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Potential of overcoming resistance to HER2-targeted therapies through the PI3K/Akt/mTOR pathway

Sharon T Wilks1

  • 1Cancer Care Centers of South Texas, US Oncology, San Antonio, TX 78229, USA.

Breast (Edinburgh, Scotland)
|July 19, 2015
PubMed

Insights

Resistance to HER2-targeted therapies in breast cancer is a significant challenge. Understanding molecular mechanisms, like PI3K/Akt/mTOR pathway activation, is key to developing new strategies to overcome treatment resistance.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Human epidermal growth factor receptor 2 (HER2) overexpression is common in aggressive breast cancers.
  • HER2-targeted therapies improve outcomes but resistance frequently develops.
  • Identifying resistance mechanisms is crucial for improving patient prognosis.

Purpose of the Study:

  • To review molecular mechanisms of resistance to HER2-targeted therapies.
  • To evaluate strategies for managing resistance in HER2-positive breast cancer.
  • To explore the role of the PI3K/Akt/mTOR pathway in treatment resistance.

Main Methods:

  • Literature review of molecular mechanisms of resistance.
  • Evaluation of clinical trial data for resistance-targeting agents.
  • Analysis of signaling pathways implicated in HER2 therapy resistance.

Main Results:

  • Activation of the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway is implicated in resistance.
  • Inhibitors of the PI3K/Akt/mTOR pathway show promise in overcoming resistance.
  • Phase 3 data suggest efficacy of everolimus in combination therapies for refractory disease.

Conclusions:

  • Understanding resistance mechanisms is vital for advancing HER2-positive breast cancer treatment.
  • Targeting the PI3K/Akt/mTOR pathway represents a promising strategy to overcome resistance.
  • Combination therapies including PI3K/Akt/mTOR inhibitors may improve outcomes for patients with refractory disease.
Keywords:
Breast cancerEverolimusHER2ResistancemTOR

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