title: Overcoming endocrine resistance in breast cancer: role of the PI3K and the mTOR pathways.
abstract: Overcoming endocrine resistance is a 21st century hurdle in the treatment of hormone receptor-positive breast cancers. Estrogen plays a role in the growth of 70% of breast cancers. There are many strategies evolved to overcome estrogen resistance. Established strategies include using drugs such as tamoxifen, a selective estrogen receptor modulator to selectively block estrogen receptors and aromatase inhibitors to decrease the synthesis of estrogen. However, endocrine resistance is commonly encountered in treating patients with standard single-therapy regimens. Recently, the role of the PI3K and the mTOR pathways has been targeted to overcome resistance. The mTOR pathway is a complex pathway regulating cell metabolism, growth and apoptosis. Novel agents such as mTOR inhibitors, PI3K inhibitors and Akt inhibitors are transitioning from bench-top research to clinical application with promising results. This article reviews the common mechanisms of endocrine resistance, and combination therapies that utilize the mTOR/PI3K pathways to overcome resistance.
authors: Section of Hematology/Oncology Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, WV 26506-9162, USA.
authors: Aaron
authors: A
authors: Provenzano
authors: Sobha
authors: S
authors: Kurian
authors: Jame
authors: J
authors: Abraham
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols; D047072:Aromatase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005260:Female; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013629:Tamoxifen / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D019869:Phosphatidylinositol 3-Kinases; D020845:Selective Estrogen Receptor Modulators; D058570:TOR Serine-Threonine Kinases; D013629:Tamoxifen; C546842:MTOR protein, human