Biochimica et biophysica acta. Reviews on cancer最新文献

{"title":"Oncogenic mutation-driven metabolism-immunity regulatory axis: Potential prospects for thyroid cancer precision therapy","authors":"Tingting Zhang ,&nbsp;Hengtong Han ,&nbsp;Tianying Zhang ,&nbsp;Yating Zhang ,&nbsp;Libin Ma ,&nbsp;Ze Yang ,&nbsp;Yong-xun Zhao","doi":"10.1016/j.bbcan.2025.189459","DOIUrl":"10.1016/j.bbcan.2025.189459","url":null,"abstract":"<div><div>Oncogenes enhance cancer development, and their specific activating mutations exemplify the mechanisms that initiate and mediate thyroid cancer (TC) progression. Research has predominantly focused on how oncogenes promote the development of different TC subtypes by influencing the downstream signaling pathways. Targeted therapies show significant efficacy; however, they often induce drug resistance through feedback activation or compensatory signaling bypasses. Recent evidence indicates that thyroid oncogenes initiate and mediate TC progression, and contribute to drug resistance in distinct TC subtypes through induced metabolic reprogramming and immune microenvironment remodeling. Hence, we propose the concept “Oncogene-Metabolism-Immunity axis.” We discussed the molecular mechanisms by which oncogene-driven metabolic reprogramming and tumor immune microenvironment Remodeling (TIME), and their mutual interactions, induce TC progression, drug resistance, and immune evasion. Finally, we systematically evaluated and summarized potential strategies targeting key oncogenes, metabolic catalysts, immune checkpoints (ICs), and combination therapies to enhance the efficacy of targeted treatments for TC and overcome drug resistance.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 6","pages":"Article 189459"},"PeriodicalIF":9.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145156212","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":"Opposing roles of YY1 and RKIP in cancer progression and therapy resistance","authors":"Christos Rigopoulos ,&nbsp;Stavroula Baritaki ,&nbsp;Ilias Georgakopoulos-Soares ,&nbsp;Benjamin Bonavida ,&nbsp;Apostolos Zaravinos","doi":"10.1016/j.bbcan.2025.189488","DOIUrl":"10.1016/j.bbcan.2025.189488","url":null,"abstract":"<div><div>Yin Yang 1 (YY1) and Raf kinase inhibitory protein (RKIP, encoded by PEBP1) are multifunctional regulators with antagonistic roles in tumor biology. YY1 functions as a context-dependent transcription factor and chromatin organizer, integrating enhancer–promoter looping and super-enhancer activity to drive oncogenic transcriptional programs, immune evasion, and therapy resistance. By contrast, RKIP restrains the NF-κB, MAPK and STAT3 pathways, suppressing epithelial–mesenchymal transition, metastasis, and chemoresistance. Recent pan-cancer transcriptomic analyses highlight a recurrent pattern of YY1 upregulation and RKIP downregulation, with inverse correlations in several tumor types (e.g., lung, colorectal and kidney). Clinically, high YY1 expression is associated with poor survival and diminished responses to chemotherapy, TRAIL, and immune checkpoint blockade, whereas high RKIP predicts improved outcomes and restored therapeutic sensitivity. YY1 and RKIP also modulate key immune compartments: YY1 promotes Treg expansion, myeloid-derived suppressor cell (MDSC) accumulation, tumor-associated macrophage (TAM) polarization, and impaired antigen presentation, while RKIP counteracts these processes and enhances cytotoxic T and NK cell activity. Therapeutically, YY1 can be targeted through BET/p300 inhibitors, emerging PROTAC degraders, and RNA- or CRISPR-based approaches; RKIP restoration is under investigation via kinase and pathway modulators. Together, YY1 and RKIP constitute a regulatory axis with prognostic and predictive value, offering potential for biomarker-driven patient stratification and novel therapeutic strategies in precision oncology.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 6","pages":"Article 189488"},"PeriodicalIF":9.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145454487","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":"2025-11-01","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":"The role of fatty acid oxidation in metabolic crosstalk between tumor cells and associated factors in the microenvironment","authors":"Suman Pakhira ,&nbsp;Subhadip Kundu ,&nbsp;Sib Sankar Roy","doi":"10.1016/j.bbcan.2025.189447","DOIUrl":"10.1016/j.bbcan.2025.189447","url":null,"abstract":"<div><div>Metabolic reprogramming is a defining characteristic of cancer cells as they undergo multistage development. Cancer cells dynamically adjust their metabolism to aid their survival and to retain their malignant traits within the adverse tumour microenvironment (TME). Fatty acid oxidation (FAO) is a major source of cellular bioenergy, making it a key player in driving cancer cell growth. Over the past few years, an accumulating body of literature has shed light on the role of dysregulated FAO in cancer progression. Besides energy production, FAO also plays a protective role by mitigating lipotoxicity-induced cell death and preventing oxidative stress through NADPH production. Moreover, FAO is intricately linked with numerous critical signaling pathways, substantiating its importance as a pivotal metabolic adaptation in cancer cells. In the TME, various intrinsic and extrinsic factors continuously modulate the behaviour of cancer cells, including their metabolic attributes, such as the activation of FAO. Additionally, alterations in FAO within non-cancerous stromal cells also play a critical role in orchestrating the tumor progression. Despite the emerging recognition of FAO's significance in cancer biology, the precise molecular mechanisms underlying its dysregulation within the TME remain poorly understood. Given the pivotal role of FAO in bioenergetically priming the tumor progression, its aberrant regulation has become a focal point of cancer research, offering potential avenues for novel therapeutic strategies. This review provides an overview of recent advances in understanding how different microenvironmental factors modulate FAO to influence tumor progression.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 6","pages":"Article 189447"},"PeriodicalIF":9.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145139696","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 multifaceted roles of ISG15 in cancer: Conjugated and free forms","authors":"Xinran Liu ,&nbsp;Qiujin Ma ,&nbsp;Zhao Jia ,&nbsp;Churong Zou ,&nbsp;Kun Huang","doi":"10.1016/j.bbcan.2025.189473","DOIUrl":"10.1016/j.bbcan.2025.189473","url":null,"abstract":"<div><div>Interferon-stimulated gene product 15 (ISG15) is a ubiquitin-like protein. It functions as a conjugated form by covalently modifying target proteins (ISGylation), or in a free form, both are involved in a broad variety of cellular processes. Increasing studies report the critical and complex roles of ISG15 in cancer progression and development. Herein, based on its conjugated or free form, we summarize ISG15-related oncogenic characteristics, such as cancer stemness, invasion and metastasis, anti-apoptosis and cancer drug resistance, and review ISG15-regulated oncogenic pathways, highlighting the molecular regulations of ISG15 in different cancers. This review aims to provide new insights into how ISG15 affects tumor pathogenesis, and propose potential cancer interventions targeting ISG15.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 6","pages":"Article 189473"},"PeriodicalIF":9.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145276851","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":"Sensory neuro-tumor crosstalk: Therapeutic opportunities and emerging frontiers in cancer neuroscience","authors":"Ying Wang ,&nbsp;Zhixin Ye ,&nbsp;Ye Yuan ,&nbsp;Chuanhao Wang ,&nbsp;Gang Chen ,&nbsp;Yonghui Zhang","doi":"10.1016/j.bbcan.2025.189464","DOIUrl":"10.1016/j.bbcan.2025.189464","url":null,"abstract":"<div><div>Emerging evidence in cancer neuroscience highlights the crucial role of sensory nerves in tumor progression, an aspect of cancer pathobiology previously overlooked. Mechanistically, tumor-associated sensory neurons establish a self-reinforcing oncogenic loop via secreted neurotrophic factors (e.g., NGF/BDNF), which directly promote cancer cell growth, spread, and treatment resistance through Trk activation. Concurrently, tumors rewire their local environment through dysregulated expression of axon guidance molecules, facilitating invasive growth. Importantly, nociceptive signaling activated during perineural invasion not only mediates cancer-related pain but also shapes an immunosuppressive microenvironment through neuropeptide-mediated changes in immune cell function. Current therapeutic strategies targeting tumor-associated nerves focus on: (1) Pharmacological blockade of nerve-tumor communication using small-molecule inhibitors (e.g., Trk inhibitor larotrectinib); (2) Bioelectronic modulation of neural activity via modalities such as transcutaneous electrical nerve stimulation. Notably, preclinical models reveal enhanced efficacy when combining neural modulation with immune checkpoint inhibitors. Technological breakthroughs, including single-cell analysis for precise nerve targeting and advanced drug delivery systems, are improving therapeutic precision. Consequently, understanding the complex interactions between nerves and tumors requires integrated approaches combining cancer biology, neuroimmunology, and systems neuroscience. This conceptual shift not only reshapes our understanding of cancer pathophysiology but also opens new avenues for precision therapies aligned with modern oncology.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 6","pages":"Article 189464"},"PeriodicalIF":9.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145187971","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":"Snake venom-derived peptides as anticancer candidates: Pioneering next-generation therapies","authors":"José R. Almeida ,&nbsp;Edgar.A. Pinos-Tamayo ,&nbsp;Bruno Mendes ,&nbsp;Alberto A. Robles-Loaiza ,&nbsp;Rony Abdi Syahputra ,&nbsp;Ana Gabriela Silva Oliveira ,&nbsp;Rosy Iara Maciel de A. Ribeiro","doi":"10.1016/j.bbcan.2025.189479","DOIUrl":"10.1016/j.bbcan.2025.189479","url":null,"abstract":"<div><div>Cancer treatment has come a long way, but not all cancers can be completely cured. The current therapeutic landscape has significantly reduced mortality rates; however, it remains associated with side effects, limited accessibility, financial burden, drug shortages, and emotional as well as mental health consequences for patients. Hence, despite significant advances, the development of novel therapies remains a focal point of research. In this review, we explore the current state of snake venom-inspired peptides as templates for the design of much-needed innovative anticancer agents. Initially, we examine conventional cancer treatments, their main challenges, and the niche filled by newly approved peptide-based therapies. Then, we present a high-level overview of the potential of snake venoms as broad-spectrum libraries of bioactive components and discuss a roadmap for mining these rich and complex mixtures to pioneer the next generation of cancer drugs, leading to the emergence of “oncovenomics”. Harnessing the potential of modern <em>in silico</em> approaches, we delve into the structure, biochemical parameters, and bioactivity of venom-inspired peptides. Our research identified more than 30 snake venom-derived peptides with micromolar lytic action against different cancer cells, including solid and liquid tumours. Transitioning from <em>in vitro</em> monolayer analyses to clinical settings remains an unfulfilled goal, with the majority of studies failing to progress to more advanced stages, including the preclinical phase involving <em>in vivo</em> experiments. Here, we also describe how artificial intelligence, and the integration of other cutting-edge technologies can provide an expandable framework for translating the high <em>in vitro</em> potential of venom-derived peptides into clinically useful therapies. Lastly, we examined the translational challenges and the strategies proposed to overcome them. In summary, snake venom-derived peptides are attractive scaffolds for drug discovery programs, demonstrating historical benefits. However, overcoming the existing barriers in their development requires further multidisciplinary efforts. On the horizon, advances in high-throughput research tools and peptide engineering strategies offer opportunities for introducing next-generation venom peptide-based therapeutics to address cancer in clinical practice.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 6","pages":"Article 189479"},"PeriodicalIF":9.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145331115","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 double-edged sword of IRF7: “Guardian” or “traitor” of tumors? From mechanistic contradictions to therapeutic revolution","authors":"Siyu Li ,&nbsp;Qiong Luo ,&nbsp;Jiali Hu ,&nbsp;Xiaobing Duan ,&nbsp;Guihai Zhang","doi":"10.1016/j.bbcan.2025.189501","DOIUrl":"10.1016/j.bbcan.2025.189501","url":null,"abstract":"<div><h3>Abstract</h3><div>Interferon Regulatory Factor 7 (IRF7) is emerging as a pivotal and paradoxical modulator in cancer biology, functioning both as a tumor suppressor and as a context-dependent oncogenic driver. This review not only covers classical features such as proliferative signaling, immune evasion, apoptosis resistance, and metastasis but also includes a dedicated discussion of the four emerging features added by Hanahan in 2022, namely, phenotypic plasticity, nonmutational epigenetic reprogramming, polymorphic microbiomes, and the dynamic balance of senescent cells. Mechanistically, IRF7 integrates transcriptional regulation, Posttranslational Modifications (PTMs), and microenvironmental cues to orchestrate diverse oncogenic processes, resulting in tissue-specific and spatiotemporal functional dichotomy. Furthermore, this review highlights the dualistic potential of IRF7 in therapeutic contexts—enhancing antitumor immunity and interferon signaling in some settings while contributing to immune suppression, therapeutic resistance, or tumor progression in others. Recent advances in drug development targeting IRF7, such as epigenetic modulation, kinase inhibition, and exosome-based delivery, suggest promising avenues for precision cancer therapy. However, the functional heterogeneity of IRF7 necessitates a nuanced therapeutic approach, emphasizing biomarker-guided stratification and spatiotemporal-specific interventions. Overall, IRF7 represents a key regulatory hub linked to immune, metabolic, and oncogenic pathways, with significant implications for future cancer diagnosis, prognosis, and treatment strategies.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 6","pages":"Article 189501"},"PeriodicalIF":9.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145596993","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":"Decoding the epigenetic landscape: ctDNA methylation as a game-changer in hepatocellular carcinoma management","authors":"Dexin Yang ,&nbsp;Yueru Yao ,&nbsp;Fenfang Gui ,&nbsp;Wuxuan Mei ,&nbsp;Changchun Zeng","doi":"10.1016/j.bbcan.2025.189497","DOIUrl":"10.1016/j.bbcan.2025.189497","url":null,"abstract":"<div><div>Hepatocellular carcinoma (HCC) constitutes a pressing global health issue, where conventional diagnostics like alpha-fetoprotein (AFP) and ultrasonography reveal limitations in early identification and prognostic reliability. Circulating tumor DNA (ctDNA) methylation has recently gained attention as an innovative “liquid biopsy” biomarker, offering epigenetic signatures and early disease signals through non-invasive detection. This review elucidates the mechanistic role of DNA methylation in HCC, highlighting its regulation of pivotal oncogenic cascades and its progression-dependent alterations. In addition, advanced detection techniques, such as restriction enzyme-based, enrichment-based, and bisulfite conversion-based approaches, were assessed in HCC. Moreover, the clinical applicability of ctDNA methylation in HCC was evaluated for early detection, prognostic assessment, and therapeutic surveillance. This review thoroughly outlines the current obstacles hindering the successful clinical translation of ongoing research. Furthermore, it outlines potential research directions to address these limitations and facilitate the rapid translation of findings into clinical practice. Ultimately, ctDNA methylation provides a significant advancement in deciphering the epigenetic profile of HCC, with potential benefits for precision oncology and patient outcomes.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 6","pages":"Article 189497"},"PeriodicalIF":9.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145544567","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 mechanics of anoikis resistance in cancer","authors":"Michela Corsini ,&nbsp;Mattia Domenichini ,&nbsp;Elisa Moreschi ,&nbsp;Stefania Mitola","doi":"10.1016/j.bbcan.2025.189498","DOIUrl":"10.1016/j.bbcan.2025.189498","url":null,"abstract":"<div><div>Metastatic cancer cells display a remarkable ability to resist the mechanical and biochemical challenges associated with detaching from the extracellular matrix and metastasize. A key adaptive mechanism in this process is resistance to anoikis. In this review, we explore the molecular and biophysical mechanisms that enable cancer cells to resist anoikis, with a focus on mechanotransduction. We discuss the roles of integrin signaling, the YAP/TAZ pathway, the mechanosensitive ion channels, and actomyosin contractility in sustaining survival under mechanical stress conditions. Furthermore, we highlight the emerging contribution of soluble mediators, particularly the myokine irisin, which acts as mechanical mimetics by activating survival pathways typically triggered by matrix engagement. We also examined how mechanical heterogeneity across tumor types and metastatic routes shapes context-specific adaptation strategies. By bridging physical forces and cell survival signaling, this review underscores mechanostransduction as fundamental driver of metastatic competence and a promising target for therapeutic intervention.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 6","pages":"Article 189498"},"PeriodicalIF":9.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145566661","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}