The findings of a study published in the journal Molecular Cancer Therapeutics exhibits how resistance to a promising targeted drug develops in patients with cholangiocarcinoma, a rare and deadly form of bile duct cancer. The study also showed that adding an FGFR inhibitor may re-sensitize tumor cells to the initial treatment.
“While the majority of patients with FGFR-positive cholangiocarcinoma benefit from new FGFR inhibitors in clinical trials, most patients unfortunately develop cancers resistant to the drugs,” says study leader Sameek Roychowdhury, MD, PhD, a medial oncologist and researcher at the OSUCCC – James in a press release. “We believe that this study is an important step in understanding drug resistance and improving the treatment of this and other cancers caused by abnormal FGFR gene mutations.”
In this study, the researchers assessed the FGFR (fibroblast growth factor receptor) gene in the cancer cells of a cholangiocarcinoma patient who died after experiencing disease progression and developing resistance to the FGFR inhibitor infigratinib.
According to the results, researchers observed two acquired FGFR mutations in the patient’s tumor cells that conferred resistance to FGFR inhibitors. They then used cancer cell lines to learn that the mutations led to activation of the mTOR biochemical pathway. This enabled the cancer cells to grow even in the presence of FGFR inhibitors. They discovered that adding a mTOR inhibitor to the cells restored their sensitivity to FGFR inhibitors.
“A better understanding of how treatment resistance develops and how to prevent it is critical for improving the treatment of cholangiocarcinoma and other cancers caused by FGFR mutations,” says first author Melanie Krook, PhD, a postdoctoral fellow in Roychowdhury’s lab.
Study suggests new strategy for treating advanced, progressing bile duct #cancer https://t.co/owdsi1Zsuu
— Medical Xpress (@medical_xpress) January 14, 2020
Dr. Krook added that: “Our findings suggest that cholangiocarcinoma patients treated with an FGFR targeted therapy could potential benefit from combination therapies with other drugs such as mTOR inhibitors. Additional laboratory studies are needed to identify the optimal lead strategies for this combination.”
A new study led by researchers at The Ohio State University Comprehensive Cancer Center suggests new strategy for treating advanced, progressing bile duct cancer https://t.co/2jIZipelVO
— Art Fridrich (@Ahighervision) January 14, 2020
Study suggests new strategy for treating advanced, progressing bile duct cancer https://t.co/eGJEmd9rpJ
— Cancer Research News (@CancerStudyNews) January 15, 2020