Funding provided by Helse Sør

Project summary:
The incidence of colorectal cancer (CRC) is increasing, and more than 3000 new cases are diagnosed yearly in Norway. CRC develops through an adenoma – carcinoma sequence where distinct molecular alterations are linked to the various stages. At time of diagnosis, CRC patients are categorised into four clinicopathological stages, Dukes’ A to D. More than 90% of the patients in Dukes’ A survive beyond 5 years, whereas most of the patients
in Dukes’ D die within 5 years. Among the intermediate groups, Dukes’ B and C about 60% are alive after 5 years. Chemotherapy is now standard for Dukes’ C after it was shown that the number of 5 year survivors increased from 45% to 60%. However, about half would have been cured with surgery alone, and 35%-40% die regardless of adjuvant therapy. Furthermore, among Dukes’ B some could benefit from more aggressive treatment. Taken
together, this show the need for new informative predictive and prognostic markers to aid in the identification of those who will benefit from more aggressive therapy and those who is best treated with surgery alone.

In order to gain novel insights into the tumour development that may be transferred into such clinical utility we are performing epigenetic and genetic studies on relevant in vitro models as well as patient materials.

We combine the candidate gene and pathway approach with the discovery based investigations using various large scale technologies. Validation of biomarkers will be performed by use of tissue microarrays, and a molecular stratification both for complex datasets and for individual markers will be performed in order to predict disease outcome.