title: Mechanisms of targeted therapy resistance take a de-TOR.
abstract: The effectiveness of cancer therapeutics targeting signal transduction pathways is comprised of a diversity of mechanisms that drive de novo or acquired resistance. Two recent studies identify mTOR activation as a point of convergence of mechanisms that cause resistance to inhibitors of the Raf-MEK-ERK and PI3K signaling.
authors.affiliation: Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Leanna R
authors.initials: LR
authors.lastname: Gentry
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Martin
authors.forename: Channing J
authors.initials: CJ
authors.lastname: Der
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics*; D005260:Female; D006801:Humans; D008545:Melanoma / Q000201:enzymology* / Q000235:genetics*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors*; D046912:Multiprotein Complexes / Q000037:antagonists & inhibitors*; D009154:Mutation / Q000235:genetics*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*
chemical_list: D046912:Multiprotein Complexes; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D048493:Proto-Oncogene Proteins B-raf; D058570:TOR Serine-Threonine Kinases; D020929:Mitogen-Activated Protein Kinase Kinases
references.citation: N Engl J Med. 2012 Jul 12;367(2):107-14
references.pmid: 22663011
references.citation: Sci Transl Med. 2013 Jul 31;5(196):196ra98
references.pmid: 23903755
references.citation: Mol Cancer Ther. 2012 Feb;11(2):317-28
references.pmid: 22188813
references.citation: Clin Cancer Res. 2013 Aug 15;19(16):4326-34
references.pmid: 23770823
references.citation: N Engl J Med. 2011 Jun 30;364(26):2507-16
references.pmid: 21639808
references.citation: Nature. 2002 Jun 27;417(6892):949-54
references.pmid: 12068308
references.citation: J Clin Oncol. 2012 Jan 20;30(3):282-90
references.pmid: 22162589
references.citation: Sci Transl Med. 2013 Jul 31;5(196):196ra99
references.pmid: 23903756
references.citation: Lancet. 2012 Jul 28;380(9839):358-65
references.pmid: 22735384
references.citation: Eur J Cancer. 2013 Apr;49(6):1297-304
references.pmid: 23290787