Therapeutics: Estrogen receptor; LYN kinase (LYN); phosphoinisitide 3-kinase (PI3K)
INDICATION: Breast cancerStudies in mice and human samples suggest inhibiting LYN could help treat estrogen receptor-positive breast cancers resistant to anti-estrogen therapy. In biopsies from breast cancer patients treated with estrogen deprivation therapy and breast cancer data sets, genome analysis identified five recurrent activating mutations in LYN. In a mouse xenograft model of estrogen receptor-positive breast cancer, the estrogen receptor antagonist Faslodex fulvestrant plus inhibition of LYN with the kinase inhibitors Sprycel dasatinib and buparlisib (BKM120) induced near-complete tumor regression and was more potent than individual agents. Next steps could include testing the triple inhibitor combination across genetically distinct estrogen receptor-positive breast cancers.AstraZeneca plc markets the selective estrogen receptor downregulator Faslodex to treat breast cancer.Bristol-Myers Squibb Co. markets Sprycel to treat acute lymphoblastic leukemia and chronic myelogenous leukemia.Novartis AG has buparlisib in Phase III testing to treat breast cancer.
TARGET/MARKER/PATHWAY: Estrogen receptor; LYN kinase (LYN); phosphoinisitide 3-kinase (PI3K)...