The identification of molecular markers to guide treatment decisions for patients with advanced disease is extremely important, according to senior author Laura J. Niedernhofer, M.D., Ph.D., associate professor of microbiology and molecular genetics, University of Pittsburgh School of Medicine.
Her team examined the role of ERCC1-XPF, an enzyme that prevents genetic mutations and cancer because of its role in DNA repair. But many commonly used platinum-based chemotherapy agents kill cancer cells by damaging their DNA, so the enzyme’s presence could work against such drugs.
“These chemotherapies are quite toxic, so if we can identify which patients will respond before treatment begins, we can hopefully improve the quality of life for the rest of the patient population by selecting alternative treatments,” Dr. Niedernhofer said.
The levels of ERCC1-XPF in a tumor could reflect whether it will be sensitive or resistant to certain chemotherapies, but according to Dr. Niedernhofer’s findings, the current standard method of measuring the enzyme isn’t accurate.
“Through the methods we developed in this study, we determined first that ERCC1-XPF protein levels vary from tumor to tumor. We also created the first rigorous approach for identifying biomarkers that could help determine which patients might benefit from certain chemotherapies, and which patients might not,” said Dr. Niedernhofer.
In their study, the team critically evaluated the specificity of antibodies used to measure ERCC1-XPF in tumors. Their results showed the typically used antibody isn’t as well suited to gauging enzyme levels in tissue samples as are other available antibodies. The study provides reliable tools for clinicians to measure the enzyme biomarker in clinical specimens, and illustrates a strategy for the measurement of other antibodies against potential biomarkers that could help stratify patients according to cancer risk, response to treatment and overall prognosis.
Co-authors of the paper include Nikhil R. Bhagwat, Vera Y. Roginskaya, Marie B. Acquafondata, and Rajiv Dhir, M.D., all of the University of Pittsburgh School of Medicine; and Rick Wood, Ph.D., now of MD Anderson Cancer Center.
The study was funded by the University of Pittsburgh Cancer Institute SPORE grant for Lung Cancer Research.
Founded in 1984, the University of Pittsburgh Cancer Institute became a National Cancer Institute (NCI) -designated Comprehensive Cancer Center in 1990. UPCI, the only cancer center in western Pennsylvania with this elite designation, serves the region’s population of more than 6 million. Presently, UPCI receives a total of $154 million in research grants and is ranked 10th in funding from the NCI.