EGFR T790M ctDNA testing platforms and their role as companion diagnostics: Correlation with clinical outcomes to EGFR-TKIs

Cancer Lett. 2017 Sep 10:403:186-194. doi: 10.1016/j.canlet.2017.06.008. Epub 2017 Jun 19.

Abstract

Somatic mutation in the epidermal growth factor receptor (EGFR) predict clinical response to EGFR tyrosine kinase inhibitors in non-small cell lung cancer (NSCLC) and is a promising target for personalised medicine. EGFR mutations have prognostic value. Initially patients respond well to tyrosine kinase inhibitors but finally they would develop resistance and about 50% of this resistance can be attributed to the emergence of EGFR resistant mutation, T790M. This necessitates the need for genetic testing for clinical management of patients. Molecular testing has become the standard of care in patients with NSCLCs based on the recommendations of standard guidelines. Though there are several platforms for EGFR mutation detection, highly sensitive platforms for clinical applicability as companion diagnostics for ctDNA based testing are emerging. Due to the dynamic changes in the T790M mutation during tyrosine kinase inhibitor (TKI) treatment, real-time monitoring of these genetic alterations is mandate for planning treatment strategies. With the advent of third generation TKIs that potentially target T790M, improvement in clinical outcome is documented in patients with NSCLCs. Managing these outcomes with appropriate companion diagnostics using ctDNA in early detection of these genetic alterations will improve patient care.

Keywords: Drug resistance; EGFR T790M mutation; NSCLC; Tyrosine kinase inhibitors.

Publication types

  • Review

MeSH terms

  • Animals
  • Biomarkers, Tumor / antagonists & inhibitors
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / genetics*
  • Carcinoma, Non-Small-Cell Lung / blood
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / enzymology
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • DNA Mutational Analysis / methods*
  • Drug Resistance, Neoplasm / genetics
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / blood
  • ErbB Receptors / genetics*
  • Genetic Predisposition to Disease
  • Humans
  • Lung Neoplasms / blood
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / enzymology
  • Lung Neoplasms / genetics*
  • Molecular Targeted Therapy
  • Mutation*
  • Neoplastic Cells, Circulating / metabolism*
  • Neoplastic Cells, Circulating / pathology
  • Patient Selection
  • Phenotype
  • Precision Medicine
  • Predictive Value of Tests
  • Protein Kinase Inhibitors / therapeutic use
  • Treatment Outcome

Substances

  • Biomarkers, Tumor
  • Protein Kinase Inhibitors
  • EGFR protein, human
  • ErbB Receptors