2020 Volume 66 Issue 5 Pages 403-409
Driver oncogenes are defined as oncogenes showing mutations that are responsible for the development and proliferation of malignant neoplasms. Driver mutations represent the Achilles heel of tumors, because tumor proliferation is dramatically suppressed once these gene products are inhibited using specific molecular targeted therapy. Non-small-cell lung cancer (NSCLC) was initially sub-classified into adenocarcinoma, squamous cell carcinoma, and large cell carcinoma based on microscopic findings.
However, new information on a driver oncogene called epidermal growth factor receptor (EGFR) mutation and its specific inhibitor changed the sub-classification of NSCLC. After the discovery of EGFR mutation and its specific inhibitor, several other driver oncogenes and their specific inhibitors were also discovered, adding to the sub-classification of NSCLC. Consequently, testing for driver oncogenes became essential for selecting the optimal treatment for advanced NSCLC. Earlier, these driver oncogenes were tested for individually, but next-generation sequencing technology - which enables multiplex driver oncogene testing - has recently been introduced into daily clinical practice. However, sample quality and quantity are essential in order to obtain complete results of genetic alterations.
Treatment with inhibitors against driver oncogenes can shrink tumors dramatically, but tumors become resistant in 10-18 months. Mechanisms underlying resistance to specific inhibitors have been investigated, and novel drugs have been developed to overcome resistance. However, it remains challenging to cure advanced NSCLC with mutations in driver oncogenes. Therefore, immunotherapy should be introduced with the aim of inhibiting cancer progression long-term, and further investigation is warranted in this regard.