title: New biological perspectives for the improvement of the efficacy of sorafenib in hepatocellular carcinoma.
abstract: Sorafenib, an orally-available kinase inhibitor, is the only medical treatment with a proven efficacy against Hepatocellular Carcinoma (HCC). Although the overall clinical efficacy of sorafenib is modest, recent experimental results have uncovered new potential strategies that may increase its clinical benefits. The potential implication of Receptor Tyrosine Kinases (RTKs), such as the Epidermal Growth Factor Receptor (EGFR), in the development of resistance to sorafenib highlights the importance of the RAF kinase pathway. Various strategies aiming to optimize the control exerted over this pathway by combining sorafenib with other targeted molecules (such as anti-EGFR, anti-MEK) are under investigation. Increasing the cytotoxicity of sorafenib in HCC, either through apoptosis or through new forms of non-apoptotic cell death, such as ferroptosis, may also promote more sustained tumour regression. Finally, the heterogeneity of individual responses to sorafenib is increasingly recognised, even though clinically-applicable biomarkers remain to be identified. Here, we discuss how molecular genetics and complementary approaches such as short term culture of tumour samples could help to personalize the use of sorafenib.
authors.affiliation: EA4666, Université de Picardie Jules Verne, Amiens, France; Service de Biochimie, CHU Amiens, France. Electronic address: Galmiche.Antoine@chu-amiens.fr.
authors.forename: Antoine
authors.initials: A
authors.lastname: Galmiche
authors.affiliation: EA4666, Université de Picardie Jules Verne, Amiens, France; Service d'Oncologie Médicale, CHU Amiens, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Chauffert
authors.affiliation: EA4666, Université de Picardie Jules Verne, Amiens, France; Direction de la Recherche Clinique et de l'Innovation, CHU Amiens, France.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Barbare
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage; D014408:Biomarkers, Tumor / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002986:Clinical Trials as Topic; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives*; D010671:Phenylurea Compounds / Q000008:administration & dosage*; D057285:Precision Medicine / Q000379:methods; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D000077157:Sorafenib
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D009536:Niacinamide; D000077157:Sorafenib
keywords: Cell death; Hepatocellular carcinoma; Resistance; Sorafenib; Treatment personalization