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      Molecular pathogenesis and systemic therapies for hepatocellular carcinoma

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          Abstract

          Hepatocellular carcinoma (HCC) remains one of the most prevalent and deadliest cancers. The poor outcome associated with HCC is dramatically changing due to the advent of effective systemic therapies. Here we discuss the molecular pathogenesis of HCC, molecular classes and determinants of heterogeneity. In addition, effective single-agent and combination systemic therapies involving immunotherapies as standard of care are analyzed. Finally, we propose a flowchart of sequential therapies, explore mechanisms of resistance and address the need of predictive biomarkers.

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          EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma

          Valérie Vilgrain, Peter Galle, Alejandro Forner … (2018)
          Article 0 comments Cited 2571 times – based on 0 reviews     Review now
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            Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma

            Richard S Finn, Shukui Qin, Masafumi Ikeda … (2020)
            The combination of atezolizumab and bevacizumab showed encouraging antitumor activity and safety in a phase 1b trial involving patients with unresectable hepatocellular carcinoma.
            Article 0 comments Cited 2422 times – based on 0 reviews     Review now
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              Sorafenib in advanced hepatocellular carcinoma.

              Josep Llovet, Sergio Ricci, Vincenzo Mazzaferro … (2008)
              No effective systemic therapy exists for patients with advanced hepatocellular carcinoma. A preliminary study suggested that sorafenib, an oral multikinase inhibitor of the vascular endothelial growth factor receptor, the platelet-derived growth factor receptor, and Raf may be effective in hepatocellular carcinoma. In this multicenter, phase 3, double-blind, placebo-controlled trial, we randomly assigned 602 patients with advanced hepatocellular carcinoma who had not received previous systemic treatment to receive either sorafenib (at a dose of 400 mg twice daily) or placebo. Primary outcomes were overall survival and the time to symptomatic progression. Secondary outcomes included the time to radiologic progression and safety. At the second planned interim analysis, 321 deaths had occurred, and the study was stopped. Median overall survival was 10.7 months in the sorafenib group and 7.9 months in the placebo group (hazard ratio in the sorafenib group, 0.69; 95% confidence interval, 0.55 to 0.87; P<0.001). There was no significant difference between the two groups in the median time to symptomatic progression (4.1 months vs. 4.9 months, respectively, P=0.77). The median time to radiologic progression was 5.5 months in the sorafenib group and 2.8 months in the placebo group (P<0.001). Seven patients in the sorafenib group (2%) and two patients in the placebo group (1%) had a partial response; no patients had a complete response. Diarrhea, weight loss, hand-foot skin reaction, and hypophosphatemia were more frequent in the sorafenib group. In patients with advanced hepatocellular carcinoma, median survival and the time to radiologic progression were nearly 3 months longer for patients treated with sorafenib than for those given placebo. (ClinicalTrials.gov number, NCT00105443.) 2008 Massachusetts Medical Society
              Article 0 comments Cited 2083 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-journal-id): 101761119
                Journal ID (pubmed-jr-id): 49159
                Journal ID (nlm-ta): Nat Cancer
                Journal ID (iso-abbrev): Nat Cancer
                Title: Nature cancer
                ISSN (Electronic): 2662-1347
                Publication date Nihms-submitted: 27 February 2022
                Publication date (Print): April 2022
                Publication date (Electronic): 28 April 2022
                Publication date PMC-release: 28 October 2022
                Volume: 3
                Issue: 4
                Pages: 386-401
                Affiliations
                [1 ]Liver Cancer Translational Research Laboratory, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, Universitat de Barcelona, Barcelona, Catalonia, Spain.
                [2 ]Mount Sinai Liver Cancer Program (Divisions of Liver Diseases, Department of Hematology/Oncology, Department of Medicine), Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, USA.
                [3 ]Institució Catalana de Recerca i Estudis Avançats, Barcelona, Catalonia, Spain.
                [4 ]Helen Diller Cancer Center, University of California San Francisco, San Francisco, CA, USA.
                [5 ]Keck School of Medicine, USC Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
                [6 ]Newcastle University Translational and Clinical Research Institute and Newcastle University Centre for Cancer, Medical School, Framlington Place, Newcastle Upon Tyne, NE2 4HH, UK.
                [7 ]Hepatopancreatobiliary Multidisciplinary Team, Newcastle upon Tyne NHS Foundation Trust, Freeman Hospital, Newcastle upon Tyne, UK.
                [8 ]Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
                [9 ]Liver Cancer Program, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
                [10 ]Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.
                Author notes
                [* ] Corresponding author: Josep M. Llovet, MD, PhD, FAASLD. Mount Sinai Liver Cancer Program, Division of Liver Diseases, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, Madison Ave 1425. 11F-70. Box 1123, New York, NY10029. USA. josep.llovet@ 123456mountsinai.org
                Author information
                http://orcid.org/0000-0003-0547-2667
                http://orcid.org/0000-0002-0288-6314
                http://orcid.org/0000-0002-1984-2430
                http://orcid.org/0000-0002-9053-3841
                http://orcid.org/0000-0003-0359-9795
                http://orcid.org/0000-0001-9735-606X
                http://orcid.org/0000-0003-3151-009X
                http://orcid.org/0000-0003-3585-3727
                Article
                Manuscript ID: NIHMS1784308
                DOI: 10.1038/s43018-022-00357-2
                PMC ID: 9060366
                PubMed ID: 35484418
                SO-VID: 624aa260-e493-470e-b269-026ae1a5640b
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