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FOXO factors and breast cancer: outfoxing endocrine resistance

M Bullock1

  • 1Hormones and Cancer GroupCancer Genetics Laboratory, Kolling Institute of Medical Research, Royal North Shore Hospital, Pacific Highway Saint Leonards, Sydney, New South Wales 2065, Australia martyn.bullock@sydney.edu.au.

Endocrine-Related Cancer
|November 28, 2015
PubMed

Insights

Estrogen receptor-positive breast cancers often develop endocrine resistance. This review explores how the PI3K-AKT-forkhead box O (FOXO) pathway contributes to resistance and suggests therapies to restore FOXO function.

Area of Science:

  • Oncology
  • Molecular Biology
  • Endocrinology

Background:

  • Metastatic breast cancer is a significant global health issue, with most cases incurable.
  • Estrogen receptor-positive breast cancers (approximately 70%) benefit from endocrine therapy, but resistance is common.
  • Understanding hormone sensitivity is crucial for improving endocrine therapy efficacy.

Purpose of the Study:

  • To review the role of the PI3K-AKT-forkhead box O (FOXO) signaling axis in endocrine resistance mechanisms of breast cancer.
  • To explore how PI3K-AKT pathway activation impacts FOXO tumor suppressor functions.
  • To propose potential therapeutic strategies for restoring normal FOXO transcriptional activity.

Main Methods:

  • Literature review of current research on FOXO signaling in breast cancer.
  • Analysis of molecular pathways involved in endocrine resistance.
  • Synthesis of information on therapeutic interventions targeting FOXO.

Main Results:

  • The PI3K-AKT-FOXO signaling axis is implicated in hormone-independent breast cancer growth.
  • Constitutive activation of the PI3K-AKT pathway leads to decreased FOXO tumor suppressor activity.
  • FOXO dysfunction is a key factor in the development of endocrine resistance.

Conclusions:

  • Restoring normal FOXO transcriptional activity may overcome endocrine resistance.
  • Targeting the PI3K-AKT-FOXO pathway offers potential therapeutic avenues for metastatic breast cancer.
  • Further research into FOXO-mediated mechanisms is essential for advancing breast cancer treatment.
Keywords:
FOXOsPI3K–AKT pathwaybreast cancerendocrine resistancepost-translational modifications

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