title: Defining biomarkers to predict sensitivity to PI3K/Akt/mTOR pathway inhibitors in breast cancer.
abstract: BACKGROUND
  Identification and validation of biomarkers is increasingly important for the integration of novel targeted agents in the treatment of cancer. The phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway represents a promising therapeutic target in breast carcinoma, and inhibitors targeting different nodes of the PI3K/Akt/mTOR axis are in development. Identification of biomarkers to help select patients who are most likely to benefit from these treatments is an essential unmet need.
  
  
  METHODS
  MEDLINE and international conference abstracts were searched for evidence of markers of sensitivity to PI3K/Akt/mTOR pathway inhibitors in breast cancer patients and preclinical models.
  
  
  RESULTS
  Preclinical evidence suggests that PI3K/Akt/mTOR pathway aberrations, notably in PIK3CA, may identify a subpopulation of patients with breast cancer who preferentially respond to PI3K/Akt/mTOR inhibitors. However, additional markers are needed to identify all patients with de novo sensitivity to PI3K/Akt/mTOR pathway inhibition. Early clinical studies to validate these biomarkers have as yet been inconclusive.
  
  
  CONCLUSIONS
  Prospective, adequately designed and powered clinical trials are needed to test candidate biomarkers of sensitivity to PI3K/Akt/mTOR pathway inhibitors in patients with breast cancer, and to determine whether certain PI3K/Akt/mTOR pathway inhibitors are more appropriate in different subtypes depending on the pattern of molecular alteration.
authors.affiliation: Department of Breast Medical Oncology, The University of Texas, M.D. Anderson Cancer Center, Houston, TX, USA. agonzalez@mdanderson.org
authors.forename: A M
authors.initials: AM
authors.lastname: Gonzalez-Angulo
authors.forename: G R
authors.initials: GR
authors.lastname: Blumenschein
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology*; D002986:Clinical Trials as Topic; D005260:Female; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods; D051058:Oncogene Protein v-akt / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D051058:Oncogene Protein v-akt; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D058570:TOR Serine-Threonine Kinases; C546842:MTOR protein, human