Mitochondria continuously alternate between fragmented and fused states, a process known as mitochondrial dynamics, which plays a pivotal role in essential cellular functions, including metabolism, apoptosis, reactive oxygen species production, and signal transduction. Disruptions in this dynamic equilibrium, frequently observed in aggressive cancers, can promote malignant transformation and tumor progression. A growing body of evidence indicates that dysregulated mitochondrial dynamics contribute to resistance against both conventional and targeted anticancer therapies. In this review, we explore the regulatory mechanisms governing mitochondrial dynamics, with a focus on the genetic and epigenetic modulation of key drivers such as DRP1, MFN1/2 and OPA1. We also discuss how altered mitochondrial dynamics converge into diverse mechanisms of drug resistance in cancer. Overall, these insights underscore aberrant mitochondrial dynamics as a potential biomarker of therapeutic resistance, and position mitochondrial dynamics–related GTPases, particularly DRP1 and Mitofusins, as exploitable targets for novel treatments in advanced solid and hematologic malignancies.
{"title":"Dysregulated mitochondrial dynamics in cancer: Unlocking new strategies to combat drug resistance","authors":"Teresa Rossi , Roberta Torcasio , Ludovica Ganino , Ilenia Valentino , Christian Boni , Massimo Gentile , Antonino Neri , Nicola Amodio , Mariaelena Pistoni","doi":"10.1016/j.bbcan.2025.189510","DOIUrl":"10.1016/j.bbcan.2025.189510","url":null,"abstract":"<div><div>Mitochondria continuously alternate between fragmented and fused states, a process known as mitochondrial dynamics, which plays a pivotal role in essential cellular functions, including metabolism, apoptosis, reactive oxygen species production, and signal transduction. Disruptions in this dynamic equilibrium, frequently observed in aggressive cancers, can promote malignant transformation and tumor progression. A growing body of evidence indicates that dysregulated mitochondrial dynamics contribute to resistance against both conventional and targeted anticancer therapies. In this review, we explore the regulatory mechanisms governing mitochondrial dynamics, with a focus on the genetic and epigenetic modulation of key drivers such as DRP1, MFN1/2 and OPA1. We also discuss how altered mitochondrial dynamics converge into diverse mechanisms of drug resistance in cancer. Overall, these insights underscore aberrant mitochondrial dynamics as a potential biomarker of therapeutic resistance, and position mitochondrial dynamics–related GTPases, particularly DRP1 and Mitofusins, as exploitable targets for novel treatments in advanced solid and hematologic malignancies.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1881 1","pages":"Article 189510"},"PeriodicalIF":9.7,"publicationDate":"2025-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145710459","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}
Metabolic reprogramming is a hallmark of cancer, enabling tumor cells to fulfill increased bioenergetic and biosynthetic demands for survival and proliferation. These adaptations arise directly from oncogenic mutations or indirectly via adaptive responses to nutrient scarcity. In addition to supporting survival and biomass production, these metabolic shifts are closely associated with changes in gene expression, cellular differentiation, and the tumor microenvironment, thereby contributing to tumorigenesis and progression. Importantly, the recognition of metabolic dysregulation as a hallmark of malignancy revealed novel avenues for therapeutic intervention, as disrupting these pathways may impair energy generation and biosynthetic processes essential for tumor proliferation. In this review, we integrate data indicating that the transcription factor Yin yang 1 (YY1) is a central regulator of oncogenic metabolic reprogramming. Yin yang 2 (YY2) is a paralog of YY1 and performs distinct role in metabolism and redox regulation. Mechanistically, YY1 enhances aerobic glycolysis by diverting glycolytic flux toward lactate production. Furthermore, it modulates hepatic lipid homeostasis via direct transcriptional control of lipogenic enzymes and crosstalk with nutrient-sensing signaling cascades. Additionally, YY1 rewires amino acid metabolism to fuel tumorigenesis by supplying macromolecules and enabling epigenetic remodeling. Collectively, these findings highlight the equilibrium between YY1 and its paralog YY2 in sustaining redox homeostasis and tumor progression while positioning YY1 as a metabolic checkpoint that dynamically regulates these processes. Understanding these pathways will support development of YY1-directed inhibitors and combinatorial therapies to modulate metabolic reprogramming in cancer.
{"title":"YY1: Master regulator of metabolic reprogramming in cancer","authors":"Rimsha Akram , Rendy Hosea , Fuqiang Zhao , Andrzej Górecki , Małgorzata Figiel , Shourong Wu , Vivi Kasim","doi":"10.1016/j.bbcan.2025.189505","DOIUrl":"10.1016/j.bbcan.2025.189505","url":null,"abstract":"<div><div>Metabolic reprogramming is a hallmark of cancer, enabling tumor cells to fulfill increased bioenergetic and biosynthetic demands for survival and proliferation. These adaptations arise directly from oncogenic mutations or indirectly via adaptive responses to nutrient scarcity. In addition to supporting survival and biomass production, these metabolic shifts are closely associated with changes in gene expression, cellular differentiation, and the tumor microenvironment, thereby contributing to tumorigenesis and progression. Importantly, the recognition of metabolic dysregulation as a hallmark of malignancy revealed novel avenues for therapeutic intervention, as disrupting these pathways may impair energy generation and biosynthetic processes essential for tumor proliferation. In this review, we integrate data indicating that the transcription factor Yin yang 1 (YY1) is a central regulator of oncogenic metabolic reprogramming. Yin yang 2 (YY2) is a paralog of YY1 and performs distinct role in metabolism and redox regulation. Mechanistically, YY1 enhances aerobic glycolysis by diverting glycolytic flux toward lactate production. Furthermore, it modulates hepatic lipid homeostasis via direct transcriptional control of lipogenic enzymes and crosstalk with nutrient-sensing signaling cascades. Additionally, YY1 rewires amino acid metabolism to fuel tumorigenesis by supplying macromolecules and enabling epigenetic remodeling. Collectively, these findings highlight the equilibrium between YY1 and its paralog YY2 in sustaining redox homeostasis and tumor progression while positioning YY1 as a metabolic checkpoint that dynamically regulates these processes. Understanding these pathways will support development of YY1-directed inhibitors and combinatorial therapies to modulate metabolic reprogramming in cancer.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1881 1","pages":"Article 189505"},"PeriodicalIF":9.7,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145703261","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}
Pub Date : 2025-12-05DOI: 10.1016/j.bbcan.2025.189507
Yuting Sun , Weijia Kong , Xiaoyu Zhu , Xuelei Chu, Xinmiao Wang, Guanghui Zhu, Xue He, Jie Li
Non-small cell lung cancer (NSCLC) is associated with a high incidence and mortality rate, imposing a significant economic burden worldwide. The development of standardized diagnostic and targeted therapeutic approaches is essential. Protein post-translational modifications (PTMs) play a critical role in regulating biological functions during both physiological and pathological states, as they reversibly and dynamically adjust protein activity in response to changes in internal and external conditions. Various types of PTMs, including ubiquitination, phosphorylation, glycosylation, Small Ubiquitin-like Modifier (SUMO)ylation, acetylation, palmitoylation, and lactylation, have been shown to correlate significantly with the onset, progression, metastasis, treatment, and drug resistance of NSCLC. These modifications are involved in the initiation and progression of NSCLC and are linked to patient survival outcomes. Additionally, different therapeutic modalities, such as chemotherapy, radiation therapy, and immunotherapy, can influence treatment efficacy by altering PTMs. However, the challenge of drug resistance significantly undermines therapeutic effectiveness and patient outcomes. This review emphasizes the importance of PTMs in drug resistance and highlights their potential to inform more precise treatment strategies for NSCLC, ultimately contributing to a reduction in disability-adjusted life years, which is of considerable practical importance.
{"title":"Novel insights in the diagnosis and treatment of non-small cell lung cancer: Post-translational modification of proteins","authors":"Yuting Sun , Weijia Kong , Xiaoyu Zhu , Xuelei Chu, Xinmiao Wang, Guanghui Zhu, Xue He, Jie Li","doi":"10.1016/j.bbcan.2025.189507","DOIUrl":"10.1016/j.bbcan.2025.189507","url":null,"abstract":"<div><div>Non-small cell lung cancer (NSCLC) is associated with a high incidence and mortality rate, imposing a significant economic burden worldwide. The development of standardized diagnostic and targeted therapeutic approaches is essential. Protein post-translational modifications (PTMs) play a critical role in regulating biological functions during both physiological and pathological states, as they reversibly and dynamically adjust protein activity in response to changes in internal and external conditions. Various types of PTMs, including ubiquitination, phosphorylation, glycosylation, Small Ubiquitin-like Modifier (SUMO)ylation, acetylation, palmitoylation, and lactylation, have been shown to correlate significantly with the onset, progression, metastasis, treatment, and drug resistance of NSCLC. These modifications are involved in the initiation and progression of NSCLC and are linked to patient survival outcomes. Additionally, different therapeutic modalities, such as chemotherapy, radiation therapy, and immunotherapy, can influence treatment efficacy by altering PTMs. However, the challenge of drug resistance significantly undermines therapeutic effectiveness and patient outcomes. This review emphasizes the importance of PTMs in drug resistance and highlights their potential to inform more precise treatment strategies for NSCLC, ultimately contributing to a reduction in disability-adjusted life years, which is of considerable practical importance.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1881 1","pages":"Article 189507"},"PeriodicalIF":9.7,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145703231","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}
Pub Date : 2025-12-04DOI: 10.1016/j.bbcan.2025.189506
Yaohua Hu , Zhite Zhao , Yifan Ma , Xinglin He , Changhong Shi
Prostate cancer (PCa) is a highly prevalent malignant tumor in men, often progressing to castration-resistant prostate cancer (CRPC) and metastasis or neuroendocrine differentiation, leading to treatment failure. Its high heterogeneity and immunosuppressive tumor microenvironment (TME) are major challenges in treatment, characterized by low immunogenicity and a complex “tumor-stroma-immune” interaction network. Monoamine oxidase (MAO), a mitochondrial enzyme that degrades monoamine neurotransmitters and dietary amines via MAOA and MAOB isoforms. Studies have shown that MAOA and MAOB exhibit differential expression patterns in cancer cells, stromal cells, and immune cells, and may function cooperatively to promote PCa progression. This review clarifies how MAO influence PCa progression by regulating the “tumor-stroma-immune” interaction network, elucidate the impact of MAO on CD8+ T-cell infiltration and tumor-associated macrophages (TAMs) polarization in the TME, and proposes that precision targeting of MAO offers a stage- and cell-type-spanning strategy to surmount immunotherapy resistance in PCa. It provides a theoretical basis for developing intervention strategies based on MAO inhibitor to achieve effective immunotherapy for PCa.
{"title":"Targeting MAO offers a novel immunotherapeutic strategy for prostate cancer by modulating the “tumor-stroma-immune” interaction network","authors":"Yaohua Hu , Zhite Zhao , Yifan Ma , Xinglin He , Changhong Shi","doi":"10.1016/j.bbcan.2025.189506","DOIUrl":"10.1016/j.bbcan.2025.189506","url":null,"abstract":"<div><div>Prostate cancer (PCa) is a highly prevalent malignant tumor in men, often progressing to castration-resistant prostate cancer (CRPC) and metastasis or neuroendocrine differentiation, leading to treatment failure. Its high heterogeneity and immunosuppressive tumor microenvironment (TME) are major challenges in treatment, characterized by low immunogenicity and a complex “tumor-stroma-immune” interaction network. Monoamine oxidase (MAO), a mitochondrial enzyme that degrades monoamine neurotransmitters and dietary amines via MAOA and MAOB isoforms. Studies have shown that MAOA and MAOB exhibit differential expression patterns in cancer cells, stromal cells, and immune cells, and may function cooperatively to promote PCa progression. This review clarifies how MAO influence PCa progression by regulating the “tumor-stroma-immune” interaction network, elucidate the impact of MAO on CD8<sup>+</sup> T-cell infiltration and tumor-associated macrophages (TAMs) polarization in the TME, and proposes that precision targeting of MAO offers a stage- and cell-type-spanning strategy to surmount immunotherapy resistance in PCa. It provides a theoretical basis for developing intervention strategies based on MAO inhibitor to achieve effective immunotherapy for PCa.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1881 1","pages":"Article 189506"},"PeriodicalIF":9.7,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145696155","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}
Pub Date : 2025-12-02DOI: 10.1016/j.bbcan.2025.189503
Carme Solé-Blanch , Sofia España , Alba de la Puente-Noel , Oskar Marin-Béjar , José Luis Manzano , Anna Martinez-Cardús
BRAF mutations are key oncogenic drivers across multiple cancers, yet their therapeutic exploitation varies markedly by tumor type. In melanoma, the combination of BRAF and MEK inhibitors has revolutionized treatment, yielding unprecedented clinical benefits. However, both intrinsic and acquired resistance mechanisms continue to limit long-term efficacy. In contrast, BRAF-targeted therapies in colorectal cancer (CRC) have shown limited success, even when combined with EGFR inhibitors to counteract compensatory survival pathways. Despite these differences, resistance ultimately emerges in both malignancies, driven by partially overlapping mechanisms that remain incompletely understood in CRC. This review dissects the “yin-yang” of BRAF as a therapeutic vulnerability in these two malignancies, we underscore the critical importance of tumor-specific context in precision oncology. Understanding the divergent responses to BRAF inhibition across cancer types is essential to refine current approaches and guide the development of more effective, personalized treatment strategies.
{"title":"Same mutation, different fates: The Yin-Yang of BRAF-driven therapeutic responses in melanoma and colorectal cancer","authors":"Carme Solé-Blanch , Sofia España , Alba de la Puente-Noel , Oskar Marin-Béjar , José Luis Manzano , Anna Martinez-Cardús","doi":"10.1016/j.bbcan.2025.189503","DOIUrl":"10.1016/j.bbcan.2025.189503","url":null,"abstract":"<div><div>BRAF mutations are key oncogenic drivers across multiple cancers, yet their therapeutic exploitation varies markedly by tumor type. In melanoma, the combination of BRAF and MEK inhibitors has revolutionized treatment, yielding unprecedented clinical benefits. However, both intrinsic and acquired resistance mechanisms continue to limit long-term efficacy. In contrast, BRAF-targeted therapies in colorectal cancer (CRC) have shown limited success, even when combined with EGFR inhibitors to counteract compensatory survival pathways. Despite these differences, resistance ultimately emerges in both malignancies, driven by partially overlapping mechanisms that remain incompletely understood in CRC. This review dissects the “yin-yang” of BRAF as a therapeutic vulnerability in these two malignancies, we underscore the critical importance of tumor-specific context in precision oncology. Understanding the divergent responses to BRAF inhibition across cancer types is essential to refine current approaches and guide the development of more effective, personalized treatment strategies.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1881 1","pages":"Article 189503"},"PeriodicalIF":9.7,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145679505","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}
The tumor microenvironment is a dynamic, heterogeneous cellular ecosystem that includes cancer cells, cancer-associated fibroblasts (CAFs), endothelial cells, and immune cells. Immortalized cancer cell lines specific to a particular cancer type have been extensively used to investigate the anticancer effects and functional aspects of novel drugs. However, cancer cell lines do not accurately mimic the complex multicellular nature of organs. Since species-specific differences in mouse models of human cancer impact the interpretation of therapeutic efficacy, efforts have been made to reduce and replace the use of animals in the drug development process. It is now acknowledged that existing tumor models may not adequately simulate the tumor microenvironment. This has led to an increasing need for complex tumor models that can accurately represent the tumor immune microenvironment (TIME). The Organ-on-Chip (OoC) device has features that enable high-throughput screening and repeatable drug testing procedures by accurately simulating the tumor microenvironment (TME). Furthermore, although animal models remain vital for systemic analysis, the interpretation of therapeutic efficacy is often hindered by species-specific differences in immune and physiological responses. This limitation has created a critical conceptual gap in preclinical research. We acknowledge the pressing need for complex tumor models that can accurately simulate the tumor immune microenvironment (TIME).
The immune system plays two key roles in cancer: fighting tumors and promoting the development of carcinogenesis. Recent advances have been made in understanding how the immune system contributes to cancer progression and the development of immune cell treatments for improved prognosis. In vivo and in vitro models have been created to investigate therapy resistance and the function of the tumor immune microenvironment (TIME) in anticancer therapy. This review provides a critical and balanced evaluation of the various in vitro (organoids, organ-on-chip, bioprinting) and in vivo (PDX, Humanized Mice) models utilized to study the TIME. We move beyond descriptive summaries to offer a functional comparison of these platforms, specifically delineating their utility in overcoming the clinical challenges of therapy resistance mechanisms and translational immunotherapy evaluations. This comparative approach demonstrates how advanced models, such as organ-on-chip (OoC), which enable dynamic control of the microenvironment and integration of multiple organs, can complement and refine the drug development process.
{"title":"Application of in vitro and in vivo cancer models to study the impact of the tumor immune microenvironment on anticancer therapy","authors":"Rajat Gupta , Raghu Radhakrishnan , Shama Prasada Kabekkodu , Sanjiban Chakrabarty","doi":"10.1016/j.bbcan.2025.189504","DOIUrl":"10.1016/j.bbcan.2025.189504","url":null,"abstract":"<div><div>The tumor microenvironment is a dynamic, heterogeneous cellular ecosystem that includes cancer cells, cancer-associated fibroblasts (CAFs), endothelial cells, and immune cells. Immortalized cancer cell lines specific to a particular cancer type have been extensively used to investigate the anticancer effects and functional aspects of novel drugs. However, cancer cell lines do not accurately mimic the complex multicellular nature of organs. Since species-specific differences in mouse models of human cancer impact the interpretation of therapeutic efficacy, efforts have been made to reduce and replace the use of animals in the drug development process. It is now acknowledged that existing tumor models may not adequately simulate the tumor microenvironment. This has led to an increasing need for complex tumor models that can accurately represent the tumor immune microenvironment (TIME). The Organ-on-Chip (OoC) device has features that enable high-throughput screening and repeatable drug testing procedures by accurately simulating the tumor microenvironment (TME). Furthermore, although animal models remain vital for systemic analysis, the interpretation of therapeutic efficacy is often hindered by species-specific differences in immune and physiological responses. This limitation has created a critical conceptual gap in preclinical research. We acknowledge the pressing need for complex tumor models that can accurately simulate the tumor immune microenvironment (TIME).</div><div>The immune system plays two key roles in cancer: fighting tumors and promoting the development of carcinogenesis. Recent advances have been made in understanding how the immune system contributes to cancer progression and the development of immune cell treatments for improved prognosis. In vivo and in vitro models have been created to investigate therapy resistance and the function of the tumor immune microenvironment (TIME) in anticancer therapy. This review provides a critical and balanced evaluation of the various in vitro (organoids, organ-on-chip, bioprinting) and in vivo (PDX, Humanized Mice) models utilized to study the TIME. We move beyond descriptive summaries to offer a functional comparison of these platforms, specifically delineating their utility in overcoming the clinical challenges of therapy resistance mechanisms and translational immunotherapy evaluations. This comparative approach demonstrates how advanced models, such as organ-on-chip (OoC), which enable dynamic control of the microenvironment and integration of multiple organs, can complement and refine the drug development process.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1881 1","pages":"Article 189504"},"PeriodicalIF":9.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145665668","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}
Pub Date : 2025-11-01DOI: 10.1016/j.bbcan.2025.189489
Senxu Lu , Junxiu Liu , Shixin Chen , Binghao Li , Zhaoming Ye
N6-methyladenosine (m6A) modification, a dynamic and reversible post-transcriptional RNA alteration, plays a critical role in the precise regulation of gene expression and is fundamentally implicated in the interplay between tumor cells and the immune system. This review focuses on the regulatory mechanisms of m6A methylation in tumor immunology. We examine how m6A modifications within tumor cells reprogram the tumor immune microenvironment by modulating immune checkpoints, canonical signaling pathways, and cytokine secretion, as well as directly regulating immune-related genes. Crucially, we also dissect how m6A modification within immune cells shapes the immune microenvironment. Furthermore, we propose novel therapeutic strategies combining m6A targeting with immunotherapy. Collectively, this review provides novel insights into the role of m6A methylation in tumor immunology and paves the way for future research directions.
{"title":"M6A methylation in tumor immune microenvironment: Multidimensional mechanism and targeted therapy strategies","authors":"Senxu Lu , Junxiu Liu , Shixin Chen , Binghao Li , Zhaoming Ye","doi":"10.1016/j.bbcan.2025.189489","DOIUrl":"10.1016/j.bbcan.2025.189489","url":null,"abstract":"<div><div>N6-methyladenosine (m<sup>6</sup>A) modification, a dynamic and reversible post-transcriptional RNA alteration, plays a critical role in the precise regulation of gene expression and is fundamentally implicated in the interplay between tumor cells and the immune system. This review focuses on the regulatory mechanisms of m<sup>6</sup>A methylation in tumor immunology. We examine how m<sup>6</sup>A modifications within tumor cells reprogram the tumor immune microenvironment by modulating immune checkpoints, canonical signaling pathways, and cytokine secretion, as well as directly regulating immune-related genes. Crucially, we also dissect how m<sup>6</sup>A modification within immune cells shapes the immune microenvironment. Furthermore, we propose novel therapeutic strategies combining m<sup>6</sup>A targeting with immunotherapy. Collectively, this review provides novel insights into the role of m<sup>6</sup>A methylation in tumor immunology and paves the way for future research directions.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 6","pages":"Article 189489"},"PeriodicalIF":9.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145412478","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}
Pub Date : 2025-11-01DOI: 10.1016/j.bbcan.2025.189490
Pankaj Garg , Madhu Krishna , David Horne , Ravi Salgia , Sharad S. Singhal
Magnetochemistry is opening new frontiers in the targeted treatment of breast cancer (BC), offering a precise and innovative way to deliver therapies exactly where they're needed. Beyond drug delivery, magnetic nanoparticles (MNPs) can generate localized heat under alternating magnetic fields, initiating controlled hyperthermia that induces apoptotic cell death in tumor tissues. MNPs, particularly iron-oxide-based magnetite (Fe₃O₄) and maghemite (γ-Fe₂O₃), can be magnetically guided toward tumor sites and subsequently activated under alternating magnetic field (AMFs) (typically 100–500 kHz and 10–40 kA m−1) to generate therapeutic heat through Néel and Brownian relaxation losses. At the tumor, drugs can be released in a controlled manner in response to environmental cues such as pH changes, enzymes, or magnetic stimuli. By harnessing this dual role of MNPs, as targeted carriers and thermal effectors, researchers achieve spatially selective, minimally invasive treatment. Mechanistically, magnetically induced hyperthermia elevates local temperature to 42–46 °C, which triggers reactive oxygen species (ROS) generation, mitochondrial membrane depolarization, and caspase-3/9 activation—hallmarks of apoptosis in BC cells. This integrated approach not only concentrates drugs at the tumor but also sensitizes cancer cells to chemo- and radiotherapy, while minimizing systemic toxicity. Static or dynamic magnetic fields can be used to steer these particles, while their surfaces can be engineered through chemical bonding, physical encapsulation, or adsorption techniques. Moreover, combining magnetic targeting with antibody-based recognition improves specificity and therapeutic impact. While the promise of magnetochemistry in BC treatment is clear, ongoing research is essential to optimize these technologies and bring them fully into clinical practice.
磁化学为乳腺癌的靶向治疗开辟了新的领域，提供了一种精确和创新的方法，可以准确地在需要的地方提供治疗。除了药物递送，磁性纳米颗粒（MNPs）还可以在交变磁场下产生局部热量，启动可控热疗，诱导肿瘤组织中凋亡细胞死亡。MNPs，特别是氧化铁基磁铁矿（Fe₃O₄）和磁赤铁矿（γ-Fe₂O₃），可以被磁引导到肿瘤部位，随后在交变磁场（AMFs）（通常为100-500 kHz和10-40 kA m−1）下被激活，通过nsamel和布朗松弛损失产生治疗性热。在肿瘤中，药物可以根据环境因素（如pH值变化、酶或磁刺激）以可控的方式释放。通过利用MNPs作为靶向载体和热效应剂的双重作用，研究人员实现了空间选择性、微创治疗。从机制上说，磁诱导热疗将局部温度升高到42-46℃，从而触发活性氧（ROS）的产生、线粒体膜去极化和caspase-3/9的激活——这是BC细胞凋亡的标志。这种综合方法不仅可以将药物集中在肿瘤上，还可以使癌细胞对化疗和放疗敏感，同时最大限度地减少全身毒性。可以使用静态或动态磁场来引导这些颗粒，而它们的表面可以通过化学键合，物理封装或吸附技术来设计。此外，将磁性靶向与基于抗体的识别相结合可以提高特异性和治疗效果。虽然磁化学在BC治疗中的前景是明确的，但正在进行的研究对于优化这些技术并将其充分应用于临床实践至关重要。
{"title":"Hyperthermia-induced apoptosis: The role of magnetic nanoparticles in targeted delivery for breast cancer treatment","authors":"Pankaj Garg , Madhu Krishna , David Horne , Ravi Salgia , Sharad S. Singhal","doi":"10.1016/j.bbcan.2025.189490","DOIUrl":"10.1016/j.bbcan.2025.189490","url":null,"abstract":"<div><div>Magnetochemistry is opening new frontiers in the targeted treatment of breast cancer (BC), offering a precise and innovative way to deliver therapies exactly where they're needed. Beyond drug delivery, magnetic nanoparticles (MNPs) can generate localized heat under alternating magnetic fields, initiating controlled hyperthermia that induces apoptotic cell death in tumor tissues. MNPs, particularly iron-oxide-based magnetite (Fe₃O₄) and maghemite (γ-Fe₂O₃), can be magnetically guided toward tumor sites and subsequently activated under alternating magnetic field (AMFs) (typically 100–500 kHz and 10–40 kA m<sup>−1</sup>) to generate therapeutic heat through Néel and Brownian relaxation losses. At the tumor, drugs can be released in a controlled manner in response to environmental cues such as pH changes, enzymes, or magnetic stimuli. By harnessing this dual role of MNPs, as targeted carriers and thermal effectors, researchers achieve spatially selective, minimally invasive treatment. Mechanistically, magnetically induced hyperthermia elevates local temperature to 42–46 °C, which triggers reactive oxygen species (ROS) generation, mitochondrial membrane depolarization, and caspase-3/9 activation—hallmarks of apoptosis in BC cells. This integrated approach not only concentrates drugs at the tumor but also sensitizes cancer cells to chemo- and radiotherapy, while minimizing systemic toxicity. Static or dynamic magnetic fields can be used to steer these particles, while their surfaces can be engineered through chemical bonding, physical encapsulation, or adsorption techniques. Moreover, combining magnetic targeting with antibody-based recognition improves specificity and therapeutic impact. While the promise of magnetochemistry in BC treatment is clear, ongoing research is essential to optimize these technologies and bring them fully into clinical practice.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 6","pages":"Article 189490"},"PeriodicalIF":9.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145412480","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}
Pub Date : 2025-11-01DOI: 10.1016/j.bbcan.2025.189483
Shaopeng Chang , Longhui Li , Yumiao Liu , Gan Huang , Shu-Ting Pan
Tongue squamous cell carcinoma (TSCC), the most prevalent oral malignancy, demonstrates rising global incidence and mortality rates, while current therapies exhibit limited efficacy in advanced-stage disease. The tumor microenvironment (TME) constitutes an intricate ecosystem of immune cells, fibroblasts, and extracellular matrix (ECM), which collectively regulate TSCC progression, immune evasion, and therapeutic resistance. Tumor immunotherapies targeting TME have been increasingly validated in clinical trials, and despite the ability to capture relevant immune features in TME, challenges such as low individual response rates and immunotherapy resistance still exist in the clinic. In this review, we address the mechanisms of TSCC-associated immune cells as well as extracellular-related components in TME, summarize the effects of each component of TME on tumor immune response, and look forward to the application of tumor immunotherapy and immune-combination therapies to improve the efficacy of individualized precision medicine for TSCC.
{"title":"Advances in tumor micro-environment and immunotherapy of squamous cell carcinoma of the tongue","authors":"Shaopeng Chang , Longhui Li , Yumiao Liu , Gan Huang , Shu-Ting Pan","doi":"10.1016/j.bbcan.2025.189483","DOIUrl":"10.1016/j.bbcan.2025.189483","url":null,"abstract":"<div><div>Tongue squamous cell carcinoma (TSCC), the most prevalent oral malignancy, demonstrates rising global incidence and mortality rates, while current therapies exhibit limited efficacy in advanced-stage disease. The tumor microenvironment (TME) constitutes an intricate ecosystem of immune cells, fibroblasts, and extracellular matrix (ECM), which collectively regulate TSCC progression, immune evasion, and therapeutic resistance. Tumor immunotherapies targeting TME have been increasingly validated in clinical trials, and despite the ability to capture relevant immune features in TME, challenges such as low individual response rates and immunotherapy resistance still exist in the clinic. In this review, we address the mechanisms of TSCC-associated immune cells as well as extracellular-related components in TME, summarize the effects of each component of TME on tumor immune response, and look forward to the application of tumor immunotherapy and immune-combination therapies to improve the efficacy of individualized precision medicine for TSCC.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 6","pages":"Article 189483"},"PeriodicalIF":9.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145370577","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}
Pub Date : 2025-11-01DOI: 10.1016/j.bbcan.2025.189495
Sophia N. Baptista , Alessandra V.S. Faria , Carmen V. Ferreira-Halder
Melanoma, an aggressive skin cancer, poses significant global health challenges due to its increasing incidence and high metastatic potential. While traditionally focused on genetic mutations, recent research highlights the critical role of cellular organelle dysfunction and intricate inter-organelle communication in both keratinocytes and melanocytes during melanoma pathogenesis. This systematic review explores how alterations within key organelles, including mitochondria, endoplasmic reticulum (ER), Golgi apparatus, lysosomes, peroxisomes, and lamellar bodies. reprogram cellular behavior and contribute to disease progression. We detail how mitochondrial dysfunction and elevated reactive oxygen species (ROS) levels in keratinocytes can prime the microenvironment for melanocyte transformation. Lysosomes and peroxisomes, vital for degradation, lipid metabolism, and redox balance, when compromised, impair cellular differentiation and oxidative stress management, fostering a pro-tumorigenic state. The ER and ribosomes, crucial for protein synthesis and quality control, are frequently impacted by environmental stressors like UV radiation, leading to adaptive or detrimental cellular responses. Furthermore, the proper function of lamellar bodies, essential for skin barrier integrity, is intrinsically linked to Golgi and lysosomal health, with disruptions influencing melanoma dissemination. Understanding the complex interplay and dysregulation of these organelles offers a multifaceted perspective on melanoma, moving beyond isolated cellular events to reveal systemic imbalances. This review underscores the potential for developing novel strategies that target specific organelle pathways, aiming to restore cellular homeostasis and effectively combat tumor progression.
{"title":"Keratinocyte organelle reprogramming as a key player in melanocyte biology in health and disease","authors":"Sophia N. Baptista , Alessandra V.S. Faria , Carmen V. Ferreira-Halder","doi":"10.1016/j.bbcan.2025.189495","DOIUrl":"10.1016/j.bbcan.2025.189495","url":null,"abstract":"<div><div>Melanoma, an aggressive skin cancer, poses significant global health challenges due to its increasing incidence and high metastatic potential. While traditionally focused on genetic mutations, recent research highlights the critical role of cellular organelle dysfunction and intricate inter-organelle communication in both keratinocytes and melanocytes during melanoma pathogenesis. This systematic review explores how alterations within key organelles, including mitochondria, endoplasmic reticulum (ER), Golgi apparatus, lysosomes, peroxisomes, and lamellar bodies. reprogram cellular behavior and contribute to disease progression. We detail how mitochondrial dysfunction and elevated reactive oxygen species (ROS) levels in keratinocytes can prime the microenvironment for melanocyte transformation. Lysosomes and peroxisomes, vital for degradation, lipid metabolism, and redox balance, when compromised, impair cellular differentiation and oxidative stress management, fostering a pro-tumorigenic state. The ER and ribosomes, crucial for protein synthesis and quality control, are frequently impacted by environmental stressors like UV radiation, leading to adaptive or detrimental cellular responses. Furthermore, the proper function of lamellar bodies, essential for skin barrier integrity, is intrinsically linked to Golgi and lysosomal health, with disruptions influencing melanoma dissemination. Understanding the complex interplay and dysregulation of these organelles offers a multifaceted perspective on melanoma, moving beyond isolated cellular events to reveal systemic imbalances. This review underscores the potential for developing novel strategies that target specific organelle pathways, aiming to restore cellular homeostasis and effectively combat tumor progression.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 6","pages":"Article 189495"},"PeriodicalIF":9.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145515232","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}
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