Intrahepatic Cholangiocarcinoma: Continuing Challenges and Translational Advances

Alphonse E. Sirica, Gregory J. Gores, John Davis Groopman, Florin Selaru, Mario Strazzabosco, Xin Wei Wang, Andrew X. Zhu

Research output: Contribution to journalReview article

Abstract

Intrahepatic cholangiocarcinoma (iCCA) has over the last 10-20 years become the focus of increasing concern, largely due to its rising incidence and high mortality rates worldwide. The significant increase in mortality rates from this primary hepatobiliary cancer, particularly over the past decade, has coincided with a rapidly growing interest among clinicians, investigators, and patient advocates to seek greater mechanistic insights and more effective biomarker-driven targeted approaches for managing and/or preventing this challenging liver cancer. In addition to discussing challenges posed by this aggressive cancer, this review will emphasize recent epidemiological, basic, and translational research findings for iCCA. In particular, we will highlight emerging demographic changes and evolving risk factors, the critical role of the tumor microenvironment, extracellular vesicle biomarkers and therapeutics, intertumoral and intratumoral heterogeneity, and current and emerging targeted therapies regarding iCCA. Specifically, recent evidence linking non–bile duct medical conditions, such as nonalcoholic fatty liver disease and nonspecific cirrhosis, to intrahepatic cholangiocarcinogenesis together with geographic and ethnic variation will be assessed. Recent developments concerning the roles played by transforming growth factor-β and platelet-derived growth factor D in driving the recruitment and expansion of cancer-associated myofibroblasts within cholangiocarcinoma (CCA) stroma as well as their therapeutic implications will also be discussed. In addition, the potential significance of extracellular vesicles as bile and serum biomarkers and therapeutic delivery systems for iCCA will be described. An integrated systems approach to classifying heterogeneous iCCA subtypes will be further highlighted, and recent clinical trials and emerging targeted therapies will be reviewed, along with recommendations for future translational research opportunities. Established international CCA networks are now facilitating collaborations aimed at advancing iCCA translational and clinical research.

Original languageEnglish (US)
Pages (from-to)1803-1815
Number of pages13
JournalHepatology
Volume69
Issue number4
DOIs
StatePublished - Apr 1 2019

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Cholangiocarcinoma
Translational Medical Research
Biomarkers
Therapeutics
Neoplasms
Tumor Microenvironment
Myofibroblasts
Mortality
Platelet-Derived Growth Factor
Transforming Growth Factors
Liver Neoplasms
Systems Analysis
Bile
Fibrosis
Research Personnel
Demography
Clinical Trials
Incidence
Serum

ASJC Scopus subject areas

  • Hepatology

Cite this

Sirica, A. E., Gores, G. J., Groopman, J. D., Selaru, F., Strazzabosco, M., Wei Wang, X., & Zhu, A. X. (2019). Intrahepatic Cholangiocarcinoma: Continuing Challenges and Translational Advances. Hepatology, 69(4), 1803-1815. https://doi.org/10.1002/hep.30289

Intrahepatic Cholangiocarcinoma : Continuing Challenges and Translational Advances. / Sirica, Alphonse E.; Gores, Gregory J.; Groopman, John Davis; Selaru, Florin; Strazzabosco, Mario; Wei Wang, Xin; Zhu, Andrew X.

In: Hepatology, Vol. 69, No. 4, 01.04.2019, p. 1803-1815.

Research output: Contribution to journalReview article

Sirica, AE, Gores, GJ, Groopman, JD, Selaru, F, Strazzabosco, M, Wei Wang, X & Zhu, AX 2019, 'Intrahepatic Cholangiocarcinoma: Continuing Challenges and Translational Advances', Hepatology, vol. 69, no. 4, pp. 1803-1815. https://doi.org/10.1002/hep.30289
Sirica, Alphonse E. ; Gores, Gregory J. ; Groopman, John Davis ; Selaru, Florin ; Strazzabosco, Mario ; Wei Wang, Xin ; Zhu, Andrew X. / Intrahepatic Cholangiocarcinoma : Continuing Challenges and Translational Advances. In: Hepatology. 2019 ; Vol. 69, No. 4. pp. 1803-1815.
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