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Fortunately, advances in systemic treatment options are finally arriving for HCC patients. After a decade of sorafenib as a standard therapy for advanced HCC, several tyrosine kinase inhibitors (TKIs), antiangiogenic antibodies, and immune checkpoint inhibitors have reached the clinic. Although infections by hepatitis B virus and hepatitis C virus remain principal factors for HCC development, the rise of non- alcoholic steatohepatitis from diabetes mellitus or metabolic syndrome is impeding HCC decline. Knowledge of specific molecular mechanisms, based on the etiology and the HCC microenvironment that influence tumor growth and immune control, will be crucial for physician decision-making among a variety of drugs to prescribe. In addition, markers of treatment efficacy are needed to speed the movement of patients towards other potentially effective treatments. Consequently, research to provide scientific data for the evidence-based management of liver cancer is guaranteed in the coming years and discussed here.<\/jats:p>","DOI":"10.3390\/cancers14030621","type":"journal-article","created":{"date-parts":[[2022,1,26]],"date-time":"2022-01-26T11:02:53Z","timestamp":1643194973000},"page":"621","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":70,"title":["Hepatocellular Carcinoma: Molecular Pathogenesis and Therapeutic Advances"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5860-362X","authenticated-orcid":false,"given":"Blanca","family":"Cucarull","sequence":"first","affiliation":[{"name":"Department of Cell Death and Proliferation, IIBB-CSIC, IDIBAPS, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1133-321X","authenticated-orcid":false,"given":"Anna","family":"Tutusaus","sequence":"additional","affiliation":[{"name":"Department of Cell Death and Proliferation, IIBB-CSIC, IDIBAPS, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Rider","sequence":"additional","affiliation":[{"name":"Department of Cell Death and Proliferation, IIBB-CSIC, IDIBAPS, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tania","family":"Hern\u00e1ez-Alsina","sequence":"additional","affiliation":[{"name":"Digestive Unit, Hospital San Pedro, Rioja Salud, 26006 Logro\u00f1o, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Cu\u00f1o","sequence":"additional","affiliation":[{"name":"Department of Cell Death and Proliferation, IIBB-CSIC, IDIBAPS, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1547-1190","authenticated-orcid":false,"given":"Pablo","family":"Garc\u00eda de Frutos","sequence":"additional","affiliation":[{"name":"Department of Cell Death and Proliferation, IIBB-CSIC, IDIBAPS, 08036 Barcelona, Spain"},{"name":"Unidad Asociada (IMIM), IIBB-CSIC, CIBERCV, IDIBAPS, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5236-1834","authenticated-orcid":false,"given":"Anna","family":"Colell","sequence":"additional","affiliation":[{"name":"Department of Cell Death and Proliferation, IIBB-CSIC, IDIBAPS, 08036 Barcelona, Spain"},{"name":"Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6116-3247","authenticated-orcid":false,"given":"Montserrat","family":"Mar\u00ed","sequence":"additional","affiliation":[{"name":"Department of Cell Death and Proliferation, IIBB-CSIC, IDIBAPS, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8702-2269","authenticated-orcid":false,"given":"Albert","family":"Morales","sequence":"additional","affiliation":[{"name":"Department of Cell Death and Proliferation, IIBB-CSIC, IDIBAPS, 08036 Barcelona, Spain"},{"name":"Barcelona Clinic Liver Cancer Group, Liver Unit, Hospital Cl\u00ednic of Barcelona, University of Barcelona, CIBEREHD, IDIBAPS, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,26]]},"reference":[{"key":"ref_1","unstructured":"Ferlay, J., Ervik, M., Lam, F., Colombet, M., Mery, L., Pi\u00f1eros, M., Znaor, A., Soerjomataram, I., and Bray, F. 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