“Cholangiocarcinomas are devastating cancers of intrahepatic and extrahepatic origin that are increasing in both their worldwide incidence and mortality rates.
Conventional chemotherapy and radiation therapy are not effective in prolonging long-term survival; therefore it is important to understand the cellular mechanisms of cholangiocarcinoma cell growth with a view to develop novel chemopreventive strategies.
We have recently demonstrated that the endocannabinoids anandamide (AEA) and 2-arachidonyl glycerol (2-AG) exert opposing effects on cholangiocarcinoma cell growth in vitro via cannabinoid receptor-independent mechanisms.
AEA increased presenilin 1 expression and recruitment into the γ-secretase complex whereas 2-AG increased expression and recruitment of presenilin 2.
The development of novel therapeutic strategies aimed at modulating the endocannabinoid system, or mimicking the mode of action of AEA on Notch signaling pathways would prove beneficial for cholangiocarcinoma management.
We propose that the development of novel therapeutic strategies aimed at modulating the endocannabinoid system, or mimicking the mode of action of AEA on Notch signaling pathways would prove beneficial for the treatment of this devastating disease.”
