Can phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibition ERase them all?
Seventy percent of breast tumors are estrogen receptor (ER) positive. Although endocrine therapy is successful for the majority of patients with ER-positive tumors, approximately 30% show de novo or acquired resistance and the underlying molecular mechanisms and biomarkers that predict such resistance remain elusive. Two recent papers report that hyperactivation of the phosphatidylinositol 3-kinase (PI3K) pathway produces resistance to tamoxifen. This raises the possibility that combining endocrine therapy and PI3K inhibition may be more effective than monotherapy for treating ER-positive breast tumors, either as first-line therapy for tumors with high PI3K activity or after the development of resistance to endocrine therapy.
Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
Dominique S
DS
Meyer
Mohamed
M
Bentires-Alj
D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000517:prevention & control; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011960:Receptors, Estrogen / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D013629:Tamoxifen / Q000627:therapeutic use*
D018931:Antineoplastic Agents, Hormonal; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011960:Receptors, Estrogen; D013629:Tamoxifen; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases