Advances in targeted therapies for hepatocellular carcinoma in the genomic era

Llovet, Josep M; Villanueva, Augusto; Lachenmayer, Anja; Finn, Richard S (2015). Advances in targeted therapies for hepatocellular carcinoma in the genomic era. Nature reviews - clinical oncology, 12(7), pp. 408-424. Nature Publishing Group 10.1038/nrclinonc.2015.103

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Mortality owing to liver cancer has increased in the past 20 years, and the latest estimates indicate that the global health burden of this disease will continue to grow. Most patients with hepatocellular carcinoma (HCC) are still diagnosed at intermediate or advanced disease stages, where curative approaches are often not feasible. Among the treatment options available, the molecular targeted agent sorafenib is able to significantly increase overall survival in these patients. Thereafter, up to seven large, randomized phase III clinical trials investigating other molecular therapies in the first-line and second-line settings have failed to improve on the results observed with this agent. Potential reasons for this include intertumour heterogeneity, issues with trial design and a lack of predictive biomarkers of response. During the past 5 years, substantial advances in our knowledge of the human genome have provided a comprehensive picture of commonly mutated genes in patients with HCC. This knowledge has not yet influenced clinical decision-making or current clinical practice guidelines. In this Review the authors summarize the molecular concepts of progression, discuss the potential reasons for clinical trial failure and propose new concepts of drug development, which might lead to clinical implementation of emerging targeted agents.

Item Type:

Journal Article (Review Article)

Division/Institute:

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Visceral Surgery
04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine

UniBE Contributor:

Lachenmayer, Anja

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1759-4782

Publisher:

Nature Publishing Group

Language:

English

Submitter:

Lilian Karin Smith-Wirth

Date Deposited:

30 Mar 2016 10:49

Last Modified:

15 Oct 2017 14:52

Publisher DOI:

10.1038/nrclinonc.2015.103

PubMed ID:

26054909

BORIS DOI:

10.7892/boris.77511

URI:

https://boris.unibe.ch/id/eprint/77511

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