FCN-437c + fulvestrant

FCN-437c + fulvestrant is a combination therapy under investigation for the treatment of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer. FCN-437c is a novel, orally available, potent, and selective small molecule inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6). It acts by blocking the CDK4/6-mediated phosphorylation of retinoblastoma protein (Rb), thereby arresting cell cycle progression from G1 to S phase and inhibiting tumor cell proliferation. Fulvestrant is an established estrogen receptor antagonist that binds to and degrades the estrogen receptor, leading to inhibition of estrogen signaling in breast cancer cells. The combination aims to overcome resistance mechanisms associated with endocrine therapy alone by targeting both cell cycle regulation and hormone signaling pathways[1][5]. Preclinical studies have shown that FCN-437c has good blood-brain barrier penetration and improved potency compared to currently approved CDK4/6 inhibitors when used in combination with agents like fulvestrant[1]. Clinical trials are ongoing primarily in China for advanced/metastatic HR+/HER2− breast cancer.