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Review

Molecular Mechanisms Linking Risk Factors to Cholangiocarcinoma Development

1
Hepatology and Gastroenterology Division, Department of Medicine, Indiana University, Indianapolis, IN 46202, USA
2
Unit of Hepatology, Tor Vergata University, 00133 Rome, Italy
3
Department of Research, Richard L. Roudebush VA Medical Center, Indianapolis, IN 46202, USA
4
Department of Surgery, Division of Transplant Surgery, Indiana University, Indianapolis, IN 46202, USA
5
Department of Nutrition, Texas A&M University, College Station, TX 77843, USA
6
Department of Medical Physiology, Texas A&M University College of Medicine, Bryan, TX 77807, USA
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editors: Alessandro Granito and Lorenza Rimassa
Cancers 2022, 14(6), 1442; https://doi.org/10.3390/cancers14061442
Received: 16 February 2022 / Revised: 8 March 2022 / Accepted: 9 March 2022 / Published: 11 March 2022
(This article belongs to the Special Issue Feature Paper from Journal Reviewers)
Cholangiocarcinoma is the second most frequent primary liver tumor in humans. In this review, we report current findings on the mechanisms linking well-known risk factors to this cancer. These pathways may be in part involved in risk factors unrelated to cholangiocarcinoma forms.
The poor prognosis of cholangiocarcinoma in humans is related to several factors, such as (i) the heterogeneity of the disease, (ii) the late onset of symptoms and (iii) the limited comprehension of the carcinogenic pathways determining neoplastic changes, which all limit the pursuit of appropriate treatment. Several risk factors have been recognized, including different infective, immune-mediated, and dysmorphogenic disorders of the biliary tree. In this review, we report the details of possible mechanisms that lead a specific premalignant pathological condition to become cholangiocarcinoma. For instance, during liver fluke infection, factors secreted from the worms may play a major role in pathogenesis. In primary sclerosing cholangitis, deregulation of histamine and bile-acid signaling may determine important changes in cellular pathways. The study of these molecular events may also shed some light on the pathogenesis of sporadic (unrelated to risk factors) forms of cholangiocarcinoma, which represent the majority (nearly 75%) of cases. View Full-Text
Keywords: cholangiocarcinoma; risk factor; liver fluke; primary sclerosing cholangitis; bile duct cysts; cirrhosis cholangiocarcinoma; risk factor; liver fluke; primary sclerosing cholangitis; bile duct cysts; cirrhosis
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MDPI and ACS Style

Ceci, L.; Zhou, T.; Lenci, I.; Meadows, V.; Kennedy, L.; Li, P.; Ekser, B.; Milana, M.; Zhang, W.; Wu, C.; Sato, K.; Chakraborty, S.; Glaser, S.S.; Francis, H.; Alpini, G.; Baiocchi, L. Molecular Mechanisms Linking Risk Factors to Cholangiocarcinoma Development. Cancers 2022, 14, 1442. https://doi.org/10.3390/cancers14061442

AMA Style

Ceci L, Zhou T, Lenci I, Meadows V, Kennedy L, Li P, Ekser B, Milana M, Zhang W, Wu C, Sato K, Chakraborty S, Glaser SS, Francis H, Alpini G, Baiocchi L. Molecular Mechanisms Linking Risk Factors to Cholangiocarcinoma Development. Cancers. 2022; 14(6):1442. https://doi.org/10.3390/cancers14061442

Chicago/Turabian Style

Ceci, Ludovica, Tianhao Zhou, Ilaria Lenci, Vik Meadows, Lindsey Kennedy, Ping Li, Burcin Ekser, Martina Milana, Wenjun Zhang, Chaodong Wu, Keisaku Sato, Sanjukta Chakraborty, Shannon S. Glaser, Heather Francis, Gianfranco Alpini, and Leonardo Baiocchi. 2022. "Molecular Mechanisms Linking Risk Factors to Cholangiocarcinoma Development" Cancers 14, no. 6: 1442. https://doi.org/10.3390/cancers14061442

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