A mutation in the DDR2 gene may make some patients with squamous cell cancer (SCC) of the lung more responsive to the drug dasatinib, an existing therapy for chronic myelogenous leukemia.
These findings—reported at the American Association for Cancer Research (AACR) annual meeting held April 2-6, 2011, in Orlando, Florida, and in the new AACR journal Cancer Discovery (http://cancerdiscovery.aacrjournals.org/content/early/2011/03/17/2159-8274.CD-11-0005.full.pdf)—“clearly encourage a clinical trial to test dasatinib in the setting of squamous cell lung cancer,” according to lead researcher Matthew Meyerson, MD, PhD, a professor of pathology at the Dana-Farber Cancer Institute in Boston.
Gene sequencing performed by Meyerson’s group identified mutations in the DDR2 kinase gene in 3.8% of lung SCCs and cell lines. The kinase inhibitor dasatinib selectively killed the mutant cell lines, and tumors established from the mutant cell lines demonstrated sensitivity to the agent in xenograft models. Furthermore, a patient with lung SCC that responded to dasatinib and erlotinib treatment had a DDR2 kinase domain mutation.
“These data suggest that gain-of-function mutations in DDR2 are important oncogenic events and are amenable to therapy with dasatinib,” wrote the researchers. “Because dasatinib is already approved for use, these findings could be used to rapidly generate clinical trials.”