REVIEW article
Front. Oncol.
Sec. Gynecological Oncology
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1547083
AKT inhibitors in gynecologic oncology: past, present and future
Provisionally accepted
Jinghong Chen
Rutie Yin Chen*- Key Laboratory of Birth Defects and Related Diseases of Women and Children, West China Second University Hospital, Sichuan University, Chengdu, China
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The PI3K/AKT/mTOR pathway serves as a critical signaling nexus in cancer, with AKT acting as a central regulator of tumor cell proliferation, survival, metabolism, and therapy resistance. AKT inhibitors show promising but variable anti-tumor activity in preclinical and clinical studies. Currently, multiple classes of AKT inhibitors-PH domain competitors (perifosine), allosteric inhibitors (MK-2206), and ATP-competitive agents (AZD5363, GSK2110183, GSK2141795, and GDC-0068) are under development, with several agents in phase II/III trials. While early results demonstrated encouraging response rates and prolonged PFS in selected patients, significant challenges remain. The efficacy needs confirmation in larger trials, toxicities require better management, and resistance mechanisms demand further elucidation to guide optimal therapeutic strategies. This study systematically reviews recent AKTi research in gynecological cancers, aiming to provide a theoretical foundation for identifying potential biomarkers, overcoming drug resistance, and developing prognostic models.These insights may further facilitate the clinical translation of key therapeutic agents.
Keywords: Akt inhibitor, gynecological cancer, targeted therapy, biomarker, Clinical Trial
Received: 17 Dec 2024; Accepted: 26 Jun 2025.
Copyright: © 2025 Chen and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Rutie Yin Chen, Key Laboratory of Birth Defects and Related Diseases of Women and Children, West China Second University Hospital, Sichuan University, Chengdu, China
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