NAD metabolic dependency in cancer is shaped by gene amplification and enhancer remodelling.

ABSTRACT: Precision oncology hinges on linking tumour genotype with molecularly targeted drugs¹; however, targeting the frequently dysregulated metabolic landscape of cancer has proven to be a major challenge². Here we show that tissue context is the major determinant of dependence on the nicotinamide adenine dinucleotide (NAD) metabolic pathway in cancer. By analysing more than 7,000 tumours and 2,600 matched normal samples of 19 tissue types, coupled with mathematical modelling and extensive in vitro and in vivo analyses, we identify a simple and actionable set of 'rules'. If the rate-limiting enzyme of de novo NAD synthesis, NAPRT, is highly expressed in a normal tissue type, cancers that arise from that tissue will have a high frequency of NAPRT amplification and be complet

SUBMITTER: Chowdhry S 

PROVIDER: S-EPMC7138021 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature