Each FGFR comprises three components, an extracellular domain which interacts with the FGF ligand, a transmembrane domain, and an intracellular domain. The human FGF family consists of 22 structurally related molecules that interact with four FGFRs. We attempt to review the importance of the FGF/FGFR pathway and current clinical evidence to date for use of the pathway inhibitors in HCC.įGF/FGFR pathway and its aberrations in cancer Preclinical models suggest that inhibition of the FGFR pathway is a feasible therapeutic strategy and many clinical trials using FGF/FGFR pathway inhibitors have since been conducted or are ongoing in hepatocellular carcinoma. One signaling pathway that is increasingly recognized to play a role in the carcinogenesis of HCC is the fibroblast growth factor (FGF)/fibroblast growth factor receptor (FGFR) pathway, which has roles in oncogenesis, mediating cell proliferation and neo-angiogenesis. With improving technologies, we have been able to learn more about the molecular mechanisms underlying the oncogenesis of HCC, and in recent past have seen breakthroughs with several new drugs being added to our armamentarium both in the front-line and second-line setting, and many more compounds showing great promise on the horizon. The molecular complexity and heterogeneity of HCC likely underlies the reason for failure of multiple phase III trials of targeted agents over the years.

HCC tumours harbour an average of 30-40 mutations, of which 20% may be driver mutations. In unresectable advanced disease, sorafenib used to be the only available systemic therapy option available and prognosis was poor with a one-year survival rate of less than 50%. Most patients have advanced disease on diagnosis. Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death globally.

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