John V. Heymach, MD, PhD, and colleagues have been awarded a research grant from LUNGevity Foundation to develop better predictive biomarkers and treatment protocols for non-small cell lung cancer patients.
Dr. Heymach, Associate Professor in the Department of Thoracic/Head and Neck Medical Oncology and in the Department of Cancer Biology at The University of Texas MD Anderson Cancer Center, is collaborating on this project with David Carbone, MD, PhD, who is now Director of the Thoracic Center at Ohio State University.
Drugs targeting tumor blood vessels, such as bevacizumab and other inhibitors of the vascular endothelial growth factor (VEGF) pathway, improve survival rates for patients with non-small cell lung cancer. However, not all patients should undergo this treatment. In some patients the drugs don’t seem to have any effect, whereas in others they can cause life-threatening illness. Plus, the benefits are often short-lived, as almost all non-small cell lung cancer tumors eventually become resistant to the drugs.
This funding will help investigators apply a multipronged approach to identify patients who are most likely to benefit from a VEGF inhibitor and to spare patients who are unlikely to see an improvement. In addition, the grantees hope to gain critical insights into the mechanisms of drug resistance that can guide future lung cancer treatment.
“Medicine shouldn’t make people sicker. We are using all the tools at our disposal to develop a test that improves the quality of patient care and allows more personalized medicine,” says Dr. Heymach. “We also hope to contribute to understanding how drug resistance can be overcome. After all, knowledge is power.”
The three complementary approaches funded by this grant use different technologies to help develop a blood test to determine which patients will benefit from VEGF inhibitors. All three approaches are based on comparing blood samples from patients who responded well to VEGF inhibitor treatment to blood samples from patients who did not respond well to this treatment.
One approach considers the patients’ genetics. The investigators are comparing single nucleotide polymorphisms, minute changes in the genetic code, from the blood samples. The goal is to identify a signature combination of genetic changes within three key genes that would predict a high likelihood of success with VEGF treatment.
The other two approaches study specific proteins. Because both the patient overall and the tumor itself secrete proteins, these approaches require a great deal of careful analysis. The investigators are applying two parallel techniques to profile and identify proteins in the blood samples that would forecast positive results with VEGF inhibitor treatment.
By culling the best biomarkers from these three approaches, the investigators will confirm the relevance of the most promising biomarkers in two independent, randomized trials. Once the trials are complete, this work could revolutionize the treatment of patients with non-small cell lung cancer by providing a simple blood test to determine if a VEGF inhibitor would be a good treatment choice.