Liver cancer is the most common cancer worldwide and in Thailand (Srivatanakul, 2001) and primary cancer of the liver comprising of both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), is the leading cancer of males and third in frequency in females (Srivatanakul, 2001). Cholangiocarcinoma, a lethal cancer of the epithelial cells lining the biliary tract, is the second most common type of primary liver cancer with the highest incidence rate in the Northeast Thailand. The major risk factors of this cancer associate with chronic inflammatory of the bile duct, primary sclerosing cholangiotis, hepatolithiasis and liver fluke (Opisthorchis viverrini) infection. This type of cancer is associated with poor prognosis and limited treatment options due to the late clinical presentation of the advanced disease. Surgical resection is the best option for CCA patients, however, not all patients are capable of surgery depending on the site of cancer within the liver or the biliary tract (Khan et al., 2012). In addition, adjuvant radiotherapy and chemotherapy have not been shown to substantially improve survival in CCA patients with or without surgery (Anderson, Pinson, Berlin, & Chari, 2004; Hezel & Zhu, 2008). Resistance to chemotherapeutic drugs such as alterations in the drug target, activation of prosurvival pathways and ineffective induction of cell death, is the major obstacle to cancer treatment, including CCA (Holohan, Van Schaeybroeck, Longley, & Johnston, 2013). Therefore, understanding the mechanism of resistance is important to improve chemotherapy treatment.

      Although surgery resection is the major method to cure CCA, not all patients are qualified for complete surgical resection due to the stage of the disease. Therefore, chemotherapy treatments are necessary to improve patient quality of life and survival. 5-FU and 5-FU-based regimens were among the first to use in biliary tract cancer (Hezel & Zhu, 2008). Gemcitabine, a nucleotide analogue, is widely used alone and in combination with other therapeutic agents such as cisplatin (Eckel & Schmid, 2007; Giuliani et al., 2006) and 5-FU (Alberts et al., 2005) which offer a slight advantage over other regimens (Eckel & Schmid, 2007).

      Chemoresistance is the major problem of using anticancer drug to treat cancer. The mechanism of resistance involves multifactorial processes including alterations of drug targets, drug efflux, drug inactivation, activation of prosurvival pathway, and inefficient of apoptosis (cell death) induction (Holohan et al., 2013). Most of anticancer agents induce DNA damage to cancer cells and these cells response to the damage by inducing cell death or apoptosis machinery (Fodale, Pierobon, Liotta, & Petricoin, 2011). However, an increase of DNA repair capacity impairs the ability of genotoxic drugs to induce cancer cell death. Upregulation of DNA repair proteins is one of the chemoresistance mechanisms. To improve chemotherapeutic treatment, it is needed to gain more knowledge on the DNA damage response and DNA repair mechanism in cancer cells after treatment with genotoxic anticancer drug.