Dual targeting of G9a and DNMT1 for the treatment of experimental cholangiocarcinoma

Cholangiocarcinoma (CCA) is a devastating disease often detected at advanced stages when surgery cannot be performed. Conventional and targeted systemic therapies perform poorly and therefore effective drugs are urgently needed. Different epigenetic modifications occur in CCA and contribute to malignancy. Targeting epigenetic mechanisms may thus open new therapeutic opportunities. However, modifications such as DNA and histone methylation often co-exist and cooperate in carcinogenesis. We tested the therapeutic efficacy and mechanism of action of a new class of dual G9a histone-methyltransferase and DNA-methyltransferase 1 (DNMT1) inhibitors.