Does the PI3K pathway play a role in basal breast cancer?
Many cell kinases exert their proliferative and pro-survival effects through activation of the phosphatidylinositol 3-kinase (PI3K)-Akt pathway. Basal-like breast cancer is a subtype that can be identified by molecular analysis and often includes tumors lacking expression of estrogen receptor/progesterone receptor or human epidermal growth factor receptor, also known as triple-negative breast cancers. Triple-negative cancers comprise < 20% of all breast cancers and have no obvious mechanism driving proliferation, yet these tumors demonstrate higher levels of Akt activation compared with non-triple-negative breast cancers. This suggests a possible role for targeting the PI3K pathway for the treatment of this subset of aggressive cancers. Most clinical trials which have attempted targeting the PI3K/Akt pathway in triple-negative breast cancer have involved the use of EGFR inhibitors with limited success. Novel agents targeting PI3K are under development in early-phase clinical trials and may demonstrate benefit in combination with chemotherapy or other targeted agents such as mitogen-activated protein kinase inhibitors for the treatment of triple-negative or basal-like breast cancer.
Department of Breast Medical Oncology and Phase I Program, The University of Texas, MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA. smoulder@mdanderson.org
Stacy L
SL
Moulder
D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000201:enzymology*; D005260:Female; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods; D009363:Neoplasm Proteins / Q000502:physiology*; D018295:Neoplasms, Basal Cell / Q000188:drug therapy / Q000201:enzymology*; D058539:Phosphatidylinositol 3-Kinase / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects
D000964:Antimetabolites, Antineoplastic; D009363:Neoplasm Proteins; D058539:Phosphatidylinositol 3-Kinase