17.05.17

Researchers from Aarhus University Hospital and Aarhus University have discovered that several sub-types of colorectal cancer exist and that some tumors within each sub-type are more aggressive than others. This new knowledge may make it possible to optimise treatment and improve survival.

Colorectal cancer is one of the most frequent and fatal cancers in the world. Although 2/3 of patients receive curative treatment, approximately 1/3 experience relapse after treatment.

To reduce this number, it is important that patients with aggressive tumours and thus an increased risk of disease relapse are identified and offered extra treatment to increase their survival.

New results from a large study conducted by researchers at Department of Molecular Medicine at Aarhus University Hospital point to a new way of identifying these aggressive tumours.

Tumours are very different

In a close collaboration with surgeons at Aarhus University Hospital and Regional Hospital West Jutland, researchers have found that colorectal tumours, despite many similarities, are very different at the molecular level.

Colorectal cancer should therefore no longer be regarded as one disease but rather as a common denominator for a number of different colorectal cancer sub-types. With this new insight, researchers have developed a method to identify aggressive tumors by adapting their analyses to each sub-type.

- In colorectal cancer, tumours are generally divided into a number of molecular sub-types, which not only encompass different cancer cell types but also vary dramatically in their content of surrounding normal cells such as immune cells, says head of the research project, Claus Lindbjerg Andersen, Department of Molecular Medicine at Aarhus University Hospital.

- The content of the normal cells and their impact on the cancer cells have a huge influence on the ability of cancer cells to develop metastases and the patients' course of disease.

- We therefore have to adapt the analyses to the tumour sub-type to identify patients with aggressive disease. That is the principle of our method.

Improved targeted treatment

The researchers analysed more than 1000 colorectal tumours and identified five molecular sub-types with distinct differences in biology and course of disease. This new distinction allowed identification of a number of biological mechanisms contributing to the aggressiveness of the disease.

The researchers demonstrated that different molecular analyses were necessary to identify aggressive tumours in each sub-type. These analyses are now integrated in one model, which can improve prognostics of aggressive disease compared to current methods.

- At the moment, it is difficult to predict aggressiveness of colorectal cancer based on tissue analyses alone, says Jesper Bramsen, Associate professor at Department of Molecular Medicine, who is the key researcher in the project.

- It will be a big step forward if the molecular predictions could help tailoring follow-up treatment to the individual patient. Patients with aggressive disease could be treated intensively while other patients could receive less intensive treatment with fewer side effects. With this project we have initiated the development of such molecular methods.

Clinical testing is next

Researchers also believe that the method can be adapted to predict treatment efficiency of chemotherapy and immune therapy, which is the next important step to optimise follow-up treatment in patients with colorectal cancer.

- We work intensely on further developing the method and test it in practice as a new molecular tool to plan the treatment pathway for patients with colorectal cancer, says professor Claus Lindbjerg Andersen.

Link to original article:

Results are published in the internationally acknowledged journal Cell Reportswith the title:

Molecular Subtype-specific Biomarkers Improve Prediction of Prognosis in Colorectal Cancer

Jesper Bertram Bramsen,Mads Heilskov Rasmussen, Halit Ongen, Trine Block Mattesen, Mai-Britt Worm Ørntoft, Sigrid Salling Árnadóttir, Juan Sandoval, Teresa Laguna, Søren Vang, Bodil Øster, Philippe Lamy, Mogens Rørbæk Madsen, Søren Laurberg, Manel Esteller, Emmanouil Dermitzakis, Torben Falck Ørntoft, og Claus Lindbjerg Andersen.

http://www.cell.com/cell-reports/fulltext/S2211-1247(17)30539-9  

Further information:

Claus Lindbjerg Andersen, Professor, Department of Molecular Medicine, Aarhus University Hospital, Tel.: + 45 78 45 53 19.