CD38-Induced Metabolic Dysfunction Primes Multiple Myeloma Cells for NAD⁺-Lowering Agents.

ABSTRACT: Cancer cells fuel growth and energy demands by increasing their NAD⁺ biosynthesis dependency, which therefore represents an exploitable vulnerability for anti-cancer strategies. CD38 is a NAD⁺-degrading enzyme that has become crucial for anti-MM therapies since anti-CD38 monoclonal antibodies represent the backbone for treatment of newly diagnosed and relapsed multiple myeloma patients. Nevertheless, further steps are needed to enable a full exploitation of these strategies, including deeper insights of the mechanisms by which CD38 promotes tumorigenesis and its metabolic additions that could be selectively targeted by therapeutic strategies. Here, we present evidence that CD38 upregulation produces a pervasive intracellular-NAD⁺ depletion, which impairs mi

SUBMITTER: Becherini P 

PROVIDER: S-EPMC9952390 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature