Acta Pharmaceutica Sinica. B最新文献

{"title":"Tuning epigenetics to enhance cancer virotherapy","authors":"Yuanyuan Wang,&nbsp;Lanyi Zhang,&nbsp;Yunting Che,&nbsp;Fuhua Yang,&nbsp;Zhi-Jun Sun","doi":"10.1016/j.apsb.2026.06.045","DOIUrl":"10.1016/j.apsb.2026.06.045","url":null,"abstract":"<div><div>Cancer remains a major global health challenge, driving intensive research into novel therapeutic strategies. Oncolytic viruses (OVs) including herpesviruses, adenoviruses and echoviruses, have emerged as promising agents for cancer treatment, with several achieving regulatory approval. These viruses selectively lyse tumor cells and stimulate antitumor immunity. Nevertheless, their efficacy is constrained by limitations such as neutralization by serum factors and tumor cell resistance. Concurrently, epigenetic inhibitors modulate gene expression to suppress tumor proliferation and reshape immune responses. Recent advances highlight the strong synergistic potential of combining epigenetic inhibitors with oncolytic viruses. This strategy enhances viral replication and tumor cell killing, reprograms the tumor microenvironment, and ultimately improves therapeutic efficacy. Consequently, the integration of epigenetic modulators with OV therapy represents a promising frontier in oncology. This review comprehensively examines epigenetic inhibitors, with emphasis on their combined application with oncolytic viruses for cancer treatment.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 9","pages":"Pages 5566-5591"},"PeriodicalIF":14.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148949549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging organoids and organoids-on-chip platforms for translational development of antibody‒drug conjugates and next-generation bioconjugates","authors":"Zhuoliang Hu,&nbsp;Yuheng Liao,&nbsp;Mengxian Niu,&nbsp;Zhanghong Kong,&nbsp;Hugo Vankelecom,&nbsp;Jianjun Cheng,&nbsp;Michela Deleidi,&nbsp;Chenzhong Li,&nbsp;Zhengjin Jiang,&nbsp;Sumin Bian,&nbsp;Qiqin Wang","doi":"10.1016/j.apsb.2026.05.032","DOIUrl":"10.1016/j.apsb.2026.05.032","url":null,"abstract":"<div><div>The rapid evolution of antibody‒drug conjugates (ADCs) and emerging X–drug conjugates (XDCs) has revolutionized targeted cancer therapy, yet their clinical translation is severely bottlenecked by the lack of human-relevant preclinical models. To bridge this translational gap, patient-derived organoids and organoids-on-chip (OoC) platforms recapitulate key features of human tumor biology, offering powerful tools for investigating cancer heterogeneity and improving the predictive evaluation of bioconjugated therapeutics. In this review, we systematically summarize the current landscape and challenges of ADCs and XDCs development across existing preclinical models, critically discuss the concepts, biological principles and application potential of organoid- and OoC-based systems, and highlight recent global policy developments and collaborative initiatives shaping their translational implementation. Finally, we highlight key challenges and future perspectives for leveraging organoids and OoCs in the druggability assessment, optimization, and translational development of ADCs and XDCs.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 9","pages":"Pages 5509-5539"},"PeriodicalIF":14.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148949547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Direct pharmacological targeting of RAC1 by chlorogenic acid: A novel therapeutic approach for mesangial proliferative glomerulonephritis","authors":"Yilun Qu,&nbsp;Lingling Wu,&nbsp;Yong Wang,&nbsp;Fei Peng,&nbsp;Jie Zhang,&nbsp;Dan Pan,&nbsp;Tiantian Wang,&nbsp;Yena Zhou,&nbsp;Jikai Xia,&nbsp;Jiayi He,&nbsp;Chunru Shi,&nbsp;Yinghua Zhao,&nbsp;Xu Wang,&nbsp;Ran Liu,&nbsp;Yingjie Zhang,&nbsp;Jiaona Liu,&nbsp;Jie Wu,&nbsp;Shuwei Duan,&nbsp;Guangyan Cai,&nbsp;Ping Li,&nbsp;Xiangmei Chen","doi":"10.1016/j.apsb.2026.06.041","DOIUrl":"10.1016/j.apsb.2026.06.041","url":null,"abstract":"<div><div>Mesangial proliferative glomerulonephritis (MsPGN) is a common cause of end-stage renal disease, characterized by mesangial cell proliferation within glomeruli. Mesangial cell activation triggered by inflammation is a key factor in the development of MsPGN. However, effective therapeutic strategies targeting this process are still limited. Here, we uncovered, for the first time, the direct effects of chlorogenic acid (CGA), a naturally occurring small-molecule compound with anti-inflammatory and antiproliferative properties, on mesangial cells in an anti-Thy1 nephritis animal model. A multi-dimensional pharmacological platform integrating laser microdissection-coupled glomerular proteomics affinity deconvolution, surface plasmon resonance, molecular dynamics, and enzyme assays identified Ras-related C3 botulinum toxin substrate 1 (RAC1) as the direct target of CGA. Mechanistically, CGA competitively binds to the LYS15, PRO33, and THR34 amino acid residues—located within residues 57–65 of the GTP/GDP-binding domain of RAC1, inhibiting its activation and subsequently reducing AKT phosphorylation while suppressing Thrombospondin-1 secretion from mesangial cells—a key ligand for macrophage CD36 receptors. This interaction deactivates macrophages and lowers the levels of inflammatory cytokines, including TNF<em>α</em>, IL1<em>β</em>, and IL6. Significantly, as a novel natural RAC1 inhibitor, CGA disrupts mesangial-macrophage crosstalk by dual suppression of regional immunity and cellular proliferation, thus conferring renal protection in MsPGN models. Our findings highlight CGA as a promising pharmacotherapy, offering a mechanism-driven, natural product-based strategy to mitigate MsPGN progression.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 9","pages":"Pages 6080-6098"},"PeriodicalIF":14.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148940236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Self-assembled supramolecular nanoparticles of α-mangostin for targeted STING activation and enhanced tumor immunotherapy","authors":"Jiaqian Miao,&nbsp;Yuxin Liu,&nbsp;Sisi Chen,&nbsp;Yinxuan Zhou,&nbsp;Jun Liu,&nbsp;Danni Xu,&nbsp;Xuan Mo,&nbsp;Junjie Wang,&nbsp;Qianli Zhu,&nbsp;Chunyang Yu,&nbsp;Qiuhui Qian,&nbsp;Hongping Deng,&nbsp;Li Xu,&nbsp;Guangbo Ge","doi":"10.1016/j.apsb.2026.06.044","DOIUrl":"10.1016/j.apsb.2026.06.044","url":null,"abstract":"<div><div>Targeted activation of the stimulator of interferon genes (STING) signaling pathway represents a promising strategy to counteract immunosuppressive tumor microenvironments (TME) and elicit anti-tumor immunity. However, clinical translation of STING agonists has been strongly hindered by the challenges in achieving tumor-targeted STING activation. Here, we report a facile and efficient supramolecular self-assembly strategy for tumor-targeted STING activation of <em>α</em>-mangostin (MGT), a natural non-cyclic dinucleotide STING agonist. MGT can self-assemble into uniform supramolecular nanoparticles (MGT-SNPs) with 100% drug loading, driven by its inherent amphiphilic xanthone structure <em>via</em> multiple non-covalent interactions. The resulting MGT-SNPs (∼186.50 nm, negatively charged) demonstrate excellent colloidal stability, pH-responsive drug release, and enhanced cellular uptake <em>in vitro</em>. Furthermore, MGT-SNPs exhibit sufficient circulatory stability, enabling efficient tumor accumulation and cytosolic delivery <em>via</em> the enhanced permeability and retention (EPR) effect. Leveraging these favorable properties, MGT-SNPs enhance STING activation both <em>in vitro</em> and <em>in vivo</em>, effectively remodeling TME. Consequently, MGT-SNPs trigger robust anti-tumor immunity in melanoma-bearing mice following either intratumoral or intravenous administration. Collectively, this work showcases a supramolecular self-assembly strategy based on the intrinsic structural properties of a STING agonist for tumor-targeted STING activation, which eliminates carrier-related toxicity and offers a clinically promising approach for STING-targeted cancer immunotherapy.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 9","pages":"Pages 6253-6273"},"PeriodicalIF":14.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148940582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanomaterial-driven spatiotemporal autophagy modulation: The dual-edged sword in precision cancer therapy","authors":"Linghuan Xu,&nbsp;Jintao Hao,&nbsp;Yueyang Zhao,&nbsp;Yanshu Wang,&nbsp;Yuetong Yu,&nbsp;Chaoxing He,&nbsp;Zhiyun Niu,&nbsp;Defang Ouyang,&nbsp;Bai Xiang","doi":"10.1016/j.apsb.2026.06.049","DOIUrl":"10.1016/j.apsb.2026.06.049","url":null,"abstract":"<div><div>Autophagy-modulating nanomaterials have emerged as a promising therapeutic paradigm in oncology, offering precise intervention in tumor progression, metastasis, and treatment resistance. The therapeutic efficacy of these platforms is largely attributed to their context-dependent dual functionality. On one hand, they are capable of inducing cytotoxic autophagy, such as through the activation of oxidative stress or endoplasmic reticulum stress, leading to tumor cell death. On the other hand, they can inhibit cytoprotective autophagy, a crucial survival mechanism exploited by tumor cells, by impairing lysosomal function or perturbing cellular energy metabolism. A key advancement in this field is the ability of nanomaterials to achieve spatiotemporal control over autophagy modulation, allowing targeted regulation at specific tumor sites and disease stages. This review systematically summarizes the molecular mechanisms underlying these bidirectional effects, with particular emphasis on the modulation of selective autophagy pathways including mitophagy, and discusses how rational nanomaterial design adapted to tumor stage and microenvironment dictates therapeutic outcomes. Finally, we highlight major translational challenges, especially the lack of standardized characterization and the difficulty in precisely controlling autophagic responses, which must be addressed to facilitate the clinical translation of these innovative nanotherapeutic strategies.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 9","pages":"Pages 5814-5846"},"PeriodicalIF":14.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148940644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipid nanoparticles as active biointerfaces: From membrane interaction to systemic dysregulation","authors":"Falko Seger,&nbsp;L. Maria Gutschi,&nbsp;Stephanie Seneff","doi":"10.1016/j.apsb.2026.07.001","DOIUrl":"10.1016/j.apsb.2026.07.001","url":null,"abstract":"<div><div>Lipid nanoparticles (LNPs) are central to modern mRNA therapeutics, including COVID-19 vaccines. Far from passive carriers, their ionizable lipids actively interact with cellular membranes. Evidence from cellular, transcriptomic, and proteomic studies indicates that LNPs, with or without nucleic acid, alter gene and protein expression, thereby initiating inflammatory, detoxification, and stress responses at the membrane. Key pathways affected include lipid metabolism and detoxification, with roles for Peroxisome Proliferator-Activated Receptor Gamma (PPAR<em>γ</em>) and cytochrome P450 enzymes. We hypothesize that the phosphatidylinositol (PI) cycle is the primary site of LNP-induced perturbations, regulating membrane restructuring and organelle trafficking during endocytosis. Disruption of this cycle triggers downstream signaling cascades, including nuclear factor kappa B (NF-<em>κ</em>B), mitogen-activated protein kinases (MAPKs), Janus kinase/signal transducers and activators of transcription (JAK/STAT), and mechanistic target of rapamycin (mTOR). We term this systemic effect lipid-nanoparticle-driven membrane dysfunction (L-DMD), characterized by dysregulated cellular communication, stress responses, and energy balance. This review provides a mechanistic framework for understanding the persistent biological effects of modified modRNA-LNP exposure and emphasizes a systems-level intracellular perspective.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 9","pages":"Pages 5674-5708"},"PeriodicalIF":14.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148961157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preclinical evaluation of a novel tetrazine probe within a pretargeted delivery system for theranostics in HER2-positive tumor-bearing mice models","authors":"Pengcheng Ma,&nbsp;Hui Tan,&nbsp;Qingyu Lin,&nbsp;Yuxia Liu,&nbsp;Hua Shen,&nbsp;Shuhua He,&nbsp;Hongxing Su,&nbsp;Zonghua Luo,&nbsp;Dai Shi,&nbsp;Dengfeng Cheng","doi":"10.1016/j.apsb.2026.03.004","DOIUrl":"10.1016/j.apsb.2026.03.004","url":null,"abstract":"<div><div>The approval of radionuclide therapy strategies in nuclear medicine has revolutionized the treatment landscape for patients with advanced malignancies. Due to significant HER2 overexpression in some solid tumors, radionuclide therapy targeting HER2 is a viable strategy. The traditional monoclonal antibody (mAb) direct radiolabelling system may lead to off-target radiation exposure. To address this limitation, we employed the established inverse-electron demand Diels-Alder (IEDDA)-based pretargeting strategy and designed a novel tetrazine probe. First, we identified the optimal targeting molecule (Pertuzumab) and optimal metabolic time (48 h) through micro-positron emission tomography/computed tomography (PET/CT) scans and biodistribution studies of [⁸⁹Zr]Zr-DFO-Per, [⁸⁹Zr]Zr-DFO-Per-F(ab')₂ and [⁸⁹Zr]Zr-DFO-Per-Fab. Next, TCO-Pertuzumab (TCO-Per) was administered to HER2-overexpressing SKOV3 tumor-bearing mice models, and after 48 h of circulation and clearance, a novel radiolabelled small molecule Tz ([¹³¹I]I-Tyr-<span>d</span>-peptide-PEG₁₁-Tz) was introduced. Through a series of <em>in vivo</em> studies, we observed prolonged retention of [¹³¹I]I-Tyr-<span>d</span>-peptide-PEG₁₁-Tz in SKOV3 tumors with rapid renal clearance, along with promising therapeutic efficacy. Our study demonstrates that the novel tetrazine probe within a pretargeting delivery system overcomes limitations of traditional strategies and shows promise for clinical translation.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 8","pages":"Pages 5424-5438"},"PeriodicalIF":14.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13464068/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148719424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mussel-inspired biphasic microneedle patch for long-acting hypothyroidism treatment","authors":"Wen Zhang,&nbsp;Hanqing Liu,&nbsp;Jinxuan Hou,&nbsp;Kai Lei,&nbsp;Jiapeng Lei,&nbsp;Yinli Jin,&nbsp;Chuang Chen,&nbsp;Jianying Huang,&nbsp;Wei Li","doi":"10.1016/j.apsb.2026.04.012","DOIUrl":"10.1016/j.apsb.2026.04.012","url":null,"abstract":"<div><div>Hypothyroidism, caused by insufficient thyroid hormone production or impaired responsiveness, is typically managed with lifelong daily oral levothyroxine sodium (LT₄). However, oral administration often suffers from variable gastrointestinal absorption and poor adherence. Here, we report a mussel-inspired biphasic microneedle (MN) patch integrating LT₄ microcrystals and a bioadhesive PDA-PAM hydrogel backing for sustained and patient-friendly hypothyroidism management. The biphasic MNs, composed of rapidly dissolving PVA/sucrose tips and a robust polystyrene base, efficiently deposit LT₄ microcrystals intradermally upon insertion, enabling gradual dissolution and sustained release. The hydrogel backing offered strong and flexible adhesion, ensuring reliable skin attachment during movement. <em>In vitro</em>, the patches exhibited first-order LT₄ release for 9 days. In hypothyroid rats, a single patch application maintained therapeutic plasma LT₄ concentrations for ∼6 days, with bioavailability comparable to intravenous injection. In a preliminary study in healthy volunteers (<em>n</em>= 13), placebo MN patches demonstrated high insertion efficiency, good short-term tolerability, and favorable user acceptability. While further studies are required to establish long-term safety and efficacy in patients with hypothyroidism, these findings support the feasibility of a minimally invasive, extended-interval LT₄ delivery strategy.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 8","pages":"Pages 5439-5451"},"PeriodicalIF":14.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13464087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148719876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HIFs: The central drivers of tumors and their role as molecular switches in targeted therapy?","authors":"Yi Peng,&nbsp;Ying Che,&nbsp;Yingqi Zhao,&nbsp;Zheng Wang,&nbsp;Zhanlei Pei,&nbsp;Yanyun Hu,&nbsp;Yuhang Yin,&nbsp;Xiaolong Pan,&nbsp;Xiaoyun Hu,&nbsp;Minjie Wei,&nbsp;Huizhe Wu","doi":"10.1016/j.apsb.2026.06.040","DOIUrl":"10.1016/j.apsb.2026.06.040","url":null,"abstract":"<div><div>Hypoxia-inducible factors (HIFs) serve as the central signaling hub within the hypoxic tumor microenvironment, coordinating tumor proliferation, metastasis, and therapy resistance. This protein family comprises HIF-1<em>α</em>, HIF-2<em>α</em>, HIF-3<em>α</em>, and HIF-1<em>β</em>, with distinct subcellular localization patterns reflecting their isoform-specific oxygen-sensing mechanisms. Tumor-associated HIF expression is regulated through a multifaceted network involving non-coding RNAs (ncRNAs), mitochondrial metabolites, and post-translational modifications (PTMs). These aberrantly expressed HIFs then orchestrate biologically important processes including metabolic reprogramming, angiogenesis, and pro-tumorigenic inflammation. It is important to note that current evidence regarding HIF-3<em>α</em> function remains limited and requires further validation <em>in vivo</em>. This review first systematically deciphers the mechanisms governing HIF dysregulation in tumors, before elucidating the key biological processes involved. We then synthesize advances in HIF-targeting inhibitors. These pivotal findings provide a solid theoretical foundation and novel insights for both anticancer therapies targeting this critical “molecular switch” and translational research focusing on HIFs as promising therapeutic targets.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 8","pages":"Pages 4808-4828"},"PeriodicalIF":14.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13464082/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148720075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of non-coding RNAs in regulating R-loop dynamics in cancer: Mechanisms and therapeutic implications","authors":"Sixiang Zheng,&nbsp;Junjie Li,&nbsp;Hong Lin,&nbsp;Xudong Zhang,&nbsp;Fangyi Long,&nbsp;Ting Wang","doi":"10.1016/j.apsb.2026.06.030","DOIUrl":"10.1016/j.apsb.2026.06.030","url":null,"abstract":"<div><div>R-loops, RNA:DNA hybrids formed during transcription, play critical roles in regulating gene expression and maintaining genome stability. Dysregulation of R-loop formation and resolution has been linked to genomic instability, a hallmark of cancer. Recent advances have highlighted the pivotal role of non-coding RNAs (ncRNAs), particularly long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), in modulating R-loop dynamics, influencing tumorigenesis, and contributing to therapeutic resistance. These ncRNAs participate in the formation, stabilization, and resolution of R-loops, which in turn regulate critical processes such as transcriptional regulation, DNA repair, and chromatin architecture. For example, circRNAs such as circSMARCA5 and circDMD have been shown to induce R-loop formation, influencing gene expression and sensitizing cancer cells to chemotherapy. Conversely, lncRNAs such as TUG1 and NEAT1 regulate R-loop resolution, maintaining genome stability and enhancing tumor cell survival. The interaction between ncRNAs and R-loops offers promising avenues for targeted therapeutic strategies aimed at restoring R-loop balance to improve cancer treatment outcomes. This review provides an in-depth exploration of the molecular mechanisms by which ncRNAs modulate R-loop dynamics and discusses their potential as biomarkers and therapeutic targets in oncology. Furthermore, we highlight the challenges and future directions in translating these findings into clinical applications.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 8","pages":"Pages 4749-4769"},"PeriodicalIF":14.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13464092/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148720582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}