Role of the Notch signaling in cholangiocarcinoma.
Cholangiocarcinoma (CCA) is an emerging cancer entity of the liver, associated with poor outcome and characterized by resistance to conventional chemotherapeutic treatments. In the last decade, many signaling pathways associated with CCA development and progression have been identified and are currently under intense investigation. Cumulating evidence indicates that the Notch cascade, a highly-conserved pathway in most multicellular organisms, is a critical player both in liver malignant transformation and tumor aggressiveness, thus representing a potential therapeutic target in this pernicious disease. Areas covered: In the present review article, we comprehensively summarize and critically discuss the current knowledge on the Notch pathway, its specific and key roles in cholangiocarcinogenesis, the treatment strategies aimed at suppressing this signaling cascade in cancer, and the encouraging results coming from preclinical trials. Expert opinion: The Notch pathway represents a major driver of carcinogenesis and a promising therapeutic target in human CCA. A better understanding of the molecular mechanisms triggered by the Notch pathway as well as its functional crosstalk with other signaling cascade will be highly helpful for the design of innovative therapies against human CCA.
a Institut für Pathologie , Universitätsmedizin Greifswald , Greifswald , Germany.
Antonio
A
Cigliano
b Second Clinical Medical School , Beijing University of Chinese Medicine , Beijing , China.|c Department of Bioengineering and Therapeutic Sciences and Liver Center , University of California , San Francisco , CA , USA.
Jingxiao
J
Wang
c Department of Bioengineering and Therapeutic Sciences and Liver Center , University of California , San Francisco , CA , USA.
Xin
X
Chen
a Institut für Pathologie , Universitätsmedizin Greifswald , Greifswald , Germany.
Diego F
DF
Calvisi
D000818:Animals; D001650:Bile Duct Neoplasms / Q000503:physiopathology* / Q000628:therapy; D018281:Cholangiocarcinoma / Q000503:physiopathology* / Q000628:therapy; D018450:Disease Progression; D006801:Humans; D058990:Molecular Targeted Therapy; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction
D051880:Receptors, Notch
Notch signaling; cholangiocarcinoma; preclinical models; targeted therapies