glasdegib + decitabine

Glasdegib + decitabine is a combination therapy tested for the treatment of acute myeloid leukemia (AML). Glasdegib is a small molecule inhibitor of the Hedgehog signaling pathway, specifically targeting the transmembrane receptor smoothened (SMO). By inhibiting SMO, glasdegib disrupts aberrant Hedgehog pathway activity, which is implicated in the maintenance of leukemic stem cells and the proliferation of malignant cells. Decitabine is a hypomethylating agent that inhibits DNA methyltransferase, leading to decreased DNA methylation, impaired cancer cell replication, and promotion of cell death. The rationale for combining these therapies is based on preclinical evidence that hypomethylating agents (like decitabine) can sensitize AML cells to Hedgehog pathway inhibition, potentially enhancing efficacy. Clinical study of this specific combination (GLAD-AML trial) for AML was initiated but terminated early due to insufficient patient accrual, and has not reached widespread clinical use. Both drugs have different mechanisms: glasdegib targets leukemic stem cell persistence and decitabine inhibits tumor cell growth via epigenetic modulation[2][4].

Other names

glasdegib plus decitabineglasdegib and decitabine