanism of action and potential benefits in cancer therapy. Recent advancements in heparanase inhibitor development, especially those agents that have moved into clinical trials and received patents is also highlighted thereby underscoring their therapeutic potential and commercial viability. The present review emphasizes over the potential of heparanase as a therapeutic agent and provides an extensive summary of actual endeavors to develop effective inhibitors that may substantiate the forthcoming landscape of cancer treatment.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 5","pages":"Article 189441"},"PeriodicalIF":9.7,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145034743","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":"Innate immune cells in oral squamous cell carcinoma: Characteristics and therapeutic potential","authors":"Yinjie Jiang ,&nbsp;Jingyi Cheng ,&nbsp;Jianjun Wu ,&nbsp;Ousheng Liu ,&nbsp;Xin Bin","doi":"10.1016/j.bbcan.2025.189444","DOIUrl":"10.1016/j.bbcan.2025.189444","url":null,"abstract":"<div><div>Innate immune cells play an important role in the immune system and are mainly responsible for the rapid response to foreign pathogens, damaged tissues, or abnormal cells. However, their immunophenotype in oral squamous cell carcinoma (OSCC) is altered due to the influence of various components within the tumour microenvironment, including tumour cells, cancer associated fibroblasts, and the extracellular matrix. This immunophenotypic shift results in the suppression of anti-tumour-related immune functions and active participation in further remodelling of the tumour microenvironment. These remodelled innate immune cells are further involved in crosstalk with other components within the tumour microenvironment (TME), resulting in tumour immune reprogramming via multiple pathways in a positive feedback manner. This process facilitates tumour development, metastasis, and immune evasion, while impeding the efficacy of tumour immunotherapy. Consequently, disrupting the positive feedback loop through which innate immune cells are remodelled and actively reprogrammed within the tumour microenvironment may improve therapeutic outcomes and prognosis of patients with OSCC. Therefore, this article aimed to provide an overview of the reprogramming patterns of innate immune cells within the TME of OSCC, and the major pathways through which these cells participate in the regulation of TME. Additionally, this review summarises and discusses therapeutic approaches targeting innate immune cells in OSCC, and provides novel insights for the development of treatment strategies targeting the functions of innate immune cells in OSCC.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 5","pages":"Article 189444"},"PeriodicalIF":9.7,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145024870","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 role of clonal hematopoiesis of indeterminate potential in non-hematological malignancies of various origins","authors":"Bo Zheng ,&nbsp;Jie He ,&nbsp;Wanqian Hu ,&nbsp;Qiqi Cao ,&nbsp;Rong Li","doi":"10.1016/j.bbcan.2025.189442","DOIUrl":"10.1016/j.bbcan.2025.189442","url":null,"abstract":"<div><div>Clonal hematopoiesis of indeterminate potential (CHIP) bridges hematopoietic clonality and solid tumorigenesis, unveiling a systemic dimension of somatic mutagenesis in cancer biology. Generally, population studies demonstrate CHIP carriers face elevated risks of cancer and poorer survival outcomes. This review consolidates current knowledge on the role of CHIP as potential biomarkers in the prediction/early detection/prognosis evaluation of various non-hematological cancers. We provide an overview of recent studies demonstrating the clinical consequences of CHIP including mosaic chromosomal alterations (mCA) across multiple cancer types. Furthermore, we collected the lab studies focusing on the impact of CHIP genes gain/loss in myeloid/lymphoid cells in non-hematological cancers, highlighting the underlying molecular mechanism and therapeutic targets. This review underscores the clinical impact of CHIP in non-hematological cancers, also the complicated cancer-regulating role of CHIP, highlighting targeting CHIP-associated pathways or integrating CHIP status into clinical decision-making could revolutionize precision oncology.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 5","pages":"Article 189442"},"PeriodicalIF":9.7,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145018604","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 evolving landscape of antibody-drug conjugates in small cell lung cancer: From research progress to clinical application","authors":"Haoyu Wang ,&nbsp;Chenyue Zhang ,&nbsp;Haiyong Wang","doi":"10.1016/j.bbcan.2025.189445","DOIUrl":"10.1016/j.bbcan.2025.189445","url":null,"abstract":"<div><div>Antibody-drug conjugates (ADCs), one of the emerging developing classes of antitumor drugs, have transformed the therapeutic paradigm in oncology. It stands out due to its properties of boasting the strength of both chemotherapy and targeted therapy. In small cell lung cancer (SCLC), ADC has also demonstrated its potential and appealing effect. Clinical trials of ADCs in SCLC are currently in full swing. While ADC has brought some encouraging results so far, several obstacles have been encountered, such as drug resistance, drug toxicities and the difficulty in the selection of patients benefiting from ADCs. Thus, a deepened and comprehensive understanding of the fundamental researches, as well as summarization of ADC development in SCLC might offer us some enlightenment and solutions to these tricky issues. Therefore, in the present review, we elaborate on the structure and mechanism of ADC, clinical trials conducted in SCLC. Additionally, we also outline the obstacles and propose future directions of ADC in SCLC, highlighting its in-depth research and prospective application in SCLC.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 6","pages":"Article 189445"},"PeriodicalIF":9.7,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145016949","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":"Unveiling anaphylatoxins: Pioneering cancer therapies through complement system insights","authors":"Jiamu Li ,&nbsp;Xinqiao Li ,&nbsp;Jinpeng Hu ,&nbsp;Zinan You ,&nbsp;Zhitao Jing","doi":"10.1016/j.bbcan.2025.189436","DOIUrl":"10.1016/j.bbcan.2025.189436","url":null,"abstract":"<div><div>The complement system, a cornerstone of innate immunity, plays pivotal roles in both defense and pathology, particularly through its anaphylatoxins, C3a and C5a. These small peptides, generated during complement activation, not only mediate pro-inflammatory responses but also contribute to the progression of various cancers by modulating the tumor microenvironment (TME). Anaphylatoxins influence tumor cell proliferation, epithelial-mesenchymal transition, angiogenesis, immune suppression, and therapy resistance via key signaling pathways such as PI3K/AKT, MEK/ERK, and p38 MAPK. This review summarizes recent findings on the roles of C3a and C5a in different tumor types, including glioma, lung cancer, melanoma, breast cancer, and hematological malignancies, highlighting their potential as biomarkers and therapeutic targets. Additionally, we discuss the development of anaphylatoxin inhibitors, their clinical applications, and the synergistic effects of combining these inhibitors with immune checkpoint blockade therapies. A deeper understanding of anaphylatoxin-mediated mechanisms may provide novel strategies for cancer diagnosis, prognosis, and treatment, paving the way for targeted and combination therapies to overcome tumor progression and immune evasion.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 5","pages":"Article 189436"},"PeriodicalIF":9.7,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145008619","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":"Cancer stem cells in focus: Deciphering the dynamic functional landscape of stemness in cancer","authors":"Gabriel C. Nwokolo ,&nbsp;Trivadi Sundaram Ganesan ,&nbsp;Klaus Pors ,&nbsp;Robert A. Falconer ,&nbsp;Sneha Smarakan","doi":"10.1016/j.bbcan.2025.189440","DOIUrl":"10.1016/j.bbcan.2025.189440","url":null,"abstract":"<div><div>Cancer stem cells (CSCs) are central to tumour initiation, progression, and relapse, yet their dynamic and adaptive nature hampers therapeutic targeting. Once viewed as a fixed subpopulation, CSCs are now recognised as a fluid functional state that tumour cells can enter or exit, driven by intrinsic programs, epigenetic reprogramming, and microenvironmental cues. This plasticity complicates identification due to inconsistent marker expression and enables resistance, dormancy, and metastasis. Epigenetic regulators and miRNAs further reinforce stemness under therapeutic stress, keeping the CSC concept contested. Despite promising preclinical efforts, clinical translation of CSC-targeted therapies remains limited by inadequate models and incomplete understanding of CSC-state transitions. This review examines CSC heterogeneity and regulation, while highlighting limitations of current markers and models. We propose that not all committed cancer cells sustain tumour growth; rather, a subset with stem-competent potential may dedifferentiate into CSCs. Finally, we propose future directions to define actionable vulnerabilities and improve CSC-directed therapies.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 5","pages":"Article 189440"},"PeriodicalIF":9.7,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145006929","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":"Colorectal cancer chemoprevention: Exploring the path from molecular mechanisms to available drugs","authors":"Devon M. Ivy,&nbsp;Rosa Bordone,&nbsp;Laura Di Magno,&nbsp;Sonia Coni,&nbsp;Gianluca Canettieri","doi":"10.1016/j.bbcan.2025.189439","DOIUrl":"10.1016/j.bbcan.2025.189439","url":null,"abstract":"<div><div>Colorectal cancer (CRC) remains a significant global health challenge despite advances in screening and diagnostic modalities that have contributed to reduced incidence and mortality. A substantial proportion of cases, however, continue to be diagnosed at advanced stages. Chemoprevention – the use of natural or synthetic substances to prevent cancer initiation or recurrence - has emerged as a promising strategy, particularly for individuals at elevated risk. While several agents have shown clinical efficacy, the underlying mechanisms driving their protective effects are not yet fully understood. In this Review, we provide a comprehensive overview of the molecular pathogenesis of CRC and highlight key druggable targets relevant to chemoprevention, including inflammation, polyamine metabolism, mitochondrial function, epigenetic regulation, and promising new avenues targeting aspects such as the tumor microenvironment and the gut microbiota. We provide a significant contribution to the field by intersecting the established clinical and preclinical results to the growing understanding of chemopreventative mechanism of action, identifying potential for the stratification of patient risks and benefits among their molecular roles and side effects. Finally, based on the improved molecular understanding of CRC tumorigenesis, we propose potential new avenues of colorectal chemoprevention.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 5","pages":"Article 189439"},"PeriodicalIF":9.7,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144996137","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}