Page 71 - ebook HCC

68 PROGRAMME AND ABSTRACTS GENEVA, SWITZERLAND EASL HCC SUMMIT 69
FEBRUARY 13 - 16, 2014

PHOSPHOPROTEOME IN HEPATOCELLULAR NOTES
CARCINOMA

Augusto Villanueva 1
1 King’s College London, London, United Kingdom

Corresponding author’s e-mail: augusto.villanueva@kcl.ac.uk

Current mainstream trends in systemic therapy for solid tumors mostly rely in the selective
blockade of tyrosine kinases. The main biochemical mechanism of kinase activation is
constitutive phosphorylation, generally due to an activating mutation. Ideally, identification
of the dominant aberrant activated kinase would allow tailoring treatment on an individual
basis. This has proved effective in different solid tumours such as in patients with lung
BASIC SPEAKERS ABSTRACTS melanoma and vemurafenib. In hepatocellular carcinoma (HCC), solid preclinical and BASIC SPEAKERS ABSTRACTS
cancer, ALK rearrangements and response to crizotinib, or in those with BRAF mutated
clinical evidence indicates that blocking tyrosine kinases provides enough antitumor
effect to increase patient’s survival. However, successful results of sorafenib haven’t been
reproduced with other tyrosine kinase inhibitors, either due to futility or toxicity. Indeed,
it is unclear which is the precise mechanism by which sorafenib induce its antitumoral
effects. Extensive mapping of the de-regulated kinases in HCC could provide additional
clues of potential new therapeutic pathways, or suggest mechanisms behind resistance
to sorafenib.