mTOR: Role in cancer, metastasis and drug resistance

• Published in: Seminars in cancer biology Vol. 59; pp. 92 - 111
• Main Author: Murugan, Avaniyapuram Kannan
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-12-2019
• Subjects: Animals; Biomarkers, Tumor; Cancer; Disease Susceptibility; Drug Resistance, Neoplasm - genetics; Enzyme Activation; Humans; Inhibitors; Mechanistic Target of Rapamycin Complex 1 - metabolism; Mechanistic Target of Rapamycin Complex 2 - metabolism; Metastasis; Molecular target; Molecular Targeted Therapy; mTOR; Mutation; Mutation Rate; Neoplasm Metastasis; Neoplasm Staging; Neoplasms - drug therapy; Neoplasms - etiology; Neoplasms - metabolism; Neoplasms - pathology; Oncogene; Precision medicine; Protein Kinase Inhibitors - pharmacology; Protein Kinase Inhibitors - therapeutic use; Resistance; Signal Transduction; TOR Serine-Threonine Kinases - genetics; TOR Serine-Threonine Kinases - metabolism; Resistance; Molecular target; Inhibitors; Precision medicine; Oncogene; mTOR; Mutation; Metastasis; Cancer
• ISSN: 1044-579X; 1096-3650
• DOI: 10.1016/j.semcancer.2019.07.003

Mammalian target of rapamycin (mTOR) is a serine/threonine kinase that gets inputs from the amino acids, nutrients, growth factor, and environmental cues to regulate varieties of fundamental cellular processes which include protein synthesis, growth, metabolism, aging, regeneration, autophagy, etc. The mTOR is frequently deregulated in human cancer and activating somatic mutations of mTOR were recently identified in several types of human cancer and hence mTOR is therapeutically targeted. mTOR inhibitors were commonly used as immunosuppressors and currently, it is approved for the treatment of human malignancies. This review briefly focuses on the structure and biological functions of mTOR. It extensively discusses the genetic deregulation of mTOR including amplifications and somatic mutations, mTOR-mediated cell growth promoting signaling, therapeutic targeting of mTOR and the mechanisms of resistance, the role of mTOR in precision medicine and other recent advances in further understanding the role of mTOR in cancer.