NAD+ metabolism restriction boosts high-dose melphalan efficacy in patients with multiple myeloma.

ABSTRACT:

Abstract

Elevated levels of the NAD+-generating enzyme nicotinamide phosphoribosyltransferase (NAMPT) are a common feature across numerous cancer types. Accordingly, we previously reported pervasive NAD+ dysregulation in multiple myeloma (MM) cells in association with upregulated NAMPT expression. Unfortunately, albeit being effective in preclinical models of cancer, NAMPT inhibition has proven ineffective in clinical trials because of the existence of alternative NAD+ production routes using NAD+ precursors other than nicotinamide. Here, by leveraging mathematical modeling approaches integrated with transcriptome data, we defined the specific NAD+ landscape of MM cells and established that the Preiss-Handler pathway for NAD+ biosynthesis, which uses nicotinic acid as a precursor,

SUBMITTER: Soncini D 

PROVIDER: S-EPMC11909440 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature