title: Rethinking future development of molecular therapies in hepatocellular carcinoma: a bottom-up approach.
abstract: The high failure rate of phase 3 trials in oncology is forcing the scientific community to rethink drug development strategies and optimize trial design. The current paradigm of systemic therapies is progressively favoring molecular-based patient selection. In hepatocellular carcinoma, four out of the five phase 3 trials that tested molecular therapies in the last 5 years have been negative. None of them included enriched populations using predicted biomarkers of response. Hence, there is an increasing need to provide new targets and refine selection criteria in HCC clinical trials using molecular readouts of tumor biology.
authors.affiliation: HCC Translational Research Laboratory, Barcelona-Clínic Liver Cancer Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Liver Unit, Hospital Clínic, Barcelona, Catalonia, Spain. augusto.villanueva@ciberehd.org
authors.forename: Augusto
authors.initials: A
authors.lastname: Villanueva
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D017326:Clinical Trials, Phase III as Topic; D055808:Drug Discovery / Q000639:trends; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy*; D058990:Molecular Targeted Therapy / Q000639:trends*; D009536:Niacinamide / Q000031:analogs & derivatives / Q000627:therapeutic use; D018579:Patient Selection; D010671:Phenylurea Compounds / Q000627:therapeutic use; D000077157:Sorafenib; D017211:Treatment Failure
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib
keywords: Clinical trials; Liver cancer; Personalized medicine; Sorafenib