Expert Opinion on Therapeutic Targets最新文献_第4页

The PDPK1-RSK2 axis as a potential convergent therapeutic vulnerability in B-cell lymphomas. PDPK1-RSK2轴作为b细胞淋巴瘤的潜在会聚治疗易感性。

IF 5.1 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2026-08-01 Epub Date: 2026-07-25 DOI: 10.1080/14728222.2026.2709802

Junya Kuroda, Taku Tsukamoto, Yuji Shimura

{"title":"The PDPK1-RSK2 axis as a potential convergent therapeutic vulnerability in B-cell lymphomas.","authors":"Junya Kuroda, Taku Tsukamoto, Yuji Shimura","doi":"10.1080/14728222.2026.2709802","DOIUrl":"10.1080/14728222.2026.2709802","url":null,"abstract":"Introduction: B-cell lymphomas (BCLs) are the most prevalent group of hematologic cancers, encompassing various subtypes, each with a distinct clinical course shaped by cell of origin, genetics, and etiology. Recent advances in subtype-specific immunochemotherapy, targeted therapies, and cellular immunotherapy have improved outcomes for BCLs; nonetheless, some cases remain resistant to existing treatments. To address these resistant disease states, especially across multiple subtypes, the development of new universal targeted therapies could be transformative.Areas covered: This review first highlights what distinguishes the PDPK1/RSK2 signaling axis, outlines its normal biological functions, and briefly examines its roles in solid tumors. It then narrows the focus to BCLs, supported by evidence from our research on pathway activation, functional dependence, prognostic value, and early-stage drug development.Expert opinion: The PDPK1/RSK2 axis is activated in nearly all BCL subtypes and likely plays a significant role in disease development. This suggests the potential for treatments that work across subtypes, despite their genetic and phenotypic differences. Targeting a shared signaling pathway might help overcome resistance seen with traditional precision medicine and support the development of new therapies for rare disease subtypes. However, because current research remains preclinical, more work is necessary.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"873-883"},"PeriodicalIF":5.1,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148561196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 therapy-induced senescence-associated secretory phenotype and epithelial-mesenchymal transition axis in ovarian cancer: molecular mechanisms and therapeutic opportunities. 卵巢癌治疗诱导的衰老相关分泌表型和上皮-间质转化轴：分子机制和治疗机会。

IF 5.1 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2026-08-01 Epub Date: 2026-07-30 DOI: 10.1080/14728222.2026.2709798

Ruiqi Wang, Dongsheng Shang, Zhigang Tu, Hanqing Liu

{"title":"The therapy-induced senescence-associated secretory phenotype and epithelial-mesenchymal transition axis in ovarian cancer: molecular mechanisms and therapeutic opportunities.","authors":"Ruiqi Wang, Dongsheng Shang, Zhigang Tu, Hanqing Liu","doi":"10.1080/14728222.2026.2709798","DOIUrl":"10.1080/14728222.2026.2709798","url":null,"abstract":"Introduction: Therapy-induced senescence (TIS) is an important response to anticancer treatments in ovarian cancer, which can trigger the senescence-associated secretory phenotype (SASP) that may contribute to epithelial-mesenchymal transition (EMT), tumor migration, invasion, and adhesion. This review delineates the molecular mechanisms through linking TIS-mediated SASP to EMT and evaluates emerging therapeutic opportunities.Areas covered: We discuss key regulatory pathways including cGAS-STING, NF-κB, p53, and STAT3 that orchestrate SASP components such as IL-6, IL-8, and TGF-β to activate EMT transcription factors. Bioinformatics analyses of clinical datasets identify SASP factors (IL-6, AREG, c-JUN, TIMP1, THBS1) as critical EMT mediators, with hub genes including COL4A2, COL5A2, PDGFRB, and FBN1 involved in ECM remodeling and cell adhesion. SASP promotes ovarian cancer cell adhesion through MMP-mediated ECM degradation, release of matrix-bound growth factors, generation of adhesive fragments, and induction of mesothelial-mesenchymal transition. We evaluate emerging therapeutic strategies targeting this axis, including senolytics to eliminate senescent cells, senomorphics to suppress SASP secretion, and targeted inhibition of specific SASP components.Expert opinion: Although preclinical advances are promising, challenges in model systems and real-time SASP monitoring remain; future integrated multi-omics analyses and personalized therapeutic approaches are needed to translate these findings into improved ovarian cancer outcomes.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"885-902"},"PeriodicalIF":5.1,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148619025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Molecular insights for targeting the Nrf1 pathway in hepatocellular carcinoma. 靶向Nrf1通路在肝细胞癌中的分子研究。

IF 5.1 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2026-07-01 Epub Date: 2026-06-29 DOI: 10.1080/14728222.2026.2695709

Xi Chen, Zhengwen Zhang, Siqian Cui, Yiguo Zhang

{"title":"Molecular insights for targeting the Nrf1 pathway in hepatocellular carcinoma.","authors":"Xi Chen, Zhengwen Zhang, Siqian Cui, Yiguo Zhang","doi":"10.1080/14728222.2026.2695709","DOIUrl":"10.1080/14728222.2026.2695709","url":null,"abstract":"Introduction: Nuclear factor erythroid 2-related factor 1 (Nrf1, encoded by NFE2L1) plays a central role in maintaining cellular homeostasis, basal redox balance, and mitochondrial quality control and its function. Recent studies have revealed that Nrf1 assumes complex, even opposing, roles in functioning both as a tumor-suppressor and otherwise, also as an unconvincing driver of Hepatocellular carcinoma (HCC) progression through certain oncogenic pathways and redox stress adaptation.Areas covered: This mini-review systematically outlines the molecular-cellular regulatory network of Nrf1 and further elucidates its functional divergence and synergy with Nrf2 (encoded by NFE2L2) in HCC.Expert opinion: Research on Nrf1 in the field of HCC has evolved from describing its basic pathophysiological functions to a systematic analysis of its putative dual roles in tumor initiation and progression, its isoform specificity, complex regulatory networks, and therapeutic potentials. Targeting Nrf1 for hepatocellular carcinoma therapy is just facing multiple challenges. Future research priorities will focus on elucidating Nrf1 isoform specificity and post-translational modification profiles, developing a molecular classification system based on the Yin (Nrf1)-Yang (Nrf2) balance, and even non-equilibrium steady-states, and screening for Nrf1α/TCF11-targeting modulators or activators to stimulate homeostatic anti-cancer defense mechanisms.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"693-706"},"PeriodicalIF":5.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148316406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Possibility to therapeutically exploit RGPR-p117 as a target in cancer cells. 利用RGPR-p117作为癌细胞靶点进行治疗的可能性。

IF 5.1 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2026-07-01 Epub Date: 2026-07-19 DOI: 10.1080/14728222.2026.2706466

Masayoshi Yamaguchi

{"title":"Possibility to therapeutically exploit RGPR-p117 as a target in cancer cells.","authors":"Masayoshi Yamaguchi","doi":"10.1080/14728222.2026.2706466","DOIUrl":"10.1080/14728222.2026.2706466","url":null,"abstract":"Introduction: RGPR-p117 was identified as a transcription factor that binds to the TTGGC(N)6CC sequence in the promoter region of the regucalcin gene, a tumor suppressor. This article discusses the therapeutic potential of targeting RGPR-p117 in cancer cells.Area covered: The cytoplasmic RGPR-p117 moves into the nucleus of cells. Once there, it enhances the transcription of several genes containing a TTGGC motif. Overexpression of RGPR-p117 suppresses the proliferation of cancerous cells and decreases the expression levels of proteins that promote their growth, such as Ras, PI3K, Akt, MAPK, and mTOR. It increases the tumor suppressors p53, Rb, and p21. RGPR-p117 also enhances the regucalcin gene expression, which can prevent and treat carcinogenesis. Increasing RGPR-p117 transcription activity may be a promising approach for gene therapy in cancer cells.Expert opinion: Developing novel therapeutic agents that target the RGPR-p117 gene and applying gene therapy are significant and novel cancer treatment strategies. Targeting the RGPR-p117 nuclear translocation pathway may be a new way to suppress cancer. RGPR-p117 shows promise as an effective cancer therapy. However, all of these findings are from in vitro studies. Further in vivo studies and clinical trials are needed, as are solutions to problems, including cancer burden and the need for new targets.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"641-645"},"PeriodicalIF":5.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148469780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

APE1/Ref-1: multifunctional biology, selective inhibition, and the path to clinical translation. APE1/Ref-1：多功能生物学、选择性抑制和临床转化途径。

IF 5.1 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2026-07-01 Epub Date: 2026-07-21 DOI: 10.1080/14728222.2026.2706465

Jessica A Occhiuto, Silpa Gampala, Melissa L Fishel, Mark R Kelley

{"title":"APE1/Ref-1: multifunctional biology, selective inhibition, and the path to clinical translation.","authors":"Jessica A Occhiuto, Silpa Gampala, Melissa L Fishel, Mark R Kelley","doi":"10.1080/14728222.2026.2706465","DOIUrl":"10.1080/14728222.2026.2706465","url":null,"abstract":"Introduction: Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) is a multifunctional stress-response regulator that coordinates genome maintenance, redox signaling, RNA biology, and cellular metabolism. Its expression and subcellular localization further determine disease states and severity. The growing appreciation of its biological complexity and clinical relevance makes APE1/Ref-1 an increasingly attractive therapeutic target for redox-stress-related diseases.Areas covered: In this review, we aim to consolidate information on the structural and mechanistic basis of APE1/Ref-1 redox and repair functions, while recognizing emerging evidence in DNA/RNA-forming G-quadruplex (rG4) biology, RNA metabolism, protein homeostasis, and mitochondrial function. We discuss mechanisms regulating APE1/Ref-1 expression, activity, and trafficking, which dynamically influence function in physiological and disease contexts. We specifically emphasize therapeutic strategies including redox-specific inhibition, endonuclease-targeted approaches, and genetic perturbations that result in distinct effects across disease models.Expert opinion: Evolving understanding of APE1/Ref-1 biology has accelerated therapeutic development, particularly through redox-selective targeting strategies. Small-molecule inhibitors such as APX3330 and new-generation analogs like APX2009 and APX2014 have advanced into therapeutic applications spanning cancer, inflammatory disorders, and ocular diseases. Continued investigation into the context-dependent and multifunctional roles of APE1/Ref-1, together with the progression of mechanism-informed therapeutic design, is steadily strengthening the translational potential of APE1/Ref-1-directed therapies.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"659-674"},"PeriodicalIF":5.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13451991/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148548242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Tailored strategies to overcome third-generation TKI resistance in EGFR-mutated non-small cell lung cancer. 在egfr突变的非小细胞肺癌中克服第三代TKI耐药的定制策略

IF 5.1 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2026-07-01 Epub Date: 2026-07-22 DOI: 10.1080/14728222.2026.2706458

Isabella Saporita, Giovanni Farinea, Elisa Lombardi, Paolo Bironzo, Silvia Novello, Francesco Passiglia

{"title":"Tailored strategies to overcome third-generation TKI resistance in EGFR-mutated non-small cell lung cancer.","authors":"Isabella Saporita, Giovanni Farinea, Elisa Lombardi, Paolo Bironzo, Silvia Novello, Francesco Passiglia","doi":"10.1080/14728222.2026.2706458","DOIUrl":"10.1080/14728222.2026.2706458","url":null,"abstract":"Introduction: In the era of precision medicine, targeting resistance mechanisms is a rational approach to optimize treatment management based on tumor molecular profiling, with the goal of improving clinical outcomes. However, the role of tailored strategies in the treatment algorithm of EGFR-mutated NSCLC remains incompletely defined.Areas covered: This review provides an overview of resistance mechanisms to EGFR-targeted therapy. Acquired resistances include on-target alterations (EGFR C797S and other secondary kinase domain mutations), off-target pathways activation (MET or HER2 amplification, RAS-MAPK, oncogenic fusions), and neuroendocrine transformation to SCLC. Evidence from clinical and observational studies demonstrates activity of tailored therapies, such as EGFR plus MET inhibitors combinations. In parallel, mechanism-agnostic strategies, including bispecific antibodies and ADC have emerged as effective options in the post-osimertinib setting.Expert opinion: Comprehensive molecular assessment through both tissue and liquid biopsy at EGFR-TKI progression is essential to identify actionable alterations and guide treatment decisions. When supported by Molecular Tumor Board discussion, biomarker-driven strategies could enable personalized treatment selection and provide effective chemotherapy-free options. Emergence of upfront combinations is reshaping the biological landscape of EGFR-TKI resistance, increasing the proportion of patients with unknown escape mechanisms and potentially affecting the feasibility of molecularly matched therapies in later lines.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"675-691"},"PeriodicalIF":5.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148520365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Fibroblast activation protein inhibitor-based theranostics in neuroendocrine neoplasms. 基于成纤维细胞活化蛋白抑制剂的神经内分泌肿瘤治疗。

IF 5.1 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2026-07-01 Epub Date: 2026-07-20 DOI: 10.1080/14728222.2026.2706456

Anna La Salvia, Daniela Lucente, Stefania Bellino

引用次数: 0

The role of bile acid receptors in cholestatic liver disease: pathophysiological insights and therapeutic advances. 胆汁酸受体在胆汁淤积性肝病中的作用：病理生理学见解和治疗进展。

IF 5.1 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2026-07-01 Epub Date: 2026-07-04 DOI: 10.1080/14728222.2026.2695704

Hongying Zhou, Jie Yang, Wenbin Wu, Shizhang Wei, Yanling Zhao, Chunyu Li

{"title":"The role of bile acid receptors in cholestatic liver disease: pathophysiological insights and therapeutic advances.","authors":"Hongying Zhou, Jie Yang, Wenbin Wu, Shizhang Wei, Yanling Zhao, Chunyu Li","doi":"10.1080/14728222.2026.2695704","DOIUrl":"10.1080/14728222.2026.2695704","url":null,"abstract":"Introduction: Cholestatic liver disease (CLD) is a group of hepatobiliary disorders characterized by impaired bile flow, leading to the accumulation of toxic bile acids (BAs) and progressive liver injury. The available pharmacotherapies are limited and often inadequate.Areas covered: This review explores the therapeutic potential of BA-activated receptors, encompassing nuclear receptors and membrane-bound G protein-coupled receptors, in the context of CLD. A comprehensive search of the relevant literature was conducted by means of targeted searches of recent peer-reviewed studies focusing on preclinical and clinical studies of BA receptor modulators. The present study transcends a mere descriptive catalog, instead providing a balanced assessment of key signaling cascades. Moreover, the text undertakes a critical discussion of translational failures and safety concerns. The present study focuses on the examination of emerging therapeutic classes and experimental natural products, with particular emphasis on clinical feasibility and limitations.Expert opinion: The failure of pan-FXR agonists signals a need for a paradigm shift. The present study puts forward a novel framework for the development of context-dependent, isoform-selective modulators. It is anticipated that a shift from pan‑FXR agonism to pathway‑selective modulation will occur within a five-year timeframe.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"707-719"},"PeriodicalIF":5.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148316385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

5-FU in combination with PARP inhibitor ABT-888 deregulates MGMT-dependent mismatch repair (MMR) pathway in MMR-proficient colorectal cancer stem cells by modulating MGMT/PARP1/MSH6 complex. 5-FU联合PARP抑制剂ABT-888通过调节MGMT/PARP1/MSH6复合物，解除MMR精通的结直肠癌干细胞中MGMT依赖的错配修复（MMR）途径。

IF 5.1 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2026-07-01 Epub Date: 2026-07-23 DOI: 10.1080/14728222.2026.2706483

Subarno Paul, Chinmay Das, Subhasmita Bhal, Saptarshi Sinha, Somya Ranjan Dash, Sushree Subhadra Acharya, Aakash Goswami, Kunal Goutam, Chanakya Nath Kundu, Tithi Parija

{"title":"5-FU in combination with PARP inhibitor ABT-888 deregulates MGMT-dependent mismatch repair (MMR) pathway in MMR-proficient colorectal cancer stem cells by modulating MGMT/PARP1/MSH6 complex.","authors":"Subarno Paul, Chinmay Das, Subhasmita Bhal, Saptarshi Sinha, Somya Ranjan Dash, Sushree Subhadra Acharya, Aakash Goswami, Kunal Goutam, Chanakya Nath Kundu, Tithi Parija","doi":"10.1080/14728222.2026.2706483","DOIUrl":"10.1080/14728222.2026.2706483","url":null,"abstract":"Background: Previous study showed the PARP inhibitor ABT-888 potentiates the cytotoxicity of 5-fluorouracil (5-FU) by inhibiting PARP1-mediated mismatch repair (MMR) pathway via MSH6 deregulation in MMR-proficient colorectal cancer stem cells (CRC-CSCs). Emerging evidence indicates 5-FU regulates O6 -methylguanine-DNA-methyltransferase (MGMT) activity, but the mechanistic basis of MGMT involvement in PARP1-mediated MMR pathway following 5-FU treatment remains complex and poorly defined.Research design and methods: This study delineates the role of MGMT in 5-FU-induced MMR pathway activation and evaluates 5-FU+ABT-888 combination effects on MGMT modulation in CRC-CSCs. The molecular mechanism has been studied by using colocalization, western blot, co-immunoprecipitation, MGMT gene-knockdown, and molecular docking in in vitro, in silico, and ex vivo preclinical models.Results: 5-FU treatment induced PARylated-PARP1 in CRC-CSCs, promoting PARP1-MGMT-MSH6 interactions that activated MMR. ABT-888 inhibited PARylation in 5-FU-pre-exposed CSCs. Therefore, PARP1 could not physically interact with both MGMT and MSH6, and complete abolishment of MGMT and MSH6, and MMR protein downregulation were observed in combination treatment. MGMT silencing confirmed its critical role in PARP1-mediated MMR activation. Similar findings were obtained in in silico and ex vivo models.Conclusions: 5-FU+ABT-888 enhanced CRC-CSCs death by inhibiting the PARP1-MGMT-MSH6 interaction and simultaneously inhibiting the MGMT-dependent PARP1-mediated MMR pathway in MMR-proficient CRC-CSCs.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"785-802"},"PeriodicalIF":5.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148469762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Transient receptor potential (TRP) channels: an emerging therapeutic target for the treatment of cardiac hypertrophy. 瞬时受体电位（TRP）通道：治疗心肌肥厚的新靶点。

IF 5.1 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2026-07-01 Epub Date: 2026-06-26 DOI: 10.1080/14728222.2026.2691873

Saumya Upadhyay, Shyam Sunder Sharma

{"title":"Transient receptor potential (TRP) channels: an emerging therapeutic target for the treatment of cardiac hypertrophy.","authors":"Saumya Upadhyay, Shyam Sunder Sharma","doi":"10.1080/14728222.2026.2691873","DOIUrl":"10.1080/14728222.2026.2691873","url":null,"abstract":"Introduction: Cardiac hypertrophy (CH) is a major contributor to cardiovascular disease (CVD), affecting millions worldwide. While initially an adaptive response, sustained hypertrophic stimuli lead to maladaptive outcomes, including heart failure (HF), contractile dysfunction, and ventricular remodeling. Key pathophysiological processes involve myocardial fibrosis, cardiomyocyte death, mitochondrial impairment and Ca2+ dysregulation. Despite available therapies, treatment of CH is symptomatic with no approved targeted options. Many interventions have only temporary benefits, may cause adverse hemodynamic effects, and involve procedural risks.Areas covered: This review highlights TRP channels as emerging therapeutic targets in CH. TRP channels play pivotal roles in calcium (Ca2+) homeostasis and modulate apoptosis, cell proliferation, hypoxia adaptation, inflammation, and metabolic reprogramming, core drivers of cardiac remodeling. Pharmacological modulation of TRP activity may counter pathological hypertrophy by tuning hypertrophic signaling, mitigating fibrosis, and enhancing cardiac performance. Incorporating TRP-targeted strategies into treatment paradigms could help address the limitations of current therapies.Expert opinion: We propose that TRP channel-based interventions with mechanistic insights, hold significant promise for precision management of CH. Many TRP subtypes remain uncharacterized, and their investigation could reveal new therapeutic aspects. Future research should prioritize mapping TRP-mediated pathways and validating their translational potential.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"721-756"},"PeriodicalIF":5.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148270754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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