Selective Hdac Inhibitors For Hematological Malignancies

HDAC inhibitors that could reduce pan-HDAC treatment side effects.

Pan-HDAC inhibitors are an FDA-approved treatment for cancers such as multiple myeloma and cutaneous T-cell lymphoma. However, pan-HDAC inhibitors block HDACs involved in important cellular functions and can cause serious adverse side effects such as cardiac toxicity.

University of Utah researchers have developed selective HDAC inhibitors for hematological malignancies that could reduce the side effects of pan-HDAC inhibitors. The selective HDAC inhibitors, when used with doxorubicin or alone, have decreased leukemia burden in patient-derived xenograft mouse models.

Pre-Clinical Validation

• Selective inhibition of HDAC1 and HDAC2 has decreased side effects compared to non-selective pan-Hdac inhibitors.
• Patient-derived xenograft mouse models show benefit with these inhibitors when they are either alone or combined with other chemotherapeutics.

Tharkar-Promod S, et al (2018). HDAC1,2 inhibition and doxorubicin impair Mre11-dependent DNA repair and DISC to override BCR-ABL1-driven DSB repair in Philadelphia chromosome-positive B-cell precursor acute lymphoblastic leukemia. Leukemia. 32: 49–60.

Jason Young
(801) 587-0519
jason.r.young@utah.edu