Tumor Heterogeneity and Drug Resistance in Cholangiocarcinoma

Cholangiocarcinoma is a rare and aggressive tumor of the bile ducts with a median survival of less than one year. It affects approximately 8,000-10,000 new people each year. The discovery of mutations in the metabolic gene IDH1 in 20% of patients and FGFR2 fusions in 15% of patients with intrahepatic cholangiocarcinoma has the potential to be a gamechanger for these patients. While IDH1 inhibitors and FGFR inhibitors have shown some benefit, they have not been the home run we have hoped for. Several patients do not respond to the drugs despite having the target, and several other patients progress after only 3 to 6 months on therapy. A major reason for this drug failure is tumor heterogeneity, or the presence of mixed populations of sensitive and resistant clones.

Dr. Lipika Goyal MD, MPhil is a recognized expert in IDH1 and FGFR2 mutant cholangiocarcinoma, having helped develop drugs that are slated to gain FDA approval for these cancers in 2021. She would now like to study how we can make these drugs work for more patients and also prolong responses in those for whom they’re already working. Dr. Goyal has developed a large tissue repository, the Cholangiocarcinoma Biobank, and a world class collection of patient-derived laboratory models with her collaborators, and these will serve as a ready resource to catapult these studies forward.