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Challenges and opportunities in the clinical development of immune checkpoint inhibitors for hepatocellular carcinoma

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Title: Challenges and opportunities in the clinical development of immune checkpoint inhibitors for hepatocellular carcinoma
Authors: Flynn, MJ
Sayed, AA
Sharma, R
Siddique, A
Pinato, DJ
Item Type: Journal Article
Abstract: After a decade of stagnation in drug development, therapeutic reversal of immune-exhaustion with immune checkpoint inhibitors (ICPI) has been shown to be effective in advanced hepatocellular carcinoma (HCC). The clinical development of novel ICPIs continues at a rapid pace, with more than 50 clinical trials of immunotherapeutic agents registered as of May 2018 for this indication. The development of ICPI is particularly challenging in patients with HCC, a population with unique features which impact on safety and efficacy of immune-modulating therapies. In this review, we discuss the biologic foundations supporting the development of ICPI across the advancing stages of HCC, focusing in particular on the proposal of a rational positioning of ICPI across the various Barcelona-Clinic Liver Cancer stages of the disease. Translational studies should guide adequate prioritisation of those therapeutic agents and combination strategies which are most likely to achieve patient benefit based on solid mechanistic and clinical justifications. This article is protected by copyright. All rights reserved.
Issue Date: 1-Nov-2018
Date of Acceptance: 1-Nov-2018
URI: http://hdl.handle.net/10044/1/64117
DOI: https://dx.doi.org/10.1002/hep.30337
ISSN: 0270-9139
Publisher: Wiley
Journal / Book Title: Hepatology
Copyright Statement: © 2018 American Association for the Study of Liver Diseases. This is the accepted version of the following article: Flynn, M. J., Sayed, A. A., Sharma, R. , Siddique, A. and Pinato, D. J. (2018), Challenges and opportunities in the clinical development of immune checkpoint inhibitors for hepatocellular carcinoma. Hepatology., which has been published in final form at https://dx.doi.org/10.1002/hep.30337
Sponsor/Funder: Cancer Research UK
Funder's Grant Number: C57701/A26137
Keywords: antiangiogenics
biomarkers
cirrhosis
hepatocellular carcinoma
immune-checkpoint inhibitors
loco-regional therapies
1103 Clinical Sciences
1101 Medical Biochemistry And Metabolomics
Gastroenterology & Hepatology
Publication Status: Published online
Conference Place: United States
Embargo Date: 2019-11-01
Online Publication Date: 2018-11-01
Appears in Collections:Division of Surgery
Division of Cancer
Faculty of Medicine



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