decitabine + rapamycin

Decitabine + rapamycin is a combination therapy being investigated for the treatment of relapsed or refractory acute myeloid leukemia (AML). Decitabine is a cytidine antimetabolite that, upon incorporation into DNA, covalently binds and inhibits DNA methyltransferases (DNMTs), leading to DNA hypomethylation and the potential reactivation of silenced tumor suppressor genes. Rapamycin (sirolimus) is a macrocyclic lactone that inhibits the mechanistic target of rapamycin (mTOR), specifically the mTORC1 complex, by binding to the immunophilin FK506-binding protein 12 (FKBP12). The mTOR pathway is frequently overactive in AML, contributing to cell proliferation and resistance to apoptosis. By combining these two agents, the regimen seeks to exploit synergistic effects between epigenetic modulation and the inhibition of key survival pathways to improve outcomes in patients with advanced myeloid malignancies. This specific combination is being developed in clinical trials led by the University of Rochester.

Other names

decitabine and rapamycindecitabine and sirolimus