Suppression of insulin feedback enhances the efficacy of PI3K inhibitors

• Published in: Nature (London) Vol. 560; no. 7719; pp. 499 - 503
• Main Authors: Hopkins, Benjamin D., Pauli, Chantal, Du, Xing, Wang, Diana G., Li, Xiang, Wu, David, Amadiume, Solomon C., Goncalves, Marcus D., Hodakoski, Cindy, Lundquist, Mark R., Bareja, Rohan, Ma, Yan, Harris, Emily M., Sboner, Andrea, Beltran, Himisha, Rubin, Mark A., Mukherjee, Siddhartha, Cantley, Lewis C.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.08.2018; Nature Publishing Group
• Subjects: 1-Phosphatidylinositol 3-kinase; 13; 13/89; 59; 59/5; 59/78; 631/67/1059/2326; 631/67/1059/602; 64; 64/60; 82/29; 82/51; 96; 96/1; 96/106; 96/31; 96/95; Adipose tissue; Animals; Blood glucose; Blood Glucose - metabolism; Breast cancer; Cancer; Cancer therapies; Cell Proliferation - drug effects; Cell Survival - drug effects; Clinical trials; Colorectal cancer; Diabetes; Diabetes therapy; Diet; Disease Models, Animal; Dosage and administration; Drug therapy; Effectiveness; Enzymes; Feedback; Feedback, Physiological - drug effects; Glucose; Glucose metabolism; Glycogen; Humanities and Social Sciences; Hyperglycemia; Hypoglycemic agents; Inhibitors; Insulin; Insulin - metabolism; Insulin resistance; Kinase inhibitors; Kinases; Letter; Lipids; Liver; Male; Medical research; Metabolism; Mice; Mice, Inbred C57BL; Mice, Nude; multidisciplinary; Muscles; Mutation; Neoplasms - drug therapy; Neoplasms - enzymology; Neoplasms - metabolism; Neoplasms - pathology; Oncology; Pancreas; Patient outcomes; Patients; Peptides; Pharmacology; Phosphatases; Phosphoinositide-3 Kinase Inhibitors; Phospholipids; Physiological aspects; Polysaccharides; Prostate cancer; Protein Kinase Inhibitors - pharmacology; PTEN protein; Science; Science (multidisciplinary); Signal transduction; Signal Transduction - drug effects; Signaling; Skeletal muscle; Survival analysis; TOR protein; TOR Serine-Threonine Kinases - metabolism; Toxicity; Tumors
• ISSN: 0028-0836; 1476-4687; 1476-4687
• DOI: 10.1038/s41586-018-0343-4

Mutations in PIK3CA , which encodes the p110α subunit of the insulin-activated phosphatidylinositol-3 kinase (PI3K), and loss of function mutations in PTEN , which encodes a phosphatase that degrades the phosphoinositide lipids generated by PI3K, are among the most frequent events in human cancers 1...