title: Role of mTOR inhibition in preventing resistance and restoring sensitivity to hormone-targeted and HER2-targeted therapies in breast cancer.
abstract: Even with hormone-targeted and human epidermal growth factor receptor 2 (HER2)-targeted anticancer agents, intrinsic resistance or acquired resistance are common occurrences in estrogen receptor-positive and HER2-positive breast cancers, respectively. Potential mechanisms for resistance to targeted agents include steric inhibition imposed by other cellular elements, molecular changes in the target receptor, alterations in the regulation of downstream signaling components, compensatory cross-talk with other signaling pathways, and pharmacogenetic alterations in the host. Evidence suggests that both hormone receptor-positive tumors and HER2-overexpressing tumors use the phosphoinositide 3-kinase/Akt/ mammalian target of rapamycin (mTOR) pathway to escape control of antihormone and anti-HER2 therapies. The combination of mTOR inhibitors with hormone-targeted or HER2-targeted therapies appears to be a promising strategy for overcoming resistant disease and preventing the development of resistance.
authors.affiliation: Vanderbilt University School of Medicine/Vanderbilt-Ingram Cancer Center, Nashville, TN 37232, USA.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Mayer
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D002986:Clinical Trials as Topic; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D018931:Antineoplastic Agents, Hormonal; D019869:Phosphatidylinositol 3-Kinases; D047428:Protein Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D018719:Erb-b2 Receptor Tyrosine Kinases; D058570:TOR Serine-Threonine Kinases