Fig. 4.

Selective deletion of cancer-associated fibroblasts (CAFs) from cholangiocarcinoma (CCA) tumor microenvironment. Cancer-associated fibroblasts produce factors that promote survival of tumor cells. Cancer-associated fibroblasts are primed or sensitized for apoptosis and hence can be selectively targeted by BH3 mimetics such as navitoclax and ABT-199. Cholangiocarcinoma cells overexpress Mcl-1, which does not bind navitoclax, and hence are not a direct target of navitoclax. However, CAF deletion from the tumor microenvironment leads to secondary cancer cell death due to loss of CAF-mediated prosurvival signals.⁷⁵