Biochimica et biophysica acta. Reviews on cancer最新文献_第2页

Precision cytokine modulation to overcome tumor microenvironment-driven resistance to immune checkpoint blockade 精确的细胞因子调节克服肿瘤微环境驱动的免疫检查点阻断抗性。

IF 9.7 1区医学

Biochimica et biophysica acta. Reviews on cancer Pub Date : 2026-04-01 Epub Date: 2026-01-23 DOI: 10.1016/j.bbcan.2026.189536

Xiaodong Wang , Junjie Wang , Qianqian Wang , Gouping Ding , Yiping Huang , Yeqian Feng

{"title":"Precision cytokine modulation to overcome tumor microenvironment-driven resistance to immune checkpoint blockade","authors":"Xiaodong Wang , Junjie Wang , Qianqian Wang , Gouping Ding , Yiping Huang , Yeqian Feng","doi":"10.1016/j.bbcan.2026.189536","DOIUrl":"10.1016/j.bbcan.2026.189536","url":null,"abstract":"<div><div>Immune checkpoint inhibitors (ICIs) can elicit durable remissions, yet most solid tumors show primary non-response or acquired resistance because the tumor microenvironment (TME) limits T-cell priming, trafficking and effector fitness. Cytokines orchestrate these barriers by shaping spatial immune architecture, regulating suppressive myeloid programmes and inducing inhibitory ligands such as PD-L1. In this Review, we synthesize mechanistic and clinical evidence and propose a push–pull framework for cytokine modulation during checkpoint blockade: locally amplifying Th1/CTL-supporting signals (IL-2/IL-12/IL-15 and type I/II interferons) while selectively attenuating dominant suppressive circuits (TGF-β, IL-6/STAT3, IL-8–CXCR1/2, IL-10 and TNF-driven exhaustion). We critically contrast successful and failed cytokine–ICI combinations, highlighting how systemic exposure, network redundancy and counter-regulatory feedback have constrained several engineered agonists and explain why certain blockade strategies can improve efficacy while reducing immune-related toxicity. We discuss next-generation solutions—tumor-activated pro-cytokines, intratumoral gene delivery and immunocytokines—that concentrate activity within resistant niches and widen the therapeutic window. Finally, we outline actionable biomarkers, including transcriptomic signatures, plasma cytokine kinetics, myeloid/neutrophil metrics and spatial TME profiling, to stratify patients and guide dosing, sequencing and adaptive add-on strategies. Rational, biomarker-guided cytokine modulation offers a path to convert immune-excluded tumors into durable ICI responders.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1881 2","pages":"Article 189536"},"PeriodicalIF":9.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146047510","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

Cancer-associated fibroblasts-derived exosomes in colorectal cancer progression: Mechanism and therapeutic opportunities 结直肠癌进展中癌症相关成纤维细胞衍生外泌体：机制和治疗机会

IF 9.7 1区医学

Biochimica et biophysica acta. Reviews on cancer Pub Date : 2026-04-01 Epub Date: 2026-01-27 DOI: 10.1016/j.bbcan.2026.189545

Linling Yang , Parastoo Akbarabadi , Sadegh Babashah

{"title":"Cancer-associated fibroblasts-derived exosomes in colorectal cancer progression: Mechanism and therapeutic opportunities","authors":"Linling Yang , Parastoo Akbarabadi , Sadegh Babashah","doi":"10.1016/j.bbcan.2026.189545","DOIUrl":"10.1016/j.bbcan.2026.189545","url":null,"abstract":"<div><div>Colorectal cancer (CRC) progression is profoundly shaped by the tumor microenvironment. Among stromal components, cancer-associated fibroblasts (CAFs) release small extracellular vesicles (exosomes) that deliver miRNAs, lncRNAs, circRNAs, proteins, and metabolites to malignant and immune cells. In CRC, CAF-derived exosomes (CAF-Exo) drive epithelial–mesenchymal transition, sustain stemness, stimulate angiogenesis, suppress antitumor immunity, and promote resistance to fluoropyrimidines and oxaliplatin. Representative mechanisms include exosomal miR-92a-3p activation of Wnt/β-catenin signaling, the lncRNA WEE2-AS1–mediated suppression of Hippo restraint with YAP activation, and circRNA cargos that reprogram autophagy or endothelial dynamics. Circulating CAF-Exo signatures are emerging as minimally invasive biomarkers for diagnosis, prognosis, and therapy stratification. However, translation remains limited by CAF heterogeneity, cargo variability, and incomplete in vivo characterization of vesicle dynamics. Therapeutic opportunities include blockade of exosome biogenesis or uptake, pharmacologic reprogramming of CAFs, and engineering vesicles to deliver targeted inhibitors or RNA-based therapeutics. This review synthesizes current mechanistic insights, evaluates biomarker potential, and outlines clinical priorities for targeting CAF-exosomal pathways in CRC.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1881 2","pages":"Article 189545"},"PeriodicalIF":9.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146075709","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 signal hijacker: How tumors co-opt chemical, electrical, and mechanical cues to thrive 信号劫机者：肿瘤如何利用化学、电子和机械信号来茁壮成长。

IF 9.7 1区医学

Biochimica et biophysica acta. Reviews on cancer Pub Date : 2026-04-01 Epub Date: 2026-02-10 DOI: 10.1016/j.bbcan.2026.189556

Yong-Fei Wang , Si-Yuan Wang , Zhuo-Ying He , Ming-Zhu Jin , Wen-Zhen Yuan , Wei-Lin Jin

{"title":"The signal hijacker: How tumors co-opt chemical, electrical, and mechanical cues to thrive","authors":"Yong-Fei Wang , Si-Yuan Wang , Zhuo-Ying He , Ming-Zhu Jin , Wen-Zhen Yuan , Wei-Lin Jin","doi":"10.1016/j.bbcan.2026.189556","DOIUrl":"10.1016/j.bbcan.2026.189556","url":null,"abstract":"<div><div>To survive within hostile microenvironments, tumors exploit a coordinated, tri-dimensional signaling network encompassing chemical, electrical, and mechanical communication. This enables them to reshape the tumor ecosystem into a supportive niche. This review introduces a unified “signal hijacking” framework to decipher this process. First, chemical hijacking redirects metabolites through mechanisms like lactate shuttling and nucleotide theft via tunneling nanotubes and extracellular vesicles while subverting cytokine networks through TGFβ-dependent immunosuppression. Second, bioelectrical hijacking capitalizes on ion gradient alterations via V-ATPase-driven depolarization and intercellular communication through gap junction-transmitted calcium waves. Third, mechanical hijacking involves ECM restructuring through LOXL2-mediated fibrosis and cadherin tension modulation via β-catenin liberation during cellular force competitions. The hijacking of these signals reprograms the genetic and protein landscape of cells within the tumor microenvironment, fostering an environment suitable for tumor survival. Accordingly, therapeutic strategies targeting these vulnerabilities aim to disrupt tumor communication through three primary modalities: chemical interception (e.g., LDHA and MCT1 inhibitors), bioelectrical recalibration (e.g., Kv1.3 activators and TRPV1 antagonists), and mechanical intervention (e.g., LOXL2 antibodies and Piezo1 inhibitors). This “signal hijacking “paradigm recasts cancer as a battle for communicative control within the ecosystem. We thus propose that reestablishing system-wide signaling homeostasis, rather than pursuing pure cytoreduction, represents a fundamental strategy to overcome therapy resistance.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1881 2","pages":"Article 189556"},"PeriodicalIF":9.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146183738","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

Targeting glycolysis in prostate cancer: Molecular mechanisms and therapeutic advances 靶向糖酵解治疗前列腺癌：分子机制和治疗进展

IF 9.7 1区医学

Biochimica et biophysica acta. Reviews on cancer Pub Date : 2026-04-01 Epub Date: 2026-01-16 DOI: 10.1016/j.bbcan.2026.189537

Jiexiang Zhang , Tongtong Zhang , Dexin Song , Dongliang Xu

{"title":"Targeting glycolysis in prostate cancer: Molecular mechanisms and therapeutic advances","authors":"Jiexiang Zhang , Tongtong Zhang , Dexin Song , Dongliang Xu","doi":"10.1016/j.bbcan.2026.189537","DOIUrl":"10.1016/j.bbcan.2026.189537","url":null,"abstract":"<div><div>Prostate cancer (PCa) is the second most common cancer among men worldwide and poses a significant threat to male health. A key feature of tumor progression is metabolic reprogramming, which involves the abnormal activation of glycolysis. This metabolic process supports PCa proliferation, metastasis, and drug resistance through rapid energy production, the provision of biosynthetic precursors, and the remodeling of the tumor microenvironment (TME). Key enzymes such as hexokinase 2 (HK2), phosphofructokinase (PFK), pyruvate kinase M2 (PKM2), glucose transporters (GLUTs), and lactate dehydrogenase A (LDHA) play pivotal roles in regulating aerobic glycolysis in PCa cells. Glycolytic enzymes are modulated by a variety of mechanisms, including the PI3K/AKT and AMPK signaling pathways, hypoxia-inducible factor 1α (HIF-1α), c-Myc, and non-coding RNAs. Current therapeutic strategies targeting glycolysis include natural products and small-molecule inhibitors. Targeting glycolysis presents novel opportunities to address existing limitations in PCa management. This review discusses the advances, challenges, and future research directions in glycolysis-focused PCa studies, providing a theoretical foundation for the development of precise metabolic interventions.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1881 2","pages":"Article 189537"},"PeriodicalIF":9.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145996195","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

Acinar cell plasticity and subtype specification during acinar-to-ductal metaplasia and pancreatic cancer progression 腺泡到导管化生和胰腺癌进展过程中的腺泡细胞可塑性和亚型规范。

IF 9.7 1区医学

Biochimica et biophysica acta. Reviews on cancer Pub Date : 2026-04-01 Epub Date: 2026-02-03 DOI: 10.1016/j.bbcan.2026.189549

Bharti Gautam , Anurati Sharma , Mamatha Jatavath , Ramesh Pothuraju , Sanjib Chaudhary , Shailendra K. Gautam , Rakesh Bhatia

{"title":"Acinar cell plasticity and subtype specification during acinar-to-ductal metaplasia and pancreatic cancer progression","authors":"Bharti Gautam , Anurati Sharma , Mamatha Jatavath , Ramesh Pothuraju , Sanjib Chaudhary , Shailendra K. Gautam , Rakesh Bhatia","doi":"10.1016/j.bbcan.2026.189549","DOIUrl":"10.1016/j.bbcan.2026.189549","url":null,"abstract":"<div><div>The onset and progression of pancreatic ductal adenocarcinoma (PDAC) influence acinar cells, leading to metaplastic and neoplastic adaptations. Lineage tracing experiments demonstrate the inherent plasticity of pancreatic acinar cells towards various subtypes, including tuft cells (TCs), enteroendocrine cells, gastric pit-like cells, and senescent cells. These cell types contribute to the injury resolution and maintenance of tissue homeostasis. Further transition of certain acinar subtypes, such as TCs, into metaplastic neuroendocrine cells and neural-like progenitors results in an aggressive PDAC phenotype and poor prognosis. This review describes the factors driving the specification trajectory of pancreatic acinar cell subtypes, their metabolic and functional preferences, particularly in the context of tumor microenvironment (TME) modulation, and their utility as an attractive target for improved therapy response. We emphasize the roles of TME components, including cancer-associated fibroblasts, immune cells, cancer-associated mucins, and various signaling mediators, in acinar subtype specification. The review highlights the concept of acinar metaplastic duct heterogeneity and its implications for targeting aggressive acinar subtypes to improve survival outcomes.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1881 2","pages":"Article 189549"},"PeriodicalIF":9.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146127669","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

Protein palmitoylation and immune regulation in pancreatic ductal adenocarcinoma: Integrating insights from cross-cancer studies 胰腺导管腺癌中的蛋白棕榈酰化和免疫调节：来自交叉癌症研究的整合见解。

IF 9.7 1区医学

Biochimica et biophysica acta. Reviews on cancer Pub Date : 2026-04-01 Epub Date: 2026-01-14 DOI: 10.1016/j.bbcan.2026.189532

Xiaotong Cui , Changlei Li , Xue Zhong , Ao Sun , Yingying Lan , Zusen Wang

{"title":"Protein palmitoylation and immune regulation in pancreatic ductal adenocarcinoma: Integrating insights from cross-cancer studies","authors":"Xiaotong Cui , Changlei Li , Xue Zhong , Ao Sun , Yingying Lan , Zusen Wang","doi":"10.1016/j.bbcan.2026.189532","DOIUrl":"10.1016/j.bbcan.2026.189532","url":null,"abstract":"<div><div>Pancreatic ductal adenocarcinoma (PDAC) is characterized by an immunologically “cold” tumor microenvironment (TME), marked by a dense stromal barrier, impaired antigen presentation, and extensive infiltration of immunosuppressive cells. In recent years, protein S-palmitoylation, a reversible lipid modification, has emerged as a critical mechanism regulating immune signaling, receptor trafficking, and membrane localization of immune-related proteins. This review highlights the multifaceted roles of S-palmitoylation in shaping the immunological landscape of PDAC. We systematically discuss its involvement in immune checkpoint regulation, T-cell activation, antigen presentation, and the function of myeloid-derived suppressor cells (MDSCs), integrating evidence from both PDAC and other cancer types. Special attention is given to key palmitoylated molecules, including programmed death-ligand 1 (PD-L1), cluster of differentiation 80 (CD80), lymphocyte-specific protein tyrosine kinase (LCK), linker for activation of T cells (LAT), interferon-induced transmembrane proteins (IFITMs), and major histocompatibility complex class I (MHC-I), and their potential roles in the immunosuppressive network of PDAC. Moreover, we explore therapeutic strategies targeting palmitoylation, such as the use of selective palmitoyltransferase inhibitors, the design of palmitoylation-deficient CAR-T cells, and the development of nanotechnology-based delivery platforms. By incorporating cross-cancer insights, we propose that palmitoylation is a promising regulatory axis for reprogramming the PDAC immune microenvironment and overcoming resistance to immunotherapy.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1881 2","pages":"Article 189532"},"PeriodicalIF":9.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145992174","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

From bone homeostasis to skeletal metastasis and osteosarcoma: Insights into osteoclast and osteoblast roles in bone remodelling and cancer 从骨稳态到骨转移和骨肉瘤：破骨细胞和成骨细胞在骨重塑和癌症中的作用。

IF 9.7 1区医学

Biochimica et biophysica acta. Reviews on cancer Pub Date : 2026-04-01 Epub Date: 2026-02-03 DOI: 10.1016/j.bbcan.2026.189551

Valentina Kottmann, Michael Nienhaus, Philipp Drees, Erol Gercek, Ulrike Ritz

{"title":"From bone homeostasis to skeletal metastasis and osteosarcoma: Insights into osteoclast and osteoblast roles in bone remodelling and cancer","authors":"Valentina Kottmann, Michael Nienhaus, Philipp Drees, Erol Gercek, Ulrike Ritz","doi":"10.1016/j.bbcan.2026.189551","DOIUrl":"10.1016/j.bbcan.2026.189551","url":null,"abstract":"<div><div>Bone is a highly dynamic tissue undergoing continuous remodelling through the coordinated actions of osteocytes, osteoblasts and osteoclasts. This process is tightly regulated by key signalling pathways, including the RANK/RANKL/Osteoprotegerin system, which governs bone resorption and formation. In addition, the CXCL12/CXCR4 axis and G-protein-coupled receptor 4 (GPCR4) play crucial roles in bone development, remodelling, and pathological conditions such as cancer progression. Skeletal metastases arise from complex interactions between tumour cells and the bone microenvironment, facilitating arrest, extravasation, and colonisation at secondary sites. In osteosarcoma and metastatic cancers, these molecular mechanisms contribute to tumour growth, bone degradation, bone formation and disease progression. This review highlights the intricate crosstalk between bone remodelling pathways and tumour cell invasion, providing insights into potential therapeutic targets for osteosarcoma and bone metastases.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1881 2","pages":"Article 189551"},"PeriodicalIF":9.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146127574","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

Innovations in HER2-targeted therapy: A comprehensive review of trastuzumab deruxtecan her2靶向治疗的创新：曲妥珠单抗德鲁西替康的全面回顾

IF 9.7 1区医学

Biochimica et biophysica acta. Reviews on cancer Pub Date : 2026-04-01 Epub Date: 2026-02-03 DOI: 10.1016/j.bbcan.2026.189550

Haitong Xie , Xin Wang , Peixuan Zhang , Qintong Li , Jie Chen

{"title":"Innovations in HER2-targeted therapy: A comprehensive review of trastuzumab deruxtecan","authors":"Haitong Xie , Xin Wang , Peixuan Zhang , Qintong Li , Jie Chen","doi":"10.1016/j.bbcan.2026.189550","DOIUrl":"10.1016/j.bbcan.2026.189550","url":null,"abstract":"<div><div>Trastuzumab deruxtecan (T-DXd) has emerged as a revolutionary antibody–drug conjugate (ADC) that has shown remarkable clinical efficacy across multiple HER2-expressing tumor types. Comprising a humanized anti-HER2 monoclonal antibody linked to a potent topoisomerase I inhibitor via a cleavable and stable tetrapeptide-based linker, T-DXd integrates the specificity of targeted therapy with the cytotoxic potency of chemotherapy. As the most promising ADC in the era of precision oncology, T-DXd has been approved to treat a series of malignant tumors. However, its widespread clinical application is challenged by treatment-related adverse events, the emergence of drug resistance, and uncertainties in biomarker-guided patient selection. This review provides a comprehensive overview of T-DXd’s molecular design, mechanisms of action, and major findings from key clinical trials. It also examines resistance pathways and safety considerations, and discusses strategies to optimize therapeutic outcomes, including rational combination approaches with immune checkpoint inhibitors or other targeted agents. Finally, we explore future directions in T-DXd development, emphasizing the importance of precision medicine, biomarker refinement, and next-generation ADC engineering to further enhance efficacy and safety.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1881 2","pages":"Article 189550"},"PeriodicalIF":9.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146127580","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

SAG/RBX2/ROC2/RNF7 dual E3 ligase: From target identification, validation to drug discovery SAG/RBX2/ROC2/RNF7双E3连接酶：从靶点鉴定、验证到药物发现

IF 9.7 1区医学

Biochimica et biophysica acta. Reviews on cancer Pub Date : 2026-04-01 Epub Date: 2026-01-27 DOI: 10.1016/j.bbcan.2026.189546

Qing Yu , Shizhen Zhang , Zhijian Li , Ting Liang , Yi Sun

{"title":"SAG/RBX2/ROC2/RNF7 dual E3 ligase: From target identification, validation to drug discovery","authors":"Qing Yu , Shizhen Zhang , Zhijian Li , Ting Liang , Yi Sun","doi":"10.1016/j.bbcan.2026.189546","DOIUrl":"10.1016/j.bbcan.2026.189546","url":null,"abstract":"<div><div>SAG (Sensitive to Apoptosis Gene), also known as RBX2/ROC2/RNF7, was originally cloned as a redox-inducible gene encoding a cysteine-enriched antioxidant protein. SAG was subsequently characterized as the second family member of the RBX with RING domain, essential for E3 ligase activity in both ubiquitylation and neddylation. Data accumulated over the past 26 years have shown that SAG is overexpressed in many types of human cancer tissues with positive correlation of poor patient survival. Functional studies have revealed that SAG is essential for cancer cell growth, and for tumorigenesis induced by oncogene activation and tumor suppressor inactivation in several genetically modified mouse models. Mechanistically, SAG acts as a catalytic subunit of CRL5 as well as CRL1 to ubiquitylate and degrade mainly tumor suppressor substrates, whereas SAG knockdown or knockout causes their accumulation to inhibit the growth and survival of cancer cells, and tumor progression. Thus, SAG E3 is emerging as an attractive anti-cancer target with drug discovery of small molecule inhibitors and PROTAC degraders being currently pursued. Here, we provide a comprehensive literature review on SAG, from its molecular cloning, biochemical activities, and biological function, to SAG validation as an anti-cancer target, and finally to the drug discovery efforts of SAG targeting agents. The perspectives are also proposed for current challenges and future directions on the study of SAG-associated neddylation-CRLs.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1881 2","pages":"Article 189546"},"PeriodicalIF":9.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146088349","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

Histone acetyltransferase HBO1 in cancer biology: Essential mechanisms and implications for targeted therapeutics 组蛋白乙酰转移酶HBO1在癌症生物学中的作用：靶向治疗的基本机制和意义。

IF 9.7 1区医学

Biochimica et biophysica acta. Reviews on cancer Pub Date : 2026-04-01 Epub Date: 2026-01-18 DOI: 10.1016/j.bbcan.2026.189533

Alissa D. Marchione, Katie L. Kathrein

{"title":"Histone acetyltransferase HBO1 in cancer biology: Essential mechanisms and implications for targeted therapeutics","authors":"Alissa D. Marchione, Katie L. Kathrein","doi":"10.1016/j.bbcan.2026.189533","DOIUrl":"10.1016/j.bbcan.2026.189533","url":null,"abstract":"<div><div>The histone acetyltransferase complex HBO1 (KAT7) is an oncogenic regulator across multiple cancers, promoting cell proliferation and migration. Though clinically important, no targeted therapies address HBO1 dysregulation. HBO1 forms complexes with MEAF6, JADE(1/2/3), ING(ING4/5), and BRPF1/2/3 to acetylate histones H3 and H4, especially at H3K14, promoting transcriptional activation and genomic stability. It colocalizes with active transcriptional sites and participates in gene regulation, DNA repair and replication. Most HBO1-associated cancer mutations are missense, though their effects remain unclear. Silencing HBO1 restores normal proliferation and gene expression, underscoring its oncogenic role. HBO1 activity supports cancer pathways, including apoptosis resistance, DNA damage response, and cell cycle regulation. The HBO1 inhibitor WM-3835 disrupts H3K14 acetylation, reducing tumor growth in several cancers. This review provides insights into the function of HBO1 in cancer, especially in histone acetylation, ubiquitination, stem cell maintenance, and pro- and anti-oncogenic signaling. Understanding the roles of HBO1 may guide new epigenetic therapies for HBO1-driven malignancies.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1881 2","pages":"Article 189533"},"PeriodicalIF":9.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146013816","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