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Autocrine and Paracrine Mechanisms Promoting Chemoresistance in Cholangiocarcinoma

School of Medicine and Surgery, University of Milan-Bicocca, 20900 MB Monza, Italy
International Center for Digestive Health (ICDH), University of Milan-Bicocca, 20900 MB Monza, Italy
Digestive Disease Section, Yale University School of Medicine, New Haven, CT 06520, USA
The School of Medicine, Royal Derby Hospital, University of Nottingham, Derby DE22 3NE, UK
Department of Molecular Medicine, University of Padova School of Medicine, 35131 PD Padova, Italy
Author to whom correspondence should be addressed.
Academic Editor: Anthony Lemarié
Int. J. Mol. Sci. 2017, 18(1), 149;
Received: 14 November 2016 / Revised: 19 December 2016 / Accepted: 6 January 2017 / Published: 13 January 2017
(This article belongs to the Collection Programmed Cell Death and Apoptosis)
PDF [714 KB, uploaded 13 January 2017]


Resistance to conventional chemotherapeutic agents, a typical feature of cholangiocarcinoma, prevents the efficacy of the therapeutic arsenal usually used to combat malignancy in humans. Mechanisms of chemoresistance by neoplastic cholangiocytes include evasion of drug-induced apoptosis mediated by autocrine and paracrine cues released in the tumor microenvironment. Here, recent evidence regarding molecular mechanisms of chemoresistance is reviewed, as well as associations between well-developed chemoresistance and activation of the cancer stem cell compartment. It is concluded that improved understanding of the complex interplay between apoptosis signaling and the promotion of cell survival represent potentially productive areas for active investigation, with the ultimate aim of encouraging future studies to unveil new, effective strategies able to overcome current limitations on treatment. View Full-Text
Keywords: liver cancer; tumor reactive stroma; cancer stem cells; morphogens; apoptosis liver cancer; tumor reactive stroma; cancer stem cells; morphogens; apoptosis

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Cadamuro, M.; Brivio, S.; Spirli, C.; Joplin, R.E.; Strazzabosco, M.; Fabris, L. Autocrine and Paracrine Mechanisms Promoting Chemoresistance in Cholangiocarcinoma. Int. J. Mol. Sci. 2017, 18, 149.

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