Dr. Saunthararajah on Mechanisms of Resistance to 5-Azacytidine /Decitabine in MDS-AML

Yogenthiran Saunthararajah, MD, Department of Hematologic Oncology and Blood Disorders at Cleveland Clinic, professor of Medicine, co-leader, Developmental Therapeutics Program of the Case Comprehensive Cancer Center, discusses mechanisms of resistance to 5-azacytidine and decitabine in patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML).

5-azacytadine and decitabine are the only two FDA approved agents to treat all subtypes of MDS, and are also used to treat AML, Saunthararajah explains. Both agents are engineered to deplete the DNMT1 protein from cancer cells. They are not curative regimens, however, as the majority of patients relapse.

In understanding the cause of relapse, researchers sought to determine if these agents effectively erase DNMT1 or if cancer cells continue growth regardless of protein status. Results of a recent study suggest that these agents are not depleting DNMT1, Saunthararajah says.