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YAP and the Hippo pathway in cholangiocarcinoma.


ABSTRACT: Cholangiocarcinoma (CCA) has an increasing incidence and remains a difficult to treat malignancy. In a search for more effective treatment options, progress has been made in identifying molecular drivers of oncogenic signaling including IDH mutations and FGFR2 fusions. In addition, multiple investigators have identified increased activity of YAP, the effector protein of the Hippo pathway, in CCA. The Hippo pathway regulates organ size, cellular proliferation, and apoptosis via YAP, a transcriptional co-activator. Targeting of the pathway has been difficult due the lack of a dedicated cell-surface receptor. However, more recently, additional cross-regulatory pathways have been identified that are potentially targetable. In this review, we address the current treatment landscape for CCA, the Hippo pathway broadly, animal models of CCA with attention to Hippo-related models, and the current strategies for targeting YAP.

SUBMITTER: Sugihara T 

PROVIDER: S-EPMC6536462 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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YAP and the Hippo pathway in cholangiocarcinoma.

Sugihara Takaaki T   Isomoto Hajime H   Gores Gregory G   Smoot Rory R  

Journal of gastroenterology 20190227 6


Cholangiocarcinoma (CCA) has an increasing incidence and remains a difficult to treat malignancy. In a search for more effective treatment options, progress has been made in identifying molecular drivers of oncogenic signaling including IDH mutations and FGFR2 fusions. In addition, multiple investigators have identified increased activity of YAP, the effector protein of the Hippo pathway, in CCA. The Hippo pathway regulates organ size, cellular proliferation, and apoptosis via YAP, a transcripti  ...[more]

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