SY-1365 + fulvestrant

SY-1365 + fulvestrant is an investigational combination therapy for advanced solid tumors, particularly focusing on hormone receptor-positive (HR+) breast cancer that is resistant to endocrine therapy and CDK4/6 inhibitors. SY-1365 is a selective and potent covalent cyclin-dependent kinase 7 (CDK7) inhibitor that disrupts cell cycle progression and transcriptional control, leading to decreased expression of oncogenic transcription factors and apoptosis in cancer cells. Fulvestrant is a selective estrogen receptor degrader (SERD) that antagonizes and degrades the estrogen receptor, reducing estrogen-driven transcription in breast cancer. Preclinical and early clinical studies reported synergistic antitumor activity when combining SY-1365 with fulvestrant in HR-positive breast cancer models resistant to prior CDK4/6 inhibitor therapy. The combination specifically potentiates inhibition of cell cycle regulators such as CDK1/CDK2 and the oncogene c-Myc. Development was led by Syros, with exploration also in solid tumors including ovarian cancer[1][2][3][4][6][7][9].