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Published on: January 12, 2020
Role of the Notch signaling in cholangiocarcinoma
Antonio Cigliano1, Jingxiao Wang2,3, Xin Chen3
1a Institut für Pathologie , Universitätsmedizin Greifswald , Greifswald , Germany.
Introduction:
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.
Insights
Cholangiocarcinoma (CCA) is a liver cancer driven by the Notch pathway. Targeting this pathway shows promise for new cholangiocarcinoma treatments.
Area of Science:
- Hepatobiliary cancers
- Molecular oncology
- Cancer signaling pathways
Background:
- Cholangiocarcinoma (CCA) is an aggressive liver cancer with poor prognosis.
- CCA exhibits resistance to standard chemotherapy.
- The Notch signaling pathway is implicated in liver cancer development and progression.
Purpose of the Study:
- To review the current understanding of the Notch pathway in cholangiocarcinogenesis.
- To discuss therapeutic strategies targeting Notch signaling in CCA.
- To evaluate preclinical trial outcomes for Notch-targeted therapies.
Main Methods:
- Comprehensive literature review of Notch pathway in CCA.
- Analysis of molecular mechanisms and signaling crosstalk.
- Evaluation of preclinical data for therapeutic interventions.
Main Results:
- The Notch pathway is a critical driver of CCA development and aggressiveness.
- Targeting Notch signaling has shown encouraging results in preclinical studies.
- Understanding Notch pathway crosstalk is key for novel therapy design.
Conclusions:
- The Notch pathway is a significant driver of human CCA and a promising therapeutic target.
- Further research into Notch pathway mechanisms and interactions will guide innovative CCA therapies.
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