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The review discusses drug combinations, including pairing first-line therapy with immunotherapy, and drug repurposing, summarizing current and emerging pharmacological approaches and their preclinical and clinical evidence to improve 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| --- | --- | --- |\n\nSubmit a Manuscript: [https://www.f6publishing.com](https://www.f6publishing.com) World J Gastroenterol 2023 May 7; 29(17): 2571-2599  \nDOI: 10.3748/wjg.v29.i17.2571 ISSN 1007-9327 (print) ISSN 2219-2840 (online)  \nREVIEW  \nCurrent and novel approaches in the pharmacological treatment of hepatocellular carcinoma  \nFernanda Villarruel-Melquiades, María Eugenia Mendoza-Garrido, Claudia M García-Cuellar, Yesennia Sánchez-Pérez, Julio Isael Pérez-Carreón, Javier Camacho  \nSpecialty type: Gastroenterology and hepatology  \nProvenance and peer review:  \nInvited article; Externally peer reviewed.  \nPeer-review model: Single blind  \nPeer-review report’s scientific quality classification  \nGrade A (Excellent): 0  \nGrade B (Very good): B, B  \nGrade C (Good): C  \nGrade D (Fair): 0  \nGrade E (Poor): 0  \nP-Reviewer: Bao YZ, China; Han J, China; Wang C, China  \nReceived: December 27, 2022  \nPeer-review started: December 27, 2022  \nFirst decision: January 11, 2023  \nRevised: January 19, 2023  \nAccepted: April 11, 2023  \nArticle in press: April 11, 2023  \nPublished online: May 7, 2023  \nFernanda Villarruel-Melquiades, Javier Camacho, Departamento de Farmacología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), Mexico City 07360, Mexico  \nMaría Eugenia Mendoza-Garrido, Departamento de Fisiología, Biofísica y Neurociencias, Centrode Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAVIPN), Mexico City 07360, Mexico  \nClaudia M García-Cuellar, Yesennia Sánchez-Pérez, Subdirección de Investigación Básica, Instituto Nacional de Cancerología (INCan), Mexico City 14080, Mexico  \nJulio Isael Pérez-Carreón, Instituto Nacional de Medicina Genómica, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City 14610, Mexico  \nCorresponding author: Javier Camacho, BSc, MSc, PhD, Research Scientist, Departamento de Farmacología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), Avenida Instituto Politécnico Nacional 2508, Mexico City 07360, [Mexico.](Mexico. fcamacho@cinvestav.mx)[ fcamacho@cinvestav.mx](Mexico. fcamacho@cinvestav.mx)  \nAbstract  \nHepatocellular carcinoma (HCC) is one of the most lethal malignant tumours worldwide. The mortality-to-incidence ratio is up to 91.6% in many countries, representing the third leading cause of cancer-related deaths. Systemic drugs, including the multikinase inhibitors sorafenib and lenvatinib, are first-line drugs used in HCC treatment. Unfortunately, these therapies are ineffective in most cases due to late diagnosis and the development of tumour resistance. Thus, novel pharmacological alternatives are urgently needed. For instance, immune checkpoint inhibitors have provided new approaches targeting cells of the immune system. Furthermore, monoclonal antibodies against programmed cell death-1 have shown benefits in HCC patients. In addition, drug combinations, including first-line treatment and immunotherapy, as well as drug repurposing, are promising novel therapeutic alternatives. Here, we review the current and novel pharmacological approaches to fight HCC. Preclinical studies, as well as approved and ongoing clinical trials for liver cancer treatment, are discussed. The pharmacological opportunities analysed here should lead to significant improvement in HCC therapy.  \n WJG  [https://www.wjgnet.com](https://www.wjgnet.com) 2571 May 7, 2023  Volume 29  Issue 17   \nVillarruel-Melquiades F et al. Novel pharmacological approaches in HCC  \nKey Words: Liver cancer; Systemic therapy; Immunotherapy; Drug repurposing; Drug combinations; Hepatocellular carcinoma  \n©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.  \nCore Tip: Hepatocellular carcinoma (HCC) is one of the most lethal malignant tumours worldwide. Unfortunately, most HCC cases are diagnosed at an advanced sta","cbCaieF8ikoCV2Hv","https://ap.wps.com/l/cbCaieF8ikoCV2Hv","pdf",2287977,"English","# Review: Current and novel pharmacological approaches\n## Clinical context and limitations of current systemic therapy\n## Emerging immune-based strategies and targeted monoclonal antibodies\n## Drug combinations and drug repurposing\n## Preclinical evidence and ongoing/approved clinical trials","[{\"question\":\"Why do current first-line drugs for hepatocellular carcinoma often fail?\",\"answer\":\"They are frequently ineffective because HCC is diagnosed late and tumors develop resistance, limiting long-term treatment success.\"},{\"question\":\"What immune-based therapies are highlighted as new approaches for HCC?\",\"answer\":\"Immune checkpoint inhibitors are described as targeting immune-system cells, and monoclonal antibodies against programmed cell death-1 have shown benefits in HCC patients.\"},{\"question\":\"Which novel pharmacological strategies besides immunotherapy are discussed?\",\"answer\":\"The review covers drug combinations, including pairing first-line treatment with immunotherapy, and drug repurposing as promising therapeutic alternatives.\"}]","Current and novel approaches in the pharmacological treatment of hepatocellular carcinoma | PDF",1790250287,76]