Biochimica et biophysica acta. Reviews on cancer最新文献_第6页

Posttranslational modifications in Helicobacter pylori-associated gastric pathogenesis: Bridging inflammation and carcinogenesis 幽门螺杆菌相关胃发病机制的翻译后修饰：桥接炎症和癌变。

IF 9.7 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Reviews on cancer

Pub Date : 2025-11-01 DOI: 10.1016/j.bbcan.2025.189492

Wei Li , Tong Liu , Tianhua Wu , Ting Cai , Fen Wang , Minglin Zhang

Helicobacter pylori (H. pylori), a Group I carcinogen that affects approximately half of the global population, is the primary aetiological agent of chronic gastritis, peptic ulcers, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue lymphoma. Its pathogenesis involves intricate interactions among bacterial virulence factors, host genetics, and environmental factors. We detail the critical role of diverse protein posttranslational modifications (PTMs) in mediating H. pylori-induced gastric mucosal damage and carcinogenesis. We describe how H. pylori exploits and dysregulates a broad spectrum of host and bacterial PTMs (encompassing acetylation, ubiquitination, S-nitrosylation, disulfide bond formation, citrullination, methylation, glycosylation, phosphorylation, SUMOylation, and ADP-ribosylation) to establish infection, evade immune responses, drive chronic inflammation, and promote malignant transformation. Collectively, these findings reveal a complex, multilayered PTM network that is central to H. pylori pathogenesis. Understanding these mechanisms provides crucial insights for the development of novel diagnostic biomarkers; methylation profiles; anti-citrullinate keratin 1 (Cit-K1) antibodies, maps of PTM dynamics; targeted therapeutic strategies, including PTM enzyme inhibitors, antivirulence agents such as H. pylori disulfide bond-forming protein A inhibitors, epigenetic modulators, glycoconjugate vaccines/adhesion blockers, and optimized drug delivery systems such as N-acetylcysteine liposomes. Furthermore, this knowledge supports improved risk stratification for managing persistent cancer risk even after eradication.

幽门螺杆菌（h.p ylori）是一类致癌物，影响全球大约一半的人口，是慢性胃炎、消化性溃疡、胃腺癌和胃粘膜相关淋巴组织淋巴瘤的主要病因。其发病机制涉及细菌毒力因素、宿主遗传和环境因素之间复杂的相互作用。我们详细介绍了多种蛋白质翻译后修饰（PTMs）在介导幽门螺杆菌诱导的胃粘膜损伤和癌变中的关键作用。我们描述了幽门螺杆菌如何利用和失调宿主和细菌的广谱PTMs（包括乙酰化、泛素化、s -亚硝基化、二硫键形成、瓜氨酸化、甲基化、糖基化、磷酸化、sumo酰化和adp核糖基化）来建立感染、逃避免疫反应、驱动慢性炎症和促进恶性转化。总的来说，这些发现揭示了一个复杂的、多层的PTM网络是幽门螺杆菌发病机制的核心。了解这些机制为开发新的诊断性生物标志物提供了重要的见解；甲基化配置文件;抗瓜氨酸角蛋白1 （Cit-K1）抗体，PTM动态图；靶向治疗策略，包括PTM酶抑制剂、抗毒剂（如幽门螺杆菌二硫键形成蛋白A抑制剂）、表观遗传调节剂、糖结合疫苗/粘附阻滞剂以及优化的药物递送系统（如n -乙酰半胱氨酸脂质体）。此外，这一知识支持改进风险分层，以管理即使在根除后持续的癌症风险。

{"title":"Posttranslational modifications in Helicobacter pylori-associated gastric pathogenesis: Bridging inflammation and carcinogenesis","authors":"Wei Li , Tong Liu , Tianhua Wu , Ting Cai , Fen Wang , Minglin Zhang","doi":"10.1016/j.bbcan.2025.189492","DOIUrl":"10.1016/j.bbcan.2025.189492","url":null,"abstract":"<div><div><em>Helicobacter pylori</em> (<em>H. pylori</em>), a Group I carcinogen that affects approximately half of the global population, is the primary aetiological agent of chronic gastritis, peptic ulcers, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue lymphoma. Its pathogenesis involves intricate interactions among bacterial virulence factors, host genetics, and environmental factors. We detail the critical role of diverse protein posttranslational modifications (PTMs) in mediating <em>H. pylori</em>-induced gastric mucosal damage and carcinogenesis. We describe how <em>H. pylori</em> exploits and dysregulates a broad spectrum of host and bacterial PTMs (encompassing acetylation, ubiquitination, S-nitrosylation, disulfide bond formation, citrullination, methylation, glycosylation, phosphorylation, SUMOylation, and ADP-ribosylation) to establish infection, evade immune responses, drive chronic inflammation, and promote malignant transformation. Collectively, these findings reveal a complex, multilayered PTM network that is central to <em>H. pylori</em> pathogenesis. Understanding these mechanisms provides crucial insights for the development of novel diagnostic biomarkers; methylation profiles; anti-citrullinate keratin 1 (Cit-K1) antibodies, maps of PTM dynamics; targeted therapeutic strategies, including PTM enzyme inhibitors, antivirulence agents such as <em>H. pylori</em> disulfide bond-forming protein A inhibitors, epigenetic modulators, glycoconjugate vaccines/adhesion blockers, and optimized drug delivery systems such as N-acetylcysteine liposomes. Furthermore, this knowledge supports improved risk stratification for managing persistent cancer risk even after eradication.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 6","pages":"Article 189492"},"PeriodicalIF":9.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145477374","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}

引用次数: 0

Rewiring PD-1/PD-L1 combination therapy via glyco-immune targeting of galectins: Toward clinical translation 通过糖免疫靶向凝集素重组PD-1/PD-L1联合治疗：走向临床转化

IF 9.7 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Reviews on cancer

Pub Date : 2025-11-01 DOI: 10.1016/j.bbcan.2025.189496

Xiangyu Huang, Si Zhang, Jiale Li, She Chen

Despite advances in PD-1/PD-L1 combination therapies, clinical benefits remain limited and toxicity is significant. Galectins, a family of β-galactoside-binding lectins, have emerged as mechanistically distinct, multimodal targets with the potential to address these limitations. By modulating glycan–protein networks in the tumor microenvironment, galectin inhibition alleviates T cell exclusion, immune exhaustion, immunosuppressive cell activation, and steric blockade of PD-(L)1 antibodies. Several galectin inhibitors (e.g., GR-MD-02, GB1211, LYT-200) are under clinical evaluation. Early trials showing encouraging efficacy-toxicity profiles and some combinations received FDA Fast Track designations. This review summarizes mechanistic and clinical advances and highlights their translational implications for galectin-targeted combination therapies.

尽管PD-1/PD-L1联合疗法取得了进展，但临床获益仍然有限，毒性也很明显。半乳糖凝集素是β-半乳糖苷结合凝集素的一个家族，已成为具有解决这些局限性潜力的机制独特的多模式靶点。通过调节肿瘤微环境中的聚糖-蛋白网络，半乳糖凝集素抑制可减轻T细胞排斥、免疫衰竭、免疫抑制细胞激活和PD-(L)1抗体的位阻。几种凝集素抑制剂（如GR-MD-02、GB1211、LYT-200）正在临床评估中。早期试验显示了令人鼓舞的药效-毒性特征和一些组合获得了FDA的快速通道指定。本文综述了半乳糖凝集素靶向联合治疗的机制和临床进展，并强调了它们的转化意义。

引用次数: 0

Corrigendum to “Snail1 as a key prognostic biomarker of cancer-associated fibroblasts in breast tumors” [Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, volume 1880 (2025) / 189316] “Snail1作为乳腺肿瘤中癌症相关成纤维细胞的关键预后生物标志物”的修正[biochemica et Biophysica Acta (BBA) - Reviews on Cancer, volume 1880(2025) / 189316]。

IF 9.7 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Reviews on cancer

Pub Date : 2025-11-01 DOI: 10.1016/j.bbcan.2025.189462

Raúl Peña, Josep Baulida

引用次数: 0

Opposing roles of YY1 and RKIP in cancer progression and therapy resistance YY1和RKIP在癌症进展和治疗耐药中的对立作用。

IF 9.7 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Reviews on cancer

Pub Date : 2025-11-01 DOI: 10.1016/j.bbcan.2025.189488

Christos Rigopoulos , Stavroula Baritaki , Ilias Georgakopoulos-Soares , Benjamin Bonavida , Apostolos Zaravinos

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.

由PEBP1编码的阴阳1 （YY1）和Raf激酶抑制蛋白（RKIP）是肿瘤生物学中具有拮抗作用的多功能调节因子。YY1作为一种环境依赖的转录因子和染色质组织者，整合增强子-启动子环和超级增强子活性，以驱动致癌转录程序、免疫逃避和治疗抵抗。相比之下，RKIP抑制NF-κB、MAPK和STAT3通路，抑制上皮-间质转化、转移和化疗耐药。最近的泛癌症转录组学分析强调了YY1上调和RKIP下调的复发模式，在几种肿瘤类型（如肺癌、结直肠癌和肾癌）中呈负相关。在临床上，YY1高表达与生存率差和化疗、TRAIL和免疫检查点阻断反应减弱有关，而高RKIP预测预后改善和治疗敏感性恢复。YY1和RKIP也调节关键的免疫区室：YY1促进Treg扩增、髓源性抑制细胞（MDSC）积累、肿瘤相关巨噬细胞（TAM）极化和抗原呈递受损，而RKIP抵消这些过程并增强细胞毒性T和NK细胞活性。在治疗上，YY1可以通过BET/p300抑制剂、新兴的PROTAC降解剂和基于RNA或crispr的方法靶向治疗；RKIP恢复正在通过激酶和通路调节剂进行研究。YY1和RKIP共同构成了一个具有预后和预测价值的调控轴，为精准肿瘤学的生物标志物驱动的患者分层和新的治疗策略提供了潜力。

{"title":"Opposing roles of YY1 and RKIP in cancer progression and therapy resistance","authors":"Christos Rigopoulos , Stavroula Baritaki , Ilias Georgakopoulos-Soares , Benjamin Bonavida , 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}

引用次数: 0

Nanoparticulate delivery and targeting of RNA to the brain 纳米颗粒递送和靶向RNA到大脑

IF 9.7 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Reviews on cancer

Pub Date : 2025-11-01 DOI: 10.1016/j.bbcan.2025.189480

Aditya Gupta , Raghu Ramanathan , Chittalsinh M. Raulji , Ram I. Mahato

The blood-brain barrier (BBB) presents a critical challenge in treating central nervous system (CNS) disorders, particularly aggressive brain cancers such as glioblastoma (GBM) and medulloblastoma (MB). RNA therapies exploit endogenous cellular machinery to modulate gene expression, targeting previously undruggable pathways. RNA and CRISPR gene therapies hold transformative potential for brain cancer but demand breakthroughs for enhanced drug transport across the BBB. While clinical achievements in non-CNS diseases validate their efficacy, interdisciplinary collaboration is essential to advance nanoparticles (NPs) engineering, immune evasion, and non-invasive delivery for CNS applications. NPs are indispensable for advancing RNA therapies in brain cancer, with lipid nanoparticles (LNPs) and viral vectors leading clinical translation. Innovations in targeting (e.g., GLUT1, RVG peptide, ApoE mimetic peptide) and non-invasive delivery (e.g., focused ultrasound) are critical to overcome the BBB limitations. This review highlights the different strategies that can be utilized to deliver RNA-based therapies to the brain and summarizes the recent clinical efforts to deliver the RNA.

血脑屏障（BBB）是治疗中枢神经系统（CNS）疾病，特别是侵袭性脑癌，如胶质母细胞瘤（GBM）和髓母细胞瘤（MB）的关键挑战。RNA疗法利用内源性细胞机制来调节基因表达，靶向以前不可药物的途径。RNA和CRISPR基因疗法具有改变脑癌的潜力，但需要在增强药物跨血脑屏障运输方面取得突破。虽然在非中枢神经系统疾病中的临床成就证实了它们的疗效，但跨学科合作对于推进纳米颗粒（NPs）的工程、免疫逃避和非侵入性递送至关重要。脂质纳米颗粒（LNPs）和病毒载体在脑癌的临床转化中起着重要作用。靶向治疗（如GLUT1、RVG肽、ApoE模拟肽）和非侵入性给药（如聚焦超声）方面的创新对于克服血脑屏障的局限性至关重要。这篇综述强调了可用于将基于RNA的治疗方法传递到大脑的不同策略，并总结了最近在传递RNA方面的临床努力。

{"title":"Nanoparticulate delivery and targeting of RNA to the brain","authors":"Aditya Gupta , Raghu Ramanathan , Chittalsinh M. Raulji , Ram I. Mahato","doi":"10.1016/j.bbcan.2025.189480","DOIUrl":"10.1016/j.bbcan.2025.189480","url":null,"abstract":"<div><div>The blood-brain barrier (BBB) presents a critical challenge in treating central nervous system (CNS) disorders, particularly aggressive brain cancers such as glioblastoma (GBM) and medulloblastoma (MB). RNA therapies exploit endogenous cellular machinery to modulate gene expression, targeting previously undruggable pathways. RNA and CRISPR gene therapies hold transformative potential for brain cancer but demand breakthroughs for enhanced drug transport across the BBB. While clinical achievements in non-CNS diseases validate their efficacy, interdisciplinary collaboration is essential to advance nanoparticles (NPs) engineering, immune evasion, and non-invasive delivery for CNS applications. NPs are indispensable for advancing RNA therapies in brain cancer, with lipid nanoparticles (LNPs) and viral vectors leading clinical translation. Innovations in targeting (e.g., GLUT1, RVG peptide, ApoE mimetic peptide) and non-invasive delivery (e.g., focused ultrasound) are critical to overcome the BBB limitations. This review highlights the different strategies that can be utilized to deliver RNA-based therapies to the brain and summarizes the recent clinical efforts to deliver the RNA.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 6","pages":"Article 189480"},"PeriodicalIF":9.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145412479","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}

引用次数: 0

Decoding the epigenetic landscape: ctDNA methylation as a game-changer in hepatocellular carcinoma management 解码表观遗传景观：ctDNA甲基化作为肝细胞癌管理的游戏规则改变者。

IF 9.7 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Reviews on cancer

Pub Date : 2025-11-01 DOI: 10.1016/j.bbcan.2025.189497

Dexin Yang , Yueru Yao , Fenfang Gui , Wuxuan Mei , Changchun Zeng

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.

肝细胞癌（HCC）是一个紧迫的全球健康问题，传统的诊断方法，如甲胎蛋白（AFP）和超声检查，在早期识别和预后可靠性方面存在局限性。循环肿瘤DNA （ctDNA）甲基化最近作为一种创新的“液体活检”生物标志物受到关注，通过非侵入性检测提供表观遗传特征和早期疾病信号。这篇综述阐明了DNA甲基化在HCC中的机制作用，强调了其对关键致癌级联反应及其进展依赖性改变的调节。此外，先进的检测技术，如基于限制性内切酶、基于富集和基于亚硫酸盐转化的方法，在HCC中进行了评估。此外，ctDNA甲基化在HCC早期检测、预后评估和治疗监测方面的临床适用性进行了评估。这篇综述全面概述了目前阻碍正在进行的研究成功临床转化的障碍。此外，它概述了潜在的研究方向，以解决这些限制，并促进研究结果快速转化为临床实践。最终，ctDNA甲基化在解读HCC的表观遗传谱方面提供了重大进展，对精确肿瘤学和患者预后有潜在的好处。

{"title":"Decoding the epigenetic landscape: ctDNA methylation as a game-changer in hepatocellular carcinoma management","authors":"Dexin Yang , Yueru Yao , Fenfang Gui , Wuxuan Mei , 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}

引用次数: 0

The mechanics of anoikis resistance in cancer 癌症耐药机制。

IF 9.7 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Reviews on cancer

Pub Date : 2025-11-01 DOI: 10.1016/j.bbcan.2025.189498

Michela Corsini , Mattia Domenichini , Elisa Moreschi , Stefania Mitola

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.

转移性癌细胞表现出非凡的能力来抵抗与细胞外基质分离和转移相关的机械和生化挑战。在这一过程中，一个关键的适应机制是对疾病的抵抗。在这篇综述中，我们探讨了使癌细胞抵抗疾病的分子和生物物理机制，重点是机械转导。我们讨论了整合素信号、YAP/TAZ通路、机械敏感离子通道和肌动球蛋白收缩性在机械应力条件下维持存活中的作用。此外，我们强调了可溶性介质的新兴贡献，特别是肌因子鸢尾素，它通过激活通常由基质接合触发的生存途径来作为机械模拟物。我们还研究了不同肿瘤类型和转移途径的机械异质性如何影响环境特异性适应策略。通过连接物理力量和细胞存活信号，本综述强调机械转导是转移能力的基本驱动因素，也是治疗干预的一个有希望的靶点。

{"title":"The mechanics of anoikis resistance in cancer","authors":"Michela Corsini , Mattia Domenichini , Elisa Moreschi , 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}

引用次数: 0

mRNA cancer vaccine: A novel and potential immunotherapy for multiple myeloma mRNA癌症疫苗：一种新的和潜在的多发性骨髓瘤免疫疗法。

IF 9.7 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Reviews on cancer

Pub Date : 2025-11-01 DOI: 10.1016/j.bbcan.2025.189493

Yiming Feng , Yufeng Du , Chengtao Zhang , Fang Xie , Jinsong Yan

Multiple myeloma (MM) is a malignant haematologic tumour originating from bone marrow plasma cells, characterised by the abnormal proliferation of monoclonal plasma cells, invasion of the bone marrow, and resulting end-organ damage, with continuous clinical progression. Although standardised treatment regimens and the application of novel cellular immunotherapies have helped control disease progression, the risks of drug resistance and relapse remain, and a complete cure is currently not achievable. mRNA cancer vaccines aim to target personalized neoantigens, inducing strong and specific anti-tumour immune responses, and have garnered widespread attention for their tremendous potential in cancer prevention and treatment. Compared to traditional cancer vaccine platforms, mRNA cancer vaccines offer unique advantages such as high safety, strong immunogenicity, personalized targeted immunotherapy, shorter development cycles, and lower costs, making them a revolutionary tool for achieving the goals of precision medicine. Given the unique advantages of MM, such as antigen lineage specificity, pathological mechanism and therapeutic needs alignment, clear safety profile and treatment endpoints, clinical window, and compatibility with multi-strategy combination therapies, we believe that exploring the use of mRNA cancer vaccines for the treatment of MM is both necessary and promising. In this review, we aimed to summarize the progress of immunotherapy for MM and the current application status of various antigens and vaccines. On this basis, we analysed the specificity and feasibility of mRNA cancer vaccines in MM and proposed strategies for their clinical management and optimisation. We believe that mRNA cancer vaccines have the potential to redefine the treatment paradigm for MM, offering new solutions for patients with refractory and relapsed disease.

多发性骨髓瘤（Multiple myeloma， MM）是一种起源于骨髓浆细胞的恶性血液学肿瘤，其特点是单克隆浆细胞异常增殖，侵袭骨髓，导致终末器官损害，临床进展不断。尽管标准化的治疗方案和新型细胞免疫疗法的应用有助于控制疾病的进展，但耐药和复发的风险仍然存在，目前无法实现完全治愈。mRNA肿瘤疫苗以个体化新抗原为靶点，诱导强而特异性的抗肿瘤免疫反应，在癌症预防和治疗方面具有巨大潜力，受到广泛关注。与传统的癌症疫苗平台相比，mRNA癌症疫苗具有安全性高、免疫原性强、个性化靶向免疫治疗、开发周期短、成本低等独特优势，是实现精准医疗目标的革命性工具。鉴于MM的独特优势，如抗原谱系特异性、病理机制和治疗需求一致性、明确的安全性和治疗终点、临床窗口以及与多策略联合治疗的兼容性，我们认为探索使用mRNA癌症疫苗治疗MM是必要的和有希望的。本文就MM的免疫治疗进展及各种抗原和疫苗的应用现状进行综述。在此基础上，我们分析了mRNA癌症疫苗在MM中的特异性和可行性，并提出了其临床管理和优化策略。我们相信mRNA癌症疫苗有可能重新定义MM的治疗模式，为难治性和复发性疾病患者提供新的解决方案。

{"title":"mRNA cancer vaccine: A novel and potential immunotherapy for multiple myeloma","authors":"Yiming Feng , Yufeng Du , Chengtao Zhang , Fang Xie , Jinsong Yan","doi":"10.1016/j.bbcan.2025.189493","DOIUrl":"10.1016/j.bbcan.2025.189493","url":null,"abstract":"<div><div>Multiple myeloma (MM) is a malignant haematologic tumour originating from bone marrow plasma cells, characterised by the abnormal proliferation of monoclonal plasma cells, invasion of the bone marrow, and resulting end-organ damage, with continuous clinical progression. Although standardised treatment regimens and the application of novel cellular immunotherapies have helped control disease progression, the risks of drug resistance and relapse remain, and a complete cure is currently not achievable. mRNA cancer vaccines aim to target personalized neoantigens, inducing strong and specific anti-tumour immune responses, and have garnered widespread attention for their tremendous potential in cancer prevention and treatment. Compared to traditional cancer vaccine platforms, mRNA cancer vaccines offer unique advantages such as high safety, strong immunogenicity, personalized targeted immunotherapy, shorter development cycles, and lower costs, making them a revolutionary tool for achieving the goals of precision medicine. Given the unique advantages of MM, such as antigen lineage specificity, pathological mechanism and therapeutic needs alignment, clear safety profile and treatment endpoints, clinical window, and compatibility with multi-strategy combination therapies, we believe that exploring the use of mRNA cancer vaccines for the treatment of MM is both necessary and promising. In this review, we aimed to summarize the progress of immunotherapy for MM and the current application status of various antigens and vaccines. On this basis, we analysed the specificity and feasibility of mRNA cancer vaccines in MM and proposed strategies for their clinical management and optimisation. We believe that mRNA cancer vaccines have the potential to redefine the treatment paradigm for MM, offering new solutions for patients with refractory and relapsed disease.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 6","pages":"Article 189493"},"PeriodicalIF":9.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145491067","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}

引用次数: 0

The double-edged sword of IRF7: “Guardian” or “traitor” of tumors? From mechanistic contradictions to therapeutic revolution IRF7的双刃剑：肿瘤的“守护者”还是“叛徒”？从机械矛盾到治疗革命。

IF 9.7 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Reviews on cancer

Pub Date : 2025-11-01 DOI: 10.1016/j.bbcan.2025.189501

Siyu Li , Qiong Luo , Jiali Hu , Xiaobing Duan , Guihai Zhang

Abstract

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.

干扰素调节因子7 （IRF7）正在成为癌症生物学中一个关键而矛盾的调节剂，既可以作为肿瘤抑制因子，也可以作为环境依赖性的致癌驱动因子。这篇综述不仅涵盖了增殖信号、免疫逃避、细胞凋亡抵抗和转移等经典特征，而且还包括了Hanahan在2022年增加的四个新兴特征，即表型可塑性、非突变表观遗传重编程、多态微生物组和衰老细胞的动态平衡。在机制上，IRF7整合了转录调控、翻译后修饰（PTMs）和微环境线索来协调不同的致癌过程，导致组织特异性和时空功能二分法。此外，本综述强调了IRF7在治疗环境中的双重潜力——在某些情况下增强抗肿瘤免疫和干扰素信号，而在其他情况下促进免疫抑制、治疗抵抗或肿瘤进展。最近针对IRF7的药物开发进展，如表观遗传调节、激酶抑制和基于外泌体的递送，为精确癌症治疗提供了有希望的途径。然而，IRF7的功能异质性需要一种细致入微的治疗方法，强调生物标志物引导的分层和时空特异性干预。总的来说，IRF7是一个与免疫、代谢和致癌途径相关的关键调控枢纽，对未来的癌症诊断、预后和治疗策略具有重要意义。

{"title":"The double-edged sword of IRF7: “Guardian” or “traitor” of tumors? From mechanistic contradictions to therapeutic revolution","authors":"Siyu Li , Qiong Luo , Jiali Hu , Xiaobing Duan , 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}

引用次数: 0

Role of CCL8 in cancer immunity and tumor progression: Implications for cancer treatment CCL8在癌症免疫和肿瘤进展中的作用：对癌症治疗的意义

IF 9.7 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Reviews on cancer

Pub Date : 2025-11-01 DOI: 10.1016/j.bbcan.2025.189502

Jiwoo Jeong, Eun-Sook Kim

The C-C motif chemokine ligand 8 (CCL8) is a key chemokine that plays a prominent role in immune cells, inflammatory responses, and the progression of various pathologies. This review initially outlines the structural characteristics of CCL8, its receptor-binding properties, and its involvement in various signaling pathways. We integrated database evidence demonstrating how CCL8 expression in various cancers affects tumor growth, migration, and invasion, thereby influencing patient prognosis. Subsequently, we explored how CCL8 interacts with immune cells to either promote or suppress tumor development and assessed whether its expression correlates with immune cell infiltration within the tumor immune microenvironment in different cancer types. Furthermore, we underscore the potential of CCL8 as a biomarker for the progression of cancer and other diseases, and its clinical relevance in predicting therapeutic responses via targeted antagonists and receptor blockade. Finally, by integrating current insights into the role of CCL8 in tumor cell proliferation within the cancer immune microenvironment, this review aims to elucidate the biological significance of CCL8 and facilitate the development of novel diagnostic and therapeutic strategies.

C-C基序趋化因子配体8 （CCL8）是一种关键的趋化因子，在免疫细胞、炎症反应和各种病理进展中发挥着重要作用。本文首先概述了CCL8的结构特征、受体结合特性及其参与的各种信号通路。我们整合了数据库证据，证明CCL8在各种癌症中的表达如何影响肿瘤生长、迁移和侵袭，从而影响患者预后。随后，我们探索了CCL8如何与免疫细胞相互作用，促进或抑制肿瘤的发展，并评估了其表达是否与不同癌症类型肿瘤免疫微环境中的免疫细胞浸润相关。此外，我们强调了CCL8作为癌症和其他疾病进展的生物标志物的潜力，以及它在通过靶向拮抗剂和受体阻断预测治疗反应方面的临床相关性。最后，通过整合目前对肿瘤免疫微环境中CCL8在肿瘤细胞增殖中的作用的见解，本综述旨在阐明CCL8的生物学意义，并促进新的诊断和治疗策略的发展。

{"title":"Role of CCL8 in cancer immunity and tumor progression: Implications for cancer treatment","authors":"Jiwoo Jeong, Eun-Sook Kim","doi":"10.1016/j.bbcan.2025.189502","DOIUrl":"10.1016/j.bbcan.2025.189502","url":null,"abstract":"<div><div>The C-C motif chemokine ligand 8 (CCL8) is a key chemokine that plays a prominent role in immune cells, inflammatory responses, and the progression of various pathologies. This review initially outlines the structural characteristics of CCL8, its receptor-binding properties, and its involvement in various signaling pathways. We integrated database evidence demonstrating how CCL8 expression in various cancers affects tumor growth, migration, and invasion, thereby influencing patient prognosis. Subsequently, we explored how CCL8 interacts with immune cells to either promote or suppress tumor development and assessed whether its expression correlates with immune cell infiltration within the tumor immune microenvironment in different cancer types. Furthermore, we underscore the potential of CCL8 as a biomarker for the progression of cancer and other diseases, and its clinical relevance in predicting therapeutic responses via targeted antagonists and receptor blockade. Finally, by integrating current insights into the role of CCL8 in tumor cell proliferation within the cancer immune microenvironment, this review aims to elucidate the biological significance of CCL8 and facilitate the development of novel diagnostic and therapeutic strategies.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 6","pages":"Article 189502"},"PeriodicalIF":9.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145643916","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}

引用次数: 0