RET and other genes: therapeutic targets in lung adenocarcinoma

Abstract

SUMMARY:  The RET fusion gene was recently identified as a new druggable driver gene present in 1–2% of lung adenocarcinomas (LADCs). Vandetanib (ZD6474) and cabozantininb (XL184), two RET tyrosine kinase inhibitors approved by US FDA for the therapy of medullary thyroid cancer, have demonstrated therapeutic effectiveness in a few RET fusion-positive LADC patients. Several clinical trials are under way to address the therapeutic effects of RET tyrosine kinase inhibitors, including these two drugs. Multiplex diagnosis of aberrations in druggable driver oncogenes, such as EGFR, ALK, RET, ROS1, HER2/ERBB2, BRAF and others, in clinical samples will facilitate the design of personalized therapies for LADC based on protein kinase inhibitors. The development of therapeutic methods targeting aberrations of other genes, such as chromatin remodeling genes, is necessary to further improve the treatment of LADC.