Novel BRD4-Degrading Proteolysis Targeting Chimera (PROTACs) Exert Potent Single Agent and Synergistic Activity with Ibrutinib and Venetoclax Against Human Mantle Cell Lymphoma (MCL) Cells

MCL cells exhibit chronic-active BCR signaling and downstream pro-growth and pro-survival NFkB activity. Ibrutinib, a covalent inhibitor of Bruton's tyrosine kinase (BTK) yields high overall response rate in relapsed/refractory MCL, but approximately 40% of patients demonstrate primary refractory/resistant disease. Mutations in CARD11/IKBKB/TRAF2/BIRC3/NIK or in B-cell receptor (BCR) signaling induce activity of the classical or alternative NFkB pathway, conferring resistance to ibrutinib in MCL.
Source: Clinical Lymphoma, Myeloma and Leukemia - Category: Hematology Authors: Source Type: research