The disease, called cholangiocarcinoma, has few treatment options and a five-year survival rate of less than 2% for patients with advanced disease. A new group of drugs called FGFR inhibitors offers a promising new treatment for the disease, but tumors can develop resistance to the agents, rendering them ineffective.
In this study, OSUCCC – James researchers describe secondary gene mutations — those that arise during treatment and were not present in the original primary tumor — that caused resistance to an FGFR inhibitor that had initially helped the patient. They also showed that the acquired mutations occurred in subgroups of tumor cells that arose within the metastatic tumors.
“Our results demonstrate the emergence of drug-resistance mutations in subgroups of tumor cells from a patient with cholangiocarcinoma,” says Melanie Krook, PhD, senior postdoctoral researcher at the OSUCCC – James and first author of the paper.
About 20% of patients with this bile duct cancer have mutations in FGFR genes. The mutated genes contribute to tumor development. FGFR inhibitors are designed to block the effects of the mutated genes.
“Ten FGFR inhibitors are in development, and it’s critically important for us to understand how cancer cells develop resistance to them,” says Sameek Roychowdhury, MD, PhD, associate professor in the Division of Medical Oncology at Ohio State and senior author of the study. Roychowdhury also is in the Translational Therapeutics Program at the OSUCCC – James.
This research was conducted through a Body Donation for Cancer Research study at the OSUCCC – James that allows patients to donate their organs and tissue for cancer research after death. Those interested in learning more about supporting this study can contact Jamesline@osumc.edu.
“Studying how drug resistance develops is challenging, since it is hard to study every tumor in a person’s body. We were able to make this discovery because the patient had consented to an organ donation and research autopsy, which can yield unprecedented insights into how cancer evolves and changes during the course of the disease. We are so grateful to our patients and hope to honor their support through research that can help others,” Roychowdhury adds.
Published in the journal Molecular Case Studies.