Insights from Clinical Trials on A_2A Adenosine Receptor Antagonists for Cancer Treatment.

IF 4.9 Q1 CHEMISTRY, MEDICINAL

ACS Pharmacology and Translational Science Pub Date : 2025-05-02 eCollection Date: 2025-06-13 DOI:10.1021/acsptsci.5c00057

Pran Kishore Deb, Prasenjit Maity, Biprajit Sarkar, Katharigatta N Venugopala, Rakesh Kumar Tekade, Sanjay Batra

{"title":"Insights from Clinical Trials on A2A Adenosine Receptor Antagonists for Cancer Treatment.","authors":"Pran Kishore Deb, Prasenjit Maity, Biprajit Sarkar, Katharigatta N Venugopala, Rakesh Kumar Tekade, Sanjay Batra","doi":"10.1021/acsptsci.5c00057","DOIUrl":null,"url":null,"abstract":"Accumulation of high concentrations of adenosine (ADO) in the tumor microenvironment represents an important immunosuppressive mechanism that promotes cancer progression through A2A receptor signaling. While initial clinical trials demonstrated modest anticancer effects of monotherapy with A2A receptor antagonists, combination approaches, particularly with immune checkpoint inhibitors, have shown enhanced potential across multiple cancer types. This review examines the therapeutic potential of ADO/A2A receptor modulation in bolstering antitumor immune responses, covering the intricate mechanisms of A2A receptor signaling and ongoing clinical advancements of A2A receptor antagonists and dual A2A/A2B receptor antagonists. Also, we discuss the pivotal role of rational combination strategies in restoring immunocompetence within the tumor microenvironment, thus offering promising prospects for overcoming immune evasion in cancer therapy.","PeriodicalId":36426,"journal":{"name":"ACS Pharmacology and Translational Science","volume":"8 6","pages":"1498-1512"},"PeriodicalIF":4.9000,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12171894/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Pharmacology and Translational Science","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1021/acsptsci.5c00057","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/6/13 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}

引用次数: 0

Abstract

Accumulation of high concentrations of adenosine (ADO) in the tumor microenvironment represents an important immunosuppressive mechanism that promotes cancer progression through A_2A receptor signaling. While initial clinical trials demonstrated modest anticancer effects of monotherapy with A_2A receptor antagonists, combination approaches, particularly with immune checkpoint inhibitors, have shown enhanced potential across multiple cancer types. This review examines the therapeutic potential of ADO/A_2A receptor modulation in bolstering antitumor immune responses, covering the intricate mechanisms of A_2A receptor signaling and ongoing clinical advancements of A_2A receptor antagonists and dual A_2A/A_2B receptor antagonists. Also, we discuss the pivotal role of rational combination strategies in restoring immunocompetence within the tumor microenvironment, thus offering promising prospects for overcoming immune evasion in cancer therapy.

查看原文本刊更多论文

A2A腺苷受体拮抗剂用于癌症治疗的临床研究

肿瘤微环境中高浓度腺苷（ADO）的积累是通过A2A受体信号传导促进癌症进展的重要免疫抑制机制。虽然最初的临床试验表明，A2A受体拮抗剂单药治疗的抗癌效果适度，但联合治疗，特别是与免疫检查点抑制剂联合治疗，已显示出在多种癌症类型中增强的潜力。本文综述了ADO/A2A受体调节在增强抗肿瘤免疫应答中的治疗潜力，涵盖了A2A受体信号传导的复杂机制以及A2A受体拮抗剂和双A2A/A2B受体拮抗剂的临床进展。此外，我们还讨论了合理的组合策略在肿瘤微环境中恢复免疫能力的关键作用，从而为克服癌症治疗中的免疫逃避提供了广阔的前景。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

ACS Pharmacology and Translational Science Medicine-Pharmacology (medical)

CiteScore

10.00

自引率

3.30%

发文量

133

期刊介绍： ACS Pharmacology & Translational Science publishes high quality, innovative, and impactful research across the broad spectrum of biological sciences, covering basic and molecular sciences through to translational preclinical studies. Clinical studies that address novel mechanisms of action, and methodological papers that provide innovation, and advance translation, will also be considered. We give priority to studies that fully integrate basic pharmacological and/or biochemical findings into physiological processes that have translational potential in a broad range of biomedical disciplines. Therefore, studies that employ a complementary blend of in vitro and in vivo systems are of particular interest to the journal. Nonetheless, all innovative and impactful research that has an articulated translational relevance will be considered. ACS Pharmacology & Translational Science does not publish research on biological extracts that have unknown concentration or unknown chemical composition. Authors are encouraged to use the pre-submission inquiry mechanism to ensure relevance and appropriateness of research.