Marco Gerling

Colon and rectal cancer is our third most common form of cancer and about a third are diagnosed with daughter tumors in the liver - liver metastases. Despite advances in surgery and oncology, spread to the liver means a significantly worse prognosis with shorter survival. Cancer cells in the liver grow by replacing healthy liver cells and then use the liver's own vascular system. The cancer cells' ability to replace healthy tissue can be assessed under the microscope, by studying the metastases invasion front. We and others have shown that the better the cancer cells are at replacing healthy liver cells, the worse the prognosis for the patient. Our research group studies the basic mechanisms that control how cancer cells replace healthy liver cells. We use mouse models in combination with a new method to map the gene expression of individual cells. With these experiments, we have identified a new type of liver cell that communicates directly with the tumor cells. These results have allowed us to now for the first time map the signaling pathways that control tumor invasion in metastases. In this project, we want to apply this new knowledge about how the metastases grow to improve the risk assessment and ultimately the treatment for patients with liver metastases from colon and rectal cancer. We will map the significance of the new liver cell we have identified both with animal experiments and by analyzing tissue from our patients. For this, we have collected data on patients who were operated on for liver metastases at Karolinska Hospital and established collaborations with international research groups and now have data from several thousand patients. We hope that the results can lead to clinically useful markers that would improve and individualize the management and choice of treatment for these patients, as well as contribute to new medical treatments that prevent the cancer cells from replacing healthy liver cells.