Grant: Project Grant

BACKGROUND: Metastasis is the process by which cancer cells from a primary tumor can travel through the blood to other organs and form a second tumor. About one in four patients with colon cancer will experience metastases in the liver. All too often, patients die as a result of liver metastases. We do not yet know enough about how cancer cells form a metastasis in the liver. By looking at liver metastases with a microscope, we have observed that there are two patterns of tumour growth in the liver. We can determine these growth patterns when the metastatic lesion in the liver is removed by a surgeon and have found that one growth pattern is assocoated with a more favourable outcome (desmoplastic metastases) for the patient when compred to the other (replacement metastases). OBJECTIVES: Currently, the more aggressive form of colorectal cancer liver metastasis can only be treated with chemotherapy, with limited success. Our data indicate that the less aggressive (desmoplastic) and more aggressive (replacement) type liver metastases are metabolically different. We have identified several metabolic programs that are specifically engaged in replacement type colorectal cancer liver metastases. The goal of this research project to determine how important the metabolic programs we have identified are to the growth of colorectal cancer liver metastases and to develop therapeutic strategies to target these programs. SIGNIFICANCE: Currently, patients that develop replacement type colorectal cancer liver metastases can only be treated with chemotherapy. Often, patients will initially respond to chemotherapy but will unfortunately become resistant to this treatment and continue to progress. Our data suggests that these types of lesions could be targeted with metabolic therapies to improve outcomes for colorectal cancer with liver-metastatic disease.