About Colorectal Cancer
Colorectal cancer (CRC) represents a major public health problem.
In Denmark approximately 4.000 new cases are diagnosed every year.
At the primary diagnosis 80% of the patients will undergo resection with curative intent, while 20% will only be offered palliative resection due to disseminated disease. However, among the “curatively” resected patients approx. 40-45% will develop recurrent disease within the next five years, resulting in an overall long-term survival of approximately 50%.
Three of the largest challenges in the management of CRC today are the ability to:
detect CRC at earlier stages
distinguish between highly aggressive and latent tumors
predict response to oncological therapy
Early detection will improve survival
At the time of first diagnosis half of the patients will have stage I or II disease, and the other half of the patients will have disseminated disease – stage III or IV.
It is expected that overall survival could be substantially improved if more patients were detected at an earlier stage. However, no current method (biomarker) efficiently enables early detection of CRC in asymptomatic patients.
Different risk of recurrence
Of the “curatively” resected stage II and III cancer patients approximately ~20% and ~50% will experience later recurrence of disease. As a consequence stage II and III patients are offered adjuvant chemotherapy. Unfortunately, the routine prognostic indicators available today cannot distinguish clearly between the patients with high and low recurrence risk. The result is that a significant fraction of the patients are over-treated with chemotherapy regimens that they do not need.
Response to treatment
The major treatment modality for stage IV patients (with distant metastases) is chemotherapy.
Here another problem exists, namely that a large percentage of patients receiving therapy do not obtain an objective remission while they most often experience substantial side effects.
Today oncologists have a wide range of combinatorial regimens available e.g. 5FU/oxaliplatin (FOLFOX, XELOX). Unfortunately, it is currently not possible to predict which combination will be effective for a given patient.
Therefore, one way to improve current oncological management of stage IV patients is to develop predictive biomarkers that can help guiding the oncologist in choosing the most optimal regiment as 1. line treatment. Such an approach should not only result in increased patient survival but also in increased patient quality of life. In addition, the society will save significant economical resources that today are being used on ineffective treatments.
Aims of Research
The approach is translational, integrating clinical and basic studies to identify and develop new molecular markers for CRC to enable early detection and to increase the accuracy of diagnosis, prognosis, and prediction of treatment response.
Current Research Activities
- EU FP7 SYSCOL: ”Systems Biology of Colorectal Cancer”
The aim is to develop a quantitative model of colorectal tumor formation and to apply this for identification of high-risk individuals, for classification of the disease, and for identification of novel treatment targets. See syscol-project.eu.
- Identification and validation of diagnostic biomarkers in plasma
- Identification and validation of molecular biomarkers for predicting response to oncological therapy
- Usage of cancer-specific genomic rearrangements as markers for monitoring disease recurrence and response to therapy
- Cancer-specific 3’UTR switching in colorectal cancer – effect, mechanism, and potential clinical implications
- Identification and validation of diagnostic and prognostic non-coding RNAs in colorectal cancer
SYSCOL - EU FP7 project "Systems Biology of Colorectal Cancer" (2011-2015)
The Colorectal Cancer Tissue Bank
The Colorectal Cancer Tissue Bank is located at the CMCC and is maintained in a collaborative effort by the Colorectal Cancer Group and the
- Department of Surgery, Herning Regional Hospital
- Department of Surgery, Horsens Regional Hospital
- Department of Surgery P, Aarhus University Hospital
- Department of Surgical Gastroenterology L, Aarhus University Hospital
The bank was established in 1999 in order to facilitate the translation of laboratory research into clinical practise.
At the Surgical Departments dedicated nurses and technicians are responsible for the collection of blood, normal colon mucosa, adenoma, adenocarcinoma, and metastatic liver tissues. All patients included have received oral and written information about the tissue bank and have given written consent.
Currently the bank holds biologically and clinically well-defined tissue, carefully isolated RNA, DNA and protein extracts, and associated clinical and pathological data from more than 2000 patients. Roughly 350 new patients are added to the bank each year.
For specific subsets of patient’s tissue microarrays (TMAs) containing formalin fixed and paraffin embedded tumor tissues have been created. Available is for example a TMA with tumor tissue from 300 consecutive collected stage II cancer patients with a minimum of 3 years of follow-up (incl. disease free and overall survival).
The tissue bank has been approved by the Central Denmark Region Committee on Biomedical Research Ethics and the Danish Data Protection Agency.