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Targeting the PI3K Pathway in Gynecologic Malignancies

Monica Avila1, Michaela Onstad Grinsfelder1, Melissa Pham1

  • 1Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, 1155 Herman Pressler Dr. CPB 6.3279, Houston, TX, 77030, USA.

Current Oncology Reports
|November 19, 2022
PubMed
Abstract

Insights

Aberrant PI3K pathway signaling is common in gynecologic cancers. Targeting this pathway, particularly with mTOR inhibitors like everolimus, shows promise, with biomarkers aiding treatment selection.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • The phosphoinositide 3-kinase (PI3K) signaling pathway plays a crucial role in cell growth, trafficking, and angiogenesis.
  • Aberrations in PI3K signaling are frequently observed in gynecologic malignancies, highlighting its relevance in cancer development.

Purpose of the Study:

  • To review PI3K pathway aberrations in gynecologic cancers.
  • To explore therapeutic targets within the PI3K pathway, especially those successful in endometrial cancers.
  • To identify predictive biomarkers for response to PI3K-targeted therapies.

Main Methods:

  • Review of landmark clinical trials and relevant literature.
  • Analysis of therapeutic strategies targeting the PI3K/mTOR pathway.
  • Discussion of biomarker research for treatment response.

Main Results:

  • Everolimus (an mTOR inhibitor) combined with letrozole showed a 40% clinical benefit rate and 32% objective response rate in endometrial cancers.
  • GOG 3007 trial indicated that everolimus plus letrozole doubled progression-free survival compared to hormonal therapy alone.
  • PI3K pathway alterations are common and present therapeutic opportunities in gynecologic cancers.

Conclusions:

  • The PI3K pathway is a significant target in gynecologic oncology.
  • Targeted therapies, such as mTOR inhibitors, demonstrate efficacy, particularly in endometrial cancer.
  • Biomarker identification is crucial for optimizing patient selection and treatment outcomes.
Keywords:
ActivityCancerCervicalEndometrialGynecologicMalignancyOncologyOvarianPI3KPTENPathwayPhosphoinositide 3-kinaseSignalingUterinemTOR

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