Next-generation sequencing–based clinical testing for lung cancer in Japan

Recent insight into the molecular basis of lung cancer has led to changes in the treatment of this disease. The identification of driver genetic changes, such as those affecting the epidermal growth factor receptor (EGFR) (1-3) and anaplastic lymphoma kinase (ALK) genes (4,5), has already been successfully translated into clinical practice with the implementation of treatment with approved targeted agents (erlotinib, gefitinib, and afatinib for activating mutations of EGFR, and crizotinib and alectinib for rearrangements of ALK). The subsequent discovery of ROS1 and RET rearrangements as oncogenic drivers and potential therapeutic targets has shown that several chromosomal translocations and corresponding gene fusions can give rise to non–small cell lung cancer (NSCLC) (6-9). Given that mutations of EGFR, or KRAS and rearrangements involving ALK appear to be mutually exclusive, the need to test for many genetic alterations with a limited amount of collected tissue poses a problem for the “one companion diagnostic–one drug” paradigm of targeted therapy as applied to lung cancer and current clinical practice. The clinical implementation of genomic profiling for NSCLC with high-throughput and multiplex genotyping tests is thus urgently required in order to allow prioritization of appropriate therapies for individual patients