Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors (palbociclib and abemaciclib) and mammalian target of rapamycin (mTOR) inhibitors (everolimus) are effective agents for restoring endocrine sensitivity in patients with advanced breast cancer progression on prior aromatase inhibitors.
Everolimus is a mammalian target of rapamycin (m-TOR) inhibitor that has been approved for the treatment of hormone receptor-positive advanced breast cancer, metastatic renal cancer, and neuroendocrine tumors.
The impact of mammalian target of rapamycin inhibition on bone health in postmenopausal women with hormone receptor-positive advanced breast cancer receiving everolimus plus exemestane in the phase IIIb 4EVER trial.
Cellular changes in amino acids such as glutamine are sensed by the mammalian target of rapamycin (mTOR) complex, mTORC1, which is often deregulated in ER+ advanced breast cancer.
Cotargeting the mammalian target of rapamycin pathway and estrogen receptor may prevent or delay endocrine resistance in patients receiving first-line treatment for advanced breast cancer.
Everolimus (RAD001) is an inhibitor of mammalian target of rapamycin used in combination with exemestane to treat hormone receptor-positive advanced breast cancer.
Advances in drug development during the past two decades have provided numerous options for treatment of advanced breast cancer that include monotherapy with endocrine modulating agents and dual therapy that combines endocrine therapy with an inhibitor targeting the mammalian target of rapamycin serine-threonine kinase or cyclin-dependent kinase pathways known to be involved with resistance.
In the BOLERO-2 trial, everolimus (EVE), an inhibitor of mammalian target of rapamycin, demonstrated significant clinical benefit with an acceptable safety profile when administered with exemestane (EXE) in postmenopausal women with hormone receptor-positive (HR(+)) advanced breast cancer.