Molecular Targeted Therapy of Biliary Tract Cancer – Results of the First Clinical Studies

Marcus      W. Wiedmann; Joachim      Mossner

Abstract

Carcinoma of the biliary tree are rare tumors of the gastrointestinal tract with worldwide rising incidence for intrahepatic cholangiocarcinoma during the last years. Although complete surgical resection is the only curative approach, this can be accomplished in a minority of patients, since most of them present with advanced disease. In addition, those patients who have undergone complete surgical resection experience a high tumor recurrence rate. Non-resectable biliary tract cancer is associated with a poor prognosis due to wide resistance to chemotherapeutic agents and radiotherapy. It is therefore essential to search for new therapeutical approaches. After several years of preclinical research, the first clinical study data are now available for this tumor entity. Inhibitors of the epidermal growth factor receptor (EGFR) family, such as erlotinib, cetuximab, and lapatinib were recently investigated. Furthermore, bortezomib, an inbibitor of the proteasome, imatinib mesylate, an inhibitor of c-kit-R, bevacizumab, an inhibitor of vascular endothelial growth factor (VEGF), and sorafenib (BAY 43-9006), a multiple kinase inhibitor that blocks not only receptor tyrosine kinases but also serine/threonine kinases along the RAS/RAF/MEK/ERK pathway, were studied, as well. Although early evidence of antitumor activity was seen, the results are still preliminary and require further investigations.

Keywords: Bile duct cancer, cholangiocarcinoma, molecular targeted therapy, tyrosine kinase inhibitor

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