Dr. Sia on a Novel Classification System in Intrahepatic Cholangiocarcinoma

Daniela Sia, PhD, assistant professor, Division of Liver Diseases, Department of Medicine, Tisch Cancer Institute, Icahn School of Medicine, Mount Sinai, discusses a novel microenvironment-based classification system of intrahepatic cholangiocarcinoma.

Based on the research, 5 novel stroma tumor immune (STIM)-based classes with different immune composition were identified in intrahepatic cholangiocarcinoma, Sia explains. Each class also incorporates different immune cells and different structural aberrations, Sia notes. One class had enrichment in IDH1/2 mutations and FGFR2 fusions, which is relevant because they can be targeted. Moreover, in intrahepatic cholangiocarcinoma, monotherapies do not provide significant efficacy. Although it is possible to block FGFR, resistance mechanisms arise, creating a need to further block FGFR through the microenvironment, Sia says.

This classification system provides additional information on how the different tumor cells may interact with other elements in intrahepatic cholangiocarcinoma. Next steps should be to block structural variation of the tumor by combining targeted therapies with immunotherapies, Sia continues.

Additionally, it is important to learn in terms of how KRAS mutations can shape the tumor macroenvironment, which will make it possible to design rational combination strategies, Sia says. Recently, there wasanother KRAS inhibitor was tested in combination with PD-L1 therapy, demonstrating significant responses. This is a sign that the algorithim applied allowed the field to learn about the tumor microenvironment and how it can be used to inform and design other combination approaches, Sia concludes.