HEPTROMIC

Genomic predictors and oncogenic drivers in hepatocellular carcinoma

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 Obiettivo del progetto (Objective)

'Hepatocellular carcinoma (HCC) accounts for more than 90% of liver cancers, and is a major health problem. Its incidence is growing and with more than 700,000 annual cases worldwide -50,000 in Europe-, it is the 3rd cause of cancer-related mortality. Most patients are diagnosed at advanced stages with dismal survival rates lower than 1 year, even after sorafenib, the sole systemic therapy available. The main goal of the HEPTROMIC project is to produce breakthrough knowledge in two critical aspects of HCC research: prognostic prediction and identification of oncogenic drivers susceptible for intervention, leading towards more personalized treatment algorithms. The HEPTROMIC Consortium proposes a 3-year translational research study bringing together an outstanding team of researchers with clinical and genomic expertise along with cutting-edge technology. Eight partners -six academic and two SMEs- will address the following objectives by applying high-end transcriptome, methylome and deep sequencing technology in a large set of 1,140 human samples: Objective 1) Genomic characterization of poor prognosis subclass of hepatocellular carcinoma. Objective 2) Identification of driver oncogenic events as potential treatment targets. Findings obtained will be confirmed in sophisticated experimental models that closely mimics human liver cancer. Objective 3) Design of prognostic devices for clinical translation. This transfer of knowledge will be led by SMEs with entrepreneurial management skills with experience in creating new products increasing European competitiveness and boosting the innovative capacity of industries. Overall, the Consortium foresees impacts on improved patient survival by refining prognosis and decision-making, identifying targets amenable for selective therapies and by improving the allocation of resources. In summary, HEPTROMIC will strength links between the academic and industry spheres, ultimately contributing to reduce liver cancer mortality.'

Introduzione (Teaser)

Exploitation of recent major technological advances in genomic characterisation could help identify biomarkers for cancer prognosis as well as potential therapeutic targets.

Descrizione progetto (Article)

Hepatocellular carcinoma (HCC) is the most prevalent form of liver cancer, and is the third cause of cancer-related deaths worldwide. The incidence of the disease is increasing, with more than 700 000 new cases per year worldwide. Only one third of newly diagnosed patients are eligible for curative treatments and the overall poor survival rates necessitate the urgent development of novel regimens.

Understanding the molecular changes that determine liver cancer development and progression is expected to make key contributions to the design of novel targeted therapies. A classic example in this field is the development of sorafenib, a tyrosine kinase inhibitor that acts on hepatocellular and renal cell carcinoma.

With this in mind, the EU-funded 'Genomic predictors and oncogenic drivers in hepatocellular carcinoma' (Heptromic) initiative aims to address two important aspects of HCC biology. The project will make step change advances in the field by defining biomarkers for identification of HCC patients with poor prognosis and novel genetic or epigenetic drivers that are critical for a more personalised therapeutic approach.

A number of cancer and normal cell samples have been subjected to gene expression, methylation and kinome analysis. These data have enabled scientists to classify tumours based on epigenetic markers and non-coding RNAs.

Partners have identified specific molecular signatures to be associated with early and overall HCC recurrence. In terms of epigenetic regulation of gene expression, over 2,100 coding genes, 184 non-coding RNAs and 34 microRNAs have been defined as differentially methylated between HCC and normal tissue. This new knowledge is the basis for developing significantly enhanced predictive capacity in HCC prognosis.

A combination of clinical and genomic data will act as a prognostic platform to define a patient's risk of tumour recurrence or death with increased precision. Ongoing work towards the identification of oncogenes capable of driving cancer formation will lead to the development of novel therapeutic targets for HCC.

Generation of products and services incorporating the project discoveries are expected to improve prognosis of HCC. Furthermore, refinement of the risk stratification of patients according to solid biomarkers will lead to a direct improvement in treatment outcome and resource allocation.