Biochimica et biophysica acta. Reviews on cancer最新文献

{"title":"Animal models in preclinical evaluation of CAR-T cell therapy: Advantages and limitations","authors":"Lasse von Bornemann Fløe ,&nbsp;Maya Graham Pedersen ,&nbsp;Bjarne K. Møller","doi":"10.1016/j.bbcan.2025.189455","DOIUrl":"10.1016/j.bbcan.2025.189455","url":null,"abstract":"<div><div>Chimeric Antigen Receptor T (CAR-T) cell therapy is a promising new treatment category. Animal models have played a pivotal role in advancing CAR-T cell therapy. However, no animal model fully replicates human physiology, leading to unsuccessful translation from preclinical models to clinical trials. Understanding the advantages and limitations of various animal model choices requires insight into CAR-T cell mechanisms and their interactions across experimental contexts.</div><div>CAR-T cell immunobiology differs between animal models and humans. This disparity is reflected in the limited translational capacity of pharmacological parameters and the absence of key immunological interactions in animal models compared to those seen in human trials. Additionally, the antigen specificity of the CAR introduces translational limitations. Differences in antigen density and expression among different cellular populations across species are critical factors to consider when interpreting preclinical results. Xenoreactivity, stemming from the original T-cell receptor repertoire, also limits experimental duration and timing in mouse models.</div><div>Modeling human cancer in animal models requires many considerations. Cancer heterogeneity varies significantly between patient-derived xenografts and cell-line-based xenografts. Syngeneic models more accurately mimic interactions between CAR-T cells and other immune components, while xenograft models better reflect human tumor antigen expression. Beyond CAR-T-specific challenges, issues with standardization and replication in animal studies affect the reliability of the results. Furthermore, ethical guidelines should guide experimental planning to minimize animal use and prioritize humane treatment.</div><div>This review explores the strengths and limitations of animal models preclinical CAR-T cell therapy research, while offering critical considerations for interpreting results and designing experiments.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 6","pages":"Article 189455"},"PeriodicalIF":9.7,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145103139","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":"Intricate role of DRP1 and associated mitochondrial fission signaling in carcinogenesis and cancer progression","authors":"Soumya Ranjan Mishra ,&nbsp;Priyadarshini Mishra ,&nbsp;Prakash Kumar Senapati ,&nbsp;Kewal Kumar Mahapatra ,&nbsp;Sujit Kumar Bhutia","doi":"10.1016/j.bbcan.2025.189453","DOIUrl":"10.1016/j.bbcan.2025.189453","url":null,"abstract":"<div><div>The process of mitochondrial fission is a major determinant of mitochondrial homeostasis. DRP1 is the chief architect of the mitochondrial fission process, and the DRP1 recruitment to the mitochondrial outer membrane is necessary for the mitochondrial division. DRP1 contributes to cancer progression by promoting cell proliferation, enhancing resistance to therapy, inhibiting apoptosis, suppressing immune responses, and sustaining cancer stem cell heterogeneity and self-renewal. Moreover, DRP1 drives metabolic reprogramming to support enhanced energy production and biosynthesis required for tumor growth and survival. In addition, DRP1-mediated mitochondrial fission also favours NLRP3 inflammasome activation within the tumor microenvironment, which regulates cancer progression. Interestingly, elevated levels of DRP1 expression have been identified as a significant prognostic marker, correlating with poor survival outcomes across multiple cancer types. Many DRP1 inhibitors have been developed for cancer treatment, but more specific and selective agents are needed to improve efficacy and reduce off-target effects. A comprehensive understanding of DRP1's role in cancer cells is essential for developing DRP1 inhibitors, which hold promise as novel anticancer therapies and may enhance the effectiveness of conventional treatments.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 6","pages":"Article 189453"},"PeriodicalIF":9.7,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145088253","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":"Functional dichotomy of autophagy signaling in tumor microenvironment driving hallmarks in oral cancer","authors":"Sushmita Patra ,&nbsp;Bishnu Prasad Behera ,&nbsp;Birija Sankar Patro ,&nbsp;Sujit Kumar Bhutia","doi":"10.1016/j.bbcan.2025.189451","DOIUrl":"10.1016/j.bbcan.2025.189451","url":null,"abstract":"<div><div>As a cytoprotective mechanism, autophagy recycles damaged proteins and organelles via the lysosomal degradation pathway in response to diverse stress conditions. However, its role in tumor microenvironment, including oral cancer, is still a point of contention. Although excessive autophagy is associated with cell death, many studies have revealed elevated autophagy levels in advanced stages of oral cancer, providing a suitable niche for growth and proliferation. On the contrary, disruption of basal level autophagy also contributes to oral cancer development at the early stage due to increased oxidative stress and accumulation of genetic mutations. This atypical dependence of oral cancer cells on autophagy is associated with cellular features, stage, and requirements. The present study highlights the involvement of key autophagy-related proteins in oral cancer progression and explores their interaction with oncogenic signaling pathways that drive proliferation, chemoresistance, metabolic reprogramming, and metastasis. Furthermore, increased autophagy in cancer-associated fibroblasts, immune cells, and macrophages within the tumor microenvironment contributes to fibroblast activation, cytokine secretion, and immune suppression, enhancing tumor plasticity. Notably, crosstalk between autophagy and the NLRP3 inflammasome has emerged as a significant factor in promoting oral cancer progression and metastasis. Finally, accumulating evidence supports the therapeutic potential of autophagy modulators, which enhance apoptosis and suppress tumor growth, suggesting that targeting autophagy could offer promising treatment strategies for resistant oral cancers.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 6","pages":"Article 189451"},"PeriodicalIF":9.7,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145066699","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":"Mechanisms of tumor aggressiveness driven by ablation-induced niche remodeling","authors":"Shuyue Gao ,&nbsp;Ting Luo ,&nbsp;Fangying Fan ,&nbsp;Ping Liang ,&nbsp;Jie Yu","doi":"10.1016/j.bbcan.2025.189449","DOIUrl":"10.1016/j.bbcan.2025.189449","url":null,"abstract":"<div><div>Tumor niche represents a dynamic, functionally specialized microenvironment defined by reciprocal interactions between tumor cells and their surrounding stroma. However, emerging evidence suggests that ablation-induced niche remodeling may promote tumor aggressiveness, counteracting therapeutic benefits. This review summarizes current insights into the role of ablation-induced niche remodeling in tumor progression. We begin with a bibliometric analysis to illustrate research trends and identify the hotspots. We then explore the underlying biological mechanisms of niche remodeling post-ablation, with a focus on three key aspects: resistance to cell death, immune cell reprogramming toward immunosuppression, and enhanced tumor invasiveness and migration. These insights may inform future research directions and support the development of more effective clinical strategies.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 6","pages":"Article 189449"},"PeriodicalIF":9.7,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058770","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":"Unraveling the role of mitochondrial dynamics in cancer stem cells: Molecular basis and therapeutic implications","authors":"Gaia Giannitti,&nbsp;Sara Marchesi,&nbsp;Riccardo Garavaglia,&nbsp;Ivan Preosto,&nbsp;Fabrizio Fontana","doi":"10.1016/j.bbcan.2025.189450","DOIUrl":"10.1016/j.bbcan.2025.189450","url":null,"abstract":"<div><div>Many tumors consist of heterogeneous cell populations derived from a minority of cancer stem cells (CSCs), which possess distinct metabolic profiles that contribute to resistance against conventional anticancer therapy and increase the risk of tumor relapse. These unique CSC phenotypes are largely supported by altered mitochondrial function and turnover, regulated through continuous cycles of mitochondrial biogenesis, fission, fusion, and mitophagy. Consequently, understanding mitochondrial regulatory mechanisms in CSCs could reveal novel targets for cancer therapy. This article explores how mitochondrial dynamics contribute to CSC metabolic adaptation and drug resistance, alongside recent advances in the development of mitochondria-targeted drugs and their therapeutic usage.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 6","pages":"Article 189450"},"PeriodicalIF":9.7,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145056341","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":"Hydrogen sulfide and carbon monoxide as possible regulators of YY1 and RKIP: Novel insights into gastrointestinal cancers pathogenesis","authors":"Edyta Korbut ,&nbsp;Małgorzata Lasota ,&nbsp;Daniel Jankowski ,&nbsp;Łukasz Szeleszczuk ,&nbsp;Marcin Magierowski","doi":"10.1016/j.bbcan.2025.189448","DOIUrl":"10.1016/j.bbcan.2025.189448","url":null,"abstract":"<div><div>Gastrointestinal (GI) cancers remain among the leading causes of cancer-related mortality, with challenges in early detection, therapeutic resistance, and poor prognosis. Two key molecular players, Yin Yang 1 (YY1) and Raf kinase inhibitor protein (RKIP), have emerged as important regulators of cancer progression and treatment response. This review highlights their individual and interactive roles across various GI malignancies, including gastric, colorectal, pancreatic, and liver cancers. Evidence indicates an antagonistic relationship, where YY1 promotes tumor growth and epithelial-mesenchymal transition (EMT), while RKIP counters these effects by suppressing oncogenic signaling pathways. On the other hand, endogenous gaseous transmitter, nitric oxide (NO) has been clearly shown to influence the YY1-RKIP axis. NO directly inhibits YY1 via S-nitrosylation and promotes RKIP expression, reinforcing pro-apoptotic and anti-metastatic pathways. Although some scientific evidence exists, the role of another gaseous mediator, hydrogen sulfide (H₂S), as a modulator of YY1 or RKIP remains poorly characterized. Its regulatory influence, especially via interaction with NO signaling, suggests a complex, context-dependent role. H₂S/sulfides-mediated posttranslational modification of proteins – persulfidation - has been shown recently to be functionally important but not in the context of YY1 or RKIP activity. Moreover, carbon monoxide (CO) that interacts with metalloproteins has been completely overlooked as possible regulator of YY1/RKIP-dependent cancer biology. Therefore, we indicate here the possible interplay between H₂S and CO with YY1/RKIP that may provide new further scientific direction in this field, based on aggressive GI tumors.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 5","pages":"Article 189448"},"PeriodicalIF":9.7,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145042700","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":"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}