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mTOR inhibitors in the treatment of breast cancer

Shaveta Vinayak1, Robert W Carlson

  • 1Department of Medicine, Stanford University School of Medicine, Stanford, California 94035-5826, USA.

Oncology (Williston Park, N.Y.)
|March 7, 2013
PubMed

Insights

The PI3K/mTOR pathway is often dysregulated in breast cancer, leading to resistance to treatments. Combining mTOR inhibitors with endocrine therapy shows promise in overcoming this resistance, particularly in metastatic hormone receptor-positive breast cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • The phosphatidylinositol 3-kinase/mammalian target of rapamycin (PI3K/mTOR) pathway is frequently dysregulated in breast cancer.
  • Pathway hyperactivation is associated with resistance to endocrine therapy and trastuzumab (Herceptin).

Purpose of the Study:

  • To review preclinical and clinical studies of mTOR inhibitors in breast cancer.
  • To summarize results from ongoing clinical trials involving mTOR or dual PI3K/mTOR inhibitors.

Main Methods:

  • Review of preclinical studies investigating PI3K pathway hyperactivation and treatment resistance.
  • Analysis of clinical trial data for combination therapies of mTOR inhibitors with endocrine agents or anti-HER2 therapies.

Main Results:

  • Combination therapy with everolimus (Afinitor) and tamoxifen or exemestane (Aromasin) demonstrated improved efficacy over endocrine therapy alone in metastatic hormone receptor-positive breast cancer.
  • Early clinical data for PI3K/mTOR inhibitors combined with anti-HER2 therapies in HER2-positive breast cancer are encouraging.

Conclusions:

  • Targeting the PI3K/mTOR pathway, particularly with mTOR inhibitors in combination regimens, offers a promising strategy to overcome endocrine resistance in breast cancer.
  • Identifying biomarkers for response and resistance to mTOR inhibitors is crucial for optimizing treatment selection.

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