MK-2206 + anastrozole + fulvestrant

MK-2206 + anastrozole + fulvestrant is a combination therapy investigated primarily for the treatment of estrogen receptor-positive (ER+), HER2-negative metastatic breast cancer. The regimen combines three agents with distinct mechanisms: - **MK-2206** is an allosteric pan-AKT inhibitor that targets the PI3K/AKT signaling pathway, which is implicated in endocrine resistance in ER+ breast cancer. - **Anastrozole** is a non-steroidal aromatase inhibitor that reduces estrogen production, thereby limiting growth stimulation of hormone-sensitive tumors. - **Fulvestrant** is a selective estrogen receptor degrader (SERD) that binds to and accelerates degradation of the estrogen receptor, blocking its activity. Preclinical studies showed synergistic induction of apoptosis when combining MK-2206 with either estrogen deprivation or fulvestrant. Clinical phase I trials established recommended dosing and demonstrated tolerability for this triple combination in postmenopausal women with advanced ER+ breast cancer[1][2][9]. The primary developer and sponsor for clinical studies involving MK-2206 has been Merck.