Cholangiocarcinoma (CCA) is the second most common primary liver cancer, after hepatocellular carcinoma (HCC), and the incidence is increasing worldwide. The high mortality of CCA is due to its aggressiveness, late diagnosis and refractory nature. Our preliminary results indicate that c-Jun N-terminal protein kinases (JNK) play a crucial role in the malignant transformation of liver cells and, therefore, in CCA initiation and progression. In addition, overexpression of the epidermal growth factor receptor (EGFR) family - including HER2/ErbB2 proteins - appears to induce such transformation. Using experimental models and cell lines, in this innovative research project we intend not only to open new therapeutic avenues, but also to evaluate the efficacy of EGFR/HER2 blockade in CCA development.