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AKT inhibitors in gynecologic oncology: past, present and future

Jinghong Chen1, Rutie Yin1

  • 1Department of Obstetrics and Gynecology, West China Second University Hospital, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Sichuan University, Chengdu, Sichuan, China.

Frontiers in Oncology
|August 1, 2025
PubMed

Insights

AKT inhibitors show promise in gynecological cancers but face challenges. This review explores recent research to identify biomarkers, overcome resistance, and improve treatment strategies for better clinical outcomes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • The PI3K/AKT/mTOR pathway is crucial in cancer, regulating proliferation, survival, metabolism, and therapy resistance.
  • AKT inhibitors are under development, with several agents in clinical trials, showing variable anti-tumor activity.

Purpose of the Study:

  • To systematically review recent AKT inhibitor (AKTi) research in gynecological cancers.
  • To provide a foundation for identifying biomarkers, overcoming drug resistance, and developing prognostic models for AKTi therapy.

Main Methods:

  • Systematic literature review of recent studies on AKT inhibitors in gynecological cancers.

Main Results:

  • Multiple classes of AKT inhibitors are in development (PH domain competitors, allosteric, ATP-competitive).
  • Early clinical results show encouraging response rates and prolonged progression-free survival (PFS) in select patients.
  • Challenges include confirming efficacy in larger trials, managing toxicities, and elucidating resistance mechanisms.

Conclusions:

  • Further research is needed to optimize AKTi therapy in gynecological cancers.
  • Identifying biomarkers and understanding resistance are key to improving clinical translation.
  • This review provides insights to guide future therapeutic strategies and clinical development.
Keywords:
AKT inhibitorbiomarkerclinical trialgynecological cancertargeted therapy

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