fulvestrant + selumetinib

Fulvestrant + selumetinib is a combination therapy investigated for the treatment of advanced hormone receptor-positive breast cancer. Fulvestrant is a selective estrogen receptor degrader (SERD) that binds to and accelerates degradation of the estrogen receptor alpha (ERα), thereby inhibiting estrogen signaling and tumor growth in ER-positive breast cancers. Selumetinib is a small molecule inhibitor targeting MEK1/2 within the mitogen-activated protein kinase (MAPK) pathway, which is implicated in resistance to endocrine therapies. The rationale for combining these agents was to overcome or delay resistance mechanisms by simultaneously blocking ER signaling and MAPK pathway activation. However, clinical trials have shown that this combination did not improve outcomes compared to fulvestrant alone and was associated with increased toxicity[1][6].