Shades of T790M: Intratumor Heterogeneity in EGFR-Mutant Lung Cancer

Cancer Discov. 2015 Jul;5(7):694-6. doi: 10.1158/2159-8290.CD-15-0616.


In the setting of recent exciting clinical results and numerous ongoing trials, Piotrowska and colleagues explore mechanisms of acquired resistance to the mutant-specific EGFR inhibitor rociletinib, and demonstrate that loss of T790M, EGFR amplification, and small-cell transformation are all clinically relevant mechanisms of drug resistance. The authors provide a new paradigm for using quantitative assessment of the EGFR T790M:activation mutation allele frequency ratio to prognosticate responses to rociletinib and also demonstrate that plasma-based assessments of circulating tumor DNA can be used to monitor drug response and the emergence of drug resistance.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Comment

MeSH terms

  • Acrylamides / administration & dosage*
  • Drug Resistance, Neoplasm*
  • ErbB Receptors / genetics*
  • Humans
  • Lung Neoplasms / drug therapy*
  • Protein Kinase Inhibitors / administration & dosage*
  • Pyrimidines / administration & dosage*
  • Small Cell Lung Carcinoma / drug therapy*


  • Acrylamides
  • Protein Kinase Inhibitors
  • Pyrimidines
  • ErbB Receptors