Protein Kinases as Targets for Opisthorchis viverrini- Associated Cholangiocarcinoma Therapy

Abstract

Protein kinases are enzymes that catalyze the transfer of phosphate from ATP to the serine/threonine or tyrosine residues of target molecules. These are key important mediators in a signaling cascade involved in several biological processes. Dysregulation of their activity has been found in various tumors. From the increased understanding of kinase structure and activation mechanisms emerged new strategies for targeting kinase in cancer treatment. Nowadays, kinase specific inhibitors are developed and widely used for clinical cancer treatment. In this review, we focus on protein kinases that are involved in cholangiocarcinoma (CCA). CCA is a slow progression tumor that is recognized as a major public health issue in northeastern Thailand. The standard regimen for CCA treatment is surgical resection. However, the patient's clinical outcome is still problematic. Therefore, the search to identify molecular mechanisms and molecules that are involved in carcinogenesis and the progression of CCA that can be used as therapeutic targets is urgently required. Aberrant expression and activation, as well as the functions of protein kinases in CCA, have been extensively studied in order to apply them as therapeutic targets. This review provides the information on protein kinases and their activity in CCA, as well as the preclinical data on kinase inhibitors that have been evaluated for this cancer.

Keywords: Protein kinases; cholangiocarcinoma (CCA); cholangiocarcinoma therapy; kinase inhibitors; signal transduction; targeted therapy.