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Defining biomarkers to predict sensitivity to PI3K/Akt/mTOR pathway inhibitors in breast cancer

A M Gonzalez-Angulo1, G R Blumenschein

  • 1Department of Breast Medical Oncology, The University of Texas, M.D. Anderson Cancer Center, Houston, TX, USA. agonzalez@mdanderson.org

Cancer Treatment Reviews
|December 11, 2012
PubMed
Abstract

Insights

Identifying biomarkers for phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway inhibitors in breast cancer is crucial. Current evidence suggests PI3K pathway aberrations may predict response, but more research is needed to identify all sensitive patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Biomarker identification and validation are critical for targeted cancer therapy.
  • The PI3K/Akt/mTOR pathway is a key therapeutic target in breast cancer.
  • Developing biomarkers to select patients for PI3K/Akt/mTOR inhibitors is an unmet need.

Purpose of the Study:

  • To review evidence for biomarkers predicting sensitivity to PI3K/Akt/mTOR pathway inhibitors in breast cancer.
  • To assess the current state of biomarker validation in preclinical and clinical settings.

Main Methods:

  • A systematic search of MEDLINE and international conference abstracts was conducted.
  • Evidence was gathered on markers of sensitivity in both preclinical models and breast cancer patients.

Main Results:

  • Preclinical data indicate PI3K/Akt/mTOR pathway aberrations, particularly in PIK3CA, may identify responsive breast cancer patients.
  • Additional biomarkers are required to identify all patients with inherent sensitivity.
  • Early clinical validation studies for these biomarkers have yielded inconclusive results.

Conclusions:

  • Prospective, well-designed clinical trials are essential to validate candidate biomarkers for PI3K/Akt/mTOR inhibitors in breast cancer.
  • Further research should determine the optimal PI3K/Akt/mTOR inhibitor for different molecular subtypes based on specific alterations.

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