title: Molecular mechanisms of tumor resistance to PI3K-mTOR-targeted therapy.
abstract: Deregulation of the phosphatidylinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) signaling pathway occurs frequently in a wide range of human cancers and is a major driving force in tumorigenesis. Thus, small molecules targeting this pathway are under active development as anticancer therapeutics. Although small-molecule inhibitors of the PI3K-mTOR pathway have shown promising clinical efficacy against human cancers, the emergence of drug resistance may limit their success in the clinic. To date, several resistance mechanisms, including both PI3K-dependent and -independent mechanisms, have been described. Here, we summarize the current understanding of resistance mechanisms to PI3K-mTOR inhibitors and discuss potential strategies for overcoming resistance for potential clinical application.
authors.affiliation: Genome Institute of Singapore, Agency for Science, Technology and Research, Biopolis, Singapore. tanj@gis.a-star.edu.sg
authors.forename: Jing
authors.initials: J
authors.lastname: Tan
authors.forename: Qiang
authors.initials: Q
authors.lastname: Yu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D016259:Genes, myc; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D015398:Signal Transduction; D020123:Sirolimus / Q000494:pharmacology / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D016271:Proto-Oncogene Proteins c-myc; D020123:Sirolimus; D058570:TOR Serine-Threonine Kinases; C546842:MTOR protein, human