Working with an international team of scientists, researchers at Moffitt Cancer Center have started a first-of-its-kind clinical trial for patients with squamous cell lung cancer to test a unique inhibitor drug dasatinib. The drug is aimed at DDR2, a genetic mutation found in approximately 4 percent of squamous cell carcinomas of the lung.
Participating thoracic oncology clinics will screen tumor tissues for the DDR2 genetic mutations. In addition, genetic mutations will be screened from a bank of patient-donated tissue samples housed in Moffitt’s M2Gen® biorepository. The tissue data bank is made possible through Total Cancer Care®, a program that allows cancer patients to donate samples of their tumor tissues to advance research in personalized medicine. The protocol also allows consented patients to be contacted if a clinical trial becomes available based on their genetic profile.
According to Eric B. Haura, M.D., director of Moffitt’s Lung Cancer Center of Excellence, the most common type of lung cancer is non-small cell lung cancer. It accounts for about 85 percent of all lung cancers. Approximately 25 percent of those diagnosed with non-small cell lung cancer are of the squamous cell variety. However, few patients with squamous cell lung cancer respond to therapies used for other non-small cell lung cancers. Targeted therapy for squamous cell lung cancer has lagged behind adenocarcinoma, the most common type of lung cancer.
“Molecularly targeted therapy is highly effective for well-defined varieties of lung cancer,” Haura said. “With the introduction of molecular profiling that can quickly identify molecular ‘driver’ mutations, efforts at targeted drug therapy are rapidly improving.”
The U.S. Food and Drug Administration has approved dasatinib for the treatment of leukemia. Haura’s research studies the effect of this drug on lung cancer. Supported by Moffitt’s Specialized Programs of Research Excellence (SPORE) grant in lung cancer, the researchers used mass spectrometry-based proteomics to map all dasatinib targets in lung cancer and identify the activity. This information revealed insight into signaling pathways that are active in lung cancer cells involving several kinases, which act on and modify the activity of specific proteins. The researchers found that a number of kinases, especially tyrosine kinases, could be targeted by dasatinib. One of the proteins identified was DDR2, a receptor tyrosine kinase. This was supported by the results of a dasatinib clinical trial at Moffitt where one patient who has a DDR2 gene mutation showed a dramatic response. These studies clarified where in the molecular signaling pathways and for which tumor genetic characteristics and mutations dasatinib worked best. It also provided the foundation for this new personalized medicine clinical trial.
“This is a great example of how mass spectrometry-based proteomics can identify drugs that are useful for particular types of cancer. Such studies have the promise of repurposing an existing drug for another use and therefore speeding up the development process,” said research team member John Koomen, Ph.D., director of Moffitt’s Proteomics Core Facility and member of the Molecular Oncology and Drug Discovery Program.
“Combining our efforts in proteomics with tumor profiling could produce additional insights that point toward new approaches to treating lung cancer. If our results in the new trial with dasatinib are successful, the drug could be of great benefit to thousands of patients with squamous cell lung cancer,” Haura said.
Moffitt is expanding the number of personalized genomic trials and now has trials for patients with mutations in a number of genes.
The clinical trial, in collaboration with Bristol-Myers Squibb, began on July 30. Moffitt was the first institution in the United States to enroll a patient in this trial and has since enrolled a second patient to receive the treatment.