Dr. Swords on Anti-Tumor Effects of IMG-98 in AML

Ronan T. Swords, MD, PhD, FRCPI, FRCPath, co-leader of the Leukemia/Lymphoma/Myeloma Site Disease Group at Sylvester Comprehensive Cancer at the University of Miami Miller School of Medicine, discusses preclinical findings demonstrating that the small-molecule inhibitor IMG-98 effectively augments pro-differentiation effects of all-trans-retinoic acid (ATRA)—based therapies in acute myeloid leukemia (AML).

Previous studies have shown the efficacy of tranylcypromine (TCP) combined with ATRA in patients with AML, Swords explains. However, the conflict with using TCP as an LSD-1 inhibitor is that it is neither potent nor selective.

In this preclinical study, IMG-98, another LSD-1 inhibitor, was found to augment ATRA pro-differentiation effects. IMG-98 binds with FAD, and when combined with ATRA, it activates the retinoic-acid signaling pathway. In conclusion, this regimen was found to potently induce more differentiation versus ATRA alone, Swords says.