title: Molecularly targeted therapy for advanced hepatocellular carcinoma - a drug development crisis?
abstract: Hepatocellular carcinoma is the fastest growing cause of cancer related death globally. Sorafenib, a multi-targeted kinase inhibitor, is the only drug proven to improve outcomes in patients with advanced disease offering modest survival benefit. Although comprehensive genomic mapping has improved understanding of the genetic aberrations in hepatocellular cancer (HCC), this knowledge has not yet impacted clinical care. The last few years have seen the failure of several first and second line phase III clinical trials of novel molecularly targeted therapies, warranting a change in the way new therapies are investigated in HCC. Potential reasons for these failures include clinical and molecular heterogeneity, trial design and a lack of biomarkers. This review discusses the current crisis in HCC drug development and how we should learn from recent trial failures to develop a more effective personalised treatment paradigm for patients with HCC.
authors.affiliation: Kiruthikah Thillai, Paul Ross, Debashis Sarker, Department of Medical Oncology, Guy's and St Thomas NHS Trust, London SE1 9RT, United Kingdom.
authors.forename: Kiruthikah
authors.initials: K
authors.lastname: Thillai
authors.affiliation: Kiruthikah Thillai, Paul Ross, Debashis Sarker, Department of Medical Oncology, Guy's and St Thomas NHS Trust, London SE1 9RT, United Kingdom.
authors.forename: Paul
authors.initials: P
authors.lastname: Ross
authors.affiliation: Kiruthikah Thillai, Paul Ross, Debashis Sarker, Department of Medical Oncology, Guy's and St Thomas NHS Trust, London SE1 9RT, United Kingdom.
authors.forename: Debashis
authors.initials: D
authors.lastname: Sarker
keywords: Genomics; Hepatocellular carcinoma; Molecular targets; Sorafenib; Tyrosine kinase inhibitors