Lung Cancer Study Reveals New Drug Combination Targets

Editor’s note: Oncologists often prescribe lung cancer treatments based on specific proteins found in patients’ tumors. These treatments are known as targeted therapies. This article describes how a patient with an unexpected response to treatment contributed to new research into targeted therapies. This patient responded exceptionally well to a drug that targets a protein called IGF-1R. She was found to have a mutation in the ALK protein, and was then successfully treated with the ALK-targeted drug crizotinib. Based on her success, researchers hope that combining an IGF-1R-targeted drug with crizotinib could help treat other patients with ALK mutations.

“A Vanderbilt lung cancer patient’s exceptional response to different types of therapies spurred research that suggests lung cancer patients with specific gene alterations may benefit from combination therapy that targets two different cancer pathways.

The study, led by Christine Lovly, M.D., Ph.D., assistant professor of Medicine and Cancer Biology, was published online in Nature Medicine.

The work was based on an intriguing clinical observation of a female patient with advanced lung cancer who had an unexpected response to a monoclonal antibody that targets the insulin-like growth factor receptor (IGF-1R). IGF-1R helps cancer cells survive and evade anti-cancer therapies.

Remarkably, the patient remained on the IGF-1R therapy for 17 months – far longer than any other patient on the clinical trial. The Vanderbilt researchers, led by Lovly, became interested in why this particular patient’stumor responded to the experimental therapy so dramatically. Investigators decided to test for gene mutations and found an unexpected result – the patient’s tumor was positive for an ALK gene fusion. Only about 5 percent of lung cancer patients have this gene fusion in their tumor.