Characterization of the Discoidin Domain Receptor 2 Kinase as a Novel Therapeutic Target for Squamous Cell Lung Cancer.

摘要

This program has undertaken the study of the discoidin domain 2 (DDR2) tyrosine kinase as a potential therapeutic target in squamous cell lung cancer. We identified mutations in the DDR2 gene in a cohort of 290 individuals with this type of lung cancer and showed that these mutations are oncogenic when expressed in cell lines. Importantly, we showed that DDR2- driven cellular transformation sensitizes cancer cells to treatment with tyrosine kinase inhibitors which target DDR2, namely dasatinib. We have generated cellular and animals models to study DDR2, have studied the mechanisms by which DDR2 transforms cells and have worked to develop more selective inhibitors of DDR2 as well as identify mechanisms of cellular resistance to dasatinib therapy. This work has led to a publication in Cancer Discovery and has been presented at several scientific meetings including AACR and IASLC. Dasatinib is now being studied in the clinic as a DDR2 inhibitor in a national phase II trial for patients with squamous cell lung cancer, a disease for which no targeted agents are approved at this time.