Targeting Cholangiocarcinoma with drugs that regulate epigenetic mechanisms of tumour survival (360G-Wellcome-207247_Z_17_Z)

Cholangiocarcinoma (CCA), a malignant transformation of cholangiocytes, the epithelial cells lining the biliary tract. CCA has a poor prognosis with a high mortality rate as a consequence of a poor understanding of the molecular biology of the cholangiocyte transformation, and a consequent lack of effective drug therapies. CCA progresses with unspecific, invasive and silent symptoms, and is usually diagnosed in the advanced stages. Surgery represents the only curative treatment for CCA and has a high rate of recurrence. Chemotherapy and radiation therapies have been used in an attempt to control this cancer and improve the survival of patients with advanced CCA. However, these therapeutic strategies are not effective in prolonging long-term survival. Inhibiting epigenetic regulation of gene expression has gained momentum as a method of targetting tumours as it can inhibit the expression of multiple oncogenes and repression of multiple tumour suppressor genes at once. Epigenetic inhibitors are in several stages of clinical trails for other cancers however the study of epigenetics in cholangiocarcinoma is limited. The hypothesis of the study is epigenetic inhibitors that are effective at targeting other solid tumours will induce apoptosis and growth arrest, and reduce the expression of oncogenes in cholangiocarcinomas.