everolimus + giredestrant

everolimus + giredestrant is an investigational oral combination therapy being evaluated for the treatment of estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2–), locally advanced or metastatic breast cancer, particularly in patients who have progressed after prior endocrine therapy and cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) treatment. Everolimus is an approved small molecule inhibitor of the mammalian target of rapamycin (mTOR), which disrupts cell growth and proliferation pathways. Giredestrant is a next-generation, highly potent, non-steroidal, oral selective estrogen receptor degrader (SERD) that antagonizes and degrades the estrogen receptor, leading to inhibition of ER signaling regardless of ESR1 mutation status. The combination aims to overcome resistance mechanisms following CDK4/6i therapy by targeting both ER signaling and mTOR pathways. This regimen is currently under investigation in phase III clinical trials for its efficacy and safety compared to standard endocrine therapies plus everolimus[1][2][3][4][5].