Clinical development of mTOR inhibitors in breast cancer

Breast Cancer Res. 2014 Feb 17;16(1):203. doi: 10.1186/bcr3618.

Abstract

The mammalian target of rapamycin (mTOR) pathway is a central pathway that regulates mRNA translation, protein synthesis, glucose metabolism, lipid synthesis and autophagy, and is involved in malignant transformation. Several randomized trials have shown that the use of mTOR inhibitors could improve patient outcome with hormone receptor-positive or human epidermal growth factor receptor-2-positive breast cancer. This review analyzes new perspectives from these trials. Preclinical studies have suggested that the mTOR pathway may play a role in the resistance to hormone therapy, trastuzumab and chemotherapy for breast cancer. This concept has been tested in clinical trials for neoadjuvant treatment and for metastatic breast cancer patients. Also, much effort has gone into the identification of biomarkers that will allow for more precise stratification of patients. Findings from these studies will provide indispensable tools for the design of future clinical trials and identify new perspectives and challenges for researchers and clinicians.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antineoplastic Agents / therapeutic use
  • Everolimus
  • Female
  • Humans
  • Neoadjuvant Therapy
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoinositide-3 Kinase Inhibitors
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • Receptor, ErbB-2 / antagonists & inhibitors*
  • Receptor, ErbB-2 / metabolism
  • Receptors, Estrogen / metabolism
  • Sirolimus / analogs & derivatives
  • Sirolimus / therapeutic use
  • TOR Serine-Threonine Kinases / antagonists & inhibitors*
  • TOR Serine-Threonine Kinases / genetics
  • Trastuzumab
  • Triple Negative Breast Neoplasms / drug therapy*
  • Triple Negative Breast Neoplasms / pathology

Substances

  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Phosphoinositide-3 Kinase Inhibitors
  • Receptors, Estrogen
  • Everolimus
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Proto-Oncogene Proteins c-akt
  • Trastuzumab
  • Sirolimus