Targeted Therapy on the Horizon for Squamous Cell Lung Cancer?

The march toward personalized cancer care may have taken a step forward with the discovery of a potential biomarker for the treatment of squamous cell cancer (SCC) of the lung. Researchers at the American Association for Cancer Research (AACR) 102nd Annual Meeting described how a mutation in the discoidin domain receptor 2 (DDR2) gene might identify which patients with SCC will respond to dasatinib. The research appears in the April issue of the new AACR journal Cancer Discovery.

In the study, scientists at the Dana-Farber Cancer Institute examined 290 SCC samples and identified DDR2 mutations in nearly 4% (n = 11) of them. The investigators subsequently discovered that patients with DDR2 mutations had a clinical response to dasatinib, which appeared to block the oncogenic effects of the mutations. Dasatinib, an orally administered tyrosine kinase inhibitor, is currently FDA-approved for the treatment of newly-diagnosed adult patients with Philadelphia chromosome-positive chronic myelogenous leukemia in chronic phase (CP-CML).

The researchers are eager for new studies to build on their findings. “We hope our data may stimulate the initiation of larger clinical trials of dasatinib or other tyrosine kinase inhibitors in patients with lung SCC and testing of these patients for DDR2 mutations, potentially leading to a less toxic and more effective treatment for this deadly disease.”

Eric B. Haura, MD

DDR2

According to the AACR, SCC affects approximately 50,000 people annually in the United States. It is the second-largest subtype of non—small cell lung cancer (NSCLC), which accounts for approximately 85% of all incidences of lung cancer. Although there are targeted treatments for NSCLC’s primary subtype, adenocarcinoma, no personalized therapies currently exist for SCC. "Adenocarcinoma is more frequent so most of the research to date has focused on adenocarcinoma instead of other histology; but, obviously, things are moving now in squamous cell," said one of the study's authors, Eric B. Haura, MD, program leader, Experimental Therapeutics, and director, Lung Comprehensive Research Center, at the H. Lee Moffitt Cancer Center, Tampa, Florida.

Source: Hammerman P, Sos M, Ramos A, et al. Mutations in the DDR2 kinase gene identify a novel therapeutic target in squamous cell lung cancer [published online ahead of print April 3, 2011]. Cancer Discovery. doi:10.1158/2159-8290.CD-ITI11-01.