Posted November 25, 2013
Matthew Meyerson, M.D., Ph.D., Dana-Farber Cancer Institute, Boston, Massachusetts
The recent advancements in sequencing technologies have led to the discovery of oncogenic drivers associated with lung carcinogenesis and to the design of rationally targeted therapies against specific somatic mutations. Despite these technological advancements and the enormous bioinformatic data generated in recent years, targeted therapies against the currently known somatic mutations in lung cancer (mainly mutations in EGFR and ALK) vary in their effectiveness. All patients who initially respond to these therapies eventually develop resistance to them. Moreover, many patients do not harbor mutations in these two genes, indicating the heterogeneity of lung tumors and underscoring the need for novel therapeutic targets as well as multi-pronged therapeutic strategies that target several molecular pathways simultaneously.
Dr. Meyerson, recipient of a Fiscal Year 2011 Lung Cancer Research Program Investigator-Initiated Translational Research Award, aims to identify new therapeutic targets in lung cancer through a systemic approach for functional analysis of large numbers of somatic mutations. Leveraging the whole-exome non-small cell lung cancer somatic mutation data generated by The Cancer Genome Atlas project, the investigator is evaluating which of the newly discovered somatic mutations contribute to lung carcinogenesis and may serve as targets for therapeutic intervention. Although the study is in its initial stages, Dr. Meyerson has already uncovered several novel potential therapeutic targets for lung cancer for which drugs are already available or in development. For example, he validated somatic mutations in FGFR2 and FGFR3 as potential therapeutic targets in lung squamous cell carcinoma using existing inhibitors in clinical development. Novel somatic mutations in Ras pathway genes were observed to be oncogenic in lung adenocarcinoma and may be targeted by PI3K, MEK, or Raf inhibitors. Since relevant drugs for many of these mutations are already in clinical development, results of this study may allow lung cancer patients harboring these mutations to quickly be directed to the appropriate clinical trial.