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PI3K inhibition to overcome endocrine resistance in breast cancer

Niamh M Keegan1,2, Jack P Gleeson1, Bryan T Hennessy1,2

  • 1a Department of Medical Oncology , Cancer Clinical Trials and Research Unit, Beaumont Hospital , Dublin , Ireland.

Expert Opinion on Investigational Drugs
|December 19, 2017
PubMed
Abstract

Insights

Phosphatidylinositol-3 kinase (PI3K) pathway inhibitors show promise for overcoming endocrine therapy resistance in estrogen receptor-positive breast cancer. PIK3CA mutations may serve as predictive biomarkers for treatment efficacy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • The phosphatidylinositol-3 kinase (PI3K) pathway is crucial in oncogenesis and contributes to treatment resistance in ER-positive and HER2-positive breast cancers.
  • Therapeutic inhibition of the PI3K pathway is an active area of research for breast cancer treatment.

Purpose of the Study:

  • To review key PI3K inhibitors in ER-positive breast cancer.
  • To focus on their role in overcoming endocrine therapy resistance.
  • To explore the potential of PIK3CA mutations as predictive biomarkers.

Main Methods:

  • Review of clinical trial data for PI3K inhibitors.
  • Analysis of preclinical and phase III study findings.
  • Discussion of emerging challenges and novel biomarkers.

Main Results:

  • Several PI3K inhibitors are in clinical trials with variable efficacy and toxicity.
  • PIK3CA mutations are being investigated as predictive biomarkers for PI3K inhibitor response.
  • Endocrine resistance remains a significant challenge in ER-positive breast cancer treatment.

Conclusions:

  • PI3K inhibitors represent a promising strategy to overcome endocrine resistance in ER-positive breast cancer.
  • Further research is needed to optimize PI3K inhibitor selectivity and identify robust predictive biomarkers.
  • Combination therapies may be essential for maximizing treatment efficacy and overcoming resistance.
Keywords:
Breast cancerPI3K inhibitorPIK3CAalpelisibbuparlisibendocrine resistancepictilisibtaselisib

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