RET fusion gene: translation to personalized lung cancer therapy

Cancer Sci. 2013 Nov;104(11):1396-400. doi: 10.1111/cas.12275. Epub 2013 Oct 1.


Development of lung adenocarcinoma (LADC), the most frequent histological type of lung cancer, depends in many cases on the activation of "driver" oncogenes such as KRAS, epidermal growth factor receptor (EGFR), and anaplastic lymphoma kinase (ALK). Inhibitors that target the EGFR and ALK tyrosine kinases show therapeutic effects against LADCs containing EGFR gene mutations and ALK gene fusions, respectively. Recently, we and others identified the RET fusion gene as a new targetable driver gene in LADC. The RET fusions occur in 1-2% of LADCs. Existing US Food and Drug Administration-approved inhibitors of RET tyrosine kinase show promising therapeutic effects both in vitro and in vivo, as well as in a few patients. Clinical trials are underway to investigate the therapeutic effects of RET tyrosine kinase inhibitors, such as vandetanib (ZD6474) and cabozantinib (XL184), in patients with RET fusion-positive non-small-cell lung cancer.

Publication types

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

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / epidemiology
  • Adenocarcinoma / genetics*
  • Adenocarcinoma of Lung
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Clinical Trials, Phase II as Topic
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / epidemiology
  • Lung Neoplasms / genetics*
  • Molecular Targeted Therapy*
  • Oncogene Proteins, Fusion / antagonists & inhibitors
  • Oncogene Proteins, Fusion / genetics*
  • Precision Medicine
  • Prevalence
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • Proto-Oncogene Proteins c-ret / antagonists & inhibitors
  • Proto-Oncogene Proteins c-ret / genetics*


  • Antineoplastic Agents
  • Oncogene Proteins, Fusion
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins c-ret
  • RET protein, human