MK-2206 + fulvestrant

MK-2206 + fulvestrant is a combination therapy consisting of an allosteric pan-AKT inhibitor (MK-2206) and an estrogen receptor down-regulator (fulvestrant). This combination targets both the PI3K/AKT pathway and estrogen receptor signaling in estrogen receptor-positive (ER+) breast cancer. MK-2206 works by blocking AKT activation, which is involved in endocrine resistance mechanisms, while fulvestrant degrades the estrogen receptor, preventing estrogen-stimulated tumor growth. The combination has shown synergistic effects in preclinical models, particularly in long-term estrogen-deprived cell lines where either agent alone was ineffective.