Large-scale screening for somatic mutations in lung cancer

In squamous-cell carcinoma and small-cell lung carcinomas, several novel driver mutations are being investigated as potentially actionable targets: amplification of FGFR1, PIK3CA,9 and the sequence of the entire 3·2 kb coding region of DDR2.5,10DDR2 mutations can be detected at a frequency of 3% in both adenocarcinoma and squamous-cell carcinoma.11 On the basis of this knowledge, new initiatives for treatment of lung squamous-cell carcinoma are in progress, such as the Lung Cancer Master Protocol (Lung-MAP), a unique public-private partnership in the USA, including the US Food and Drug Administration.12 The Network Genomic Medicine (NGM) in Cologne, Germany, was the first group to describe distribution of genotypes and survival with targeted therapy compared with chemotherapy in distinct genotypes.10 Since then, the NGM has made great progress, implementing genotyping by next-generation sequencing as well as other initiatives in implementing genomic-driven treatment trials, such as for ROS1 (EUCROSS; NCT02183870).13 The Lung Cancer Mutation Consortium (LCMC) determined the frequency of oncogenic drivers, the proportion of patients treated with genotype-directed therapy, and survival in 1007 patients in the USA.