Grant: Operating Grant

Colorectal cancer represents the second leading cause of cancer-related deaths in North America. Despite adequate surgical removal of the primary tumor, relapse of the disease occurs within 5 years in nearly half of the patients, who will eventually die principally due to metastatic spread of the disease. Colorectal cancer represents a progressive disorder arising through the accumulation of multiple heterogeneous genetic and molecular changes that may never be fully identifiable for each colorectal tumor. Hence, one of the challenges in the development of new therapies relies on the identification of targets that regulate biological processes required for the initiation and/or malignant progression of colorectal cancer, i.e.: cell division, survival, invasion, and motility, as well as the formation of new blood vessels, a process termed angiogenesis. These are biological processes under the control of a family of growth factor cell surface receptors with tyrosine kinase activity, which are frequently deregulated in colorectal malignancies, such as the hepatocyte growth factor receptor, also known as the Met receptor. In this project, we will use molecular and cellular approaches, both in vitro and in vivo, to define in the context of the Met RTK, the functional significance of RTK signaling proteins in the initiation and malignant progression of colorectal cancer. These studies will determine which signaling proteins engaged by RTKs represent valid targets for the eventual development of new therapeutic strategies to reduce the growth of primary colorectal tumors and/or the incidence of metastases. Thus, it may have significant impact on future treatments for patients afflicted by this dreadful disease that is colorectal cancer.