A M Gonzalez-Angulo1, G R Blumenschein. 1. Department of Breast Medical Oncology, The University of Texas, M.D. Anderson Cancer Center, Houston, TX, USA. agonzalez@mdanderson.org
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. DESIGN: 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.
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. DESIGN: MEDLINE and international conference abstracts were searched for evidence of markers of sensitivity to PI3K/Akt/mTOR pathway inhibitors in breast cancerpatients 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.
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