<qa>  What is the potential explanation for the tropism exerted by CCA?The growing understanding of the molecular pathogenesis of CCA opens new therapeutic options for molecular targeting Blechacz and Gores 2008. In particular EGFR signaling appears to be important for tumor growth of CCA. Inhibition of EGFR signaling has been shown to significantly suppress CCA cell growth Blechacz and Gores 2008. In addition EGFR can directly be activated by bile acids and promote CCA cell proliferation, a potential explanation for the tropism exerted by CCA for the biliary tree. It has been shown that EGFR activation is sustained in CCA by failure to internalize the ligand-receptor complex, a homeostatic mechanism essential for receptor inactivation. EGFR phosphorylation results in activation of the downstream kinases p4244 MAPK and p38 MAPK, which in turn increase cyclooxygenase 2 expression in CCA cells. 