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

• Published in: Nature (London) Vol. 569; no. 7757; pp. 570 - 575
• Main Authors: Chowdhry, Sudhir, Zanca, Ciro, Rajkumar, Utkrisht, Koga, Tomoyuki, Diao, Yarui, Raviram, Ramya, Liu, Feng, Turner, Kristen, Yang, Huijun, Brunk, Elizabeth, Bi, Junfeng, Furnari, Frank, Bafna, Vineet, Ren, Bing, Mischel, Paul S.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.05.2019; Nature Publishing Group
• Subjects: 13; 13/1; 13/106; 13/109; 13/2; 13/31; 13/44; 13/51; 13/89; 14; 38; 38/32; 45; 45/15; 45/22; 45/29; 45/77; 45/90; 59; 631/67/2327; 631/67/69; 64/60; 82; 96; Adenine; Amplification; Animals; Cancer; Cancer genetics; Carbon-Nitrogen Ligases with Glutamine as Amide-N-Donor - metabolism; Cell Death; Cell Line, Tumor; Cell survival; Constraining; CRISPR; Cytokines - antagonists & inhibitors; Cytokines - genetics; Cytokines - metabolism; Deoxyribonucleic acid; Dependence; DNA; Drug delivery; Enhancer Elements, Genetic - genetics; Enzymes; Epigenesis, Genetic; Epigenetics; Female; Gene Amplification; Gene expression; Gene Expression Regulation, Neoplastic; Genetic aspects; Genomics; Genotypes; Health aspects; Humanities and Social Sciences; Humans; Letter; Mathematical models; Metabolic pathways; Metabolism; Mice; multidisciplinary; NAD; NAD - metabolism; Neoplasms - enzymology; Neoplasms - genetics; Neoplasms - metabolism; Niacinamide; Nicotinamide; Nicotinamide adenine dinucleotide; Nicotinamide Phosphoribosyltransferase - antagonists & inhibitors; Nicotinamide Phosphoribosyltransferase - genetics; Nicotinamide Phosphoribosyltransferase - metabolism; Oncology; Pentosyltransferases - genetics; Pentosyltransferases - metabolism; Pharmacology; Phosphotransferases (Alcohol Group Acceptor) - metabolism; Precision medicine; Purines; Salvage; Science; Science (multidisciplinary); Survival; Synthesis; Tissues; Tumors

Precision oncology hinges on linking tumour genotype with molecularly targeted drugs 1 ; however, targeting the frequently dysregulated metabolic landscape of cancer has proven to be a major challenge 2 . Here we show that tissue context is the major determinant of dependence on the nicotinamide ade...