Grant: CIHR Fellowship

Despite decades of research and development of diagnostic technology, cancer is still often diagnosed based on relatively large abnormalities in the tissue - growths, lumps, or bumps visible to the naked eye. The size of the smallest detectable tumor is still approximately a billion cells. Furthermore, it is often only possible to detect cancer cells that have spread from the initial tumor site to distant organs at late stages, when the cancer has progressed past the point of being curable. Thus, being able to identify cancer cells at very early stages and low numbers could enable identification of molecules to mark cancerous and pre-cancerous cells, and lead to development of therapies to kill cancer cells before the cancer spreads. One potential way to identify cancer cells at early stages is by discovering novel mechanisms cancer cells use to promote their own growth and survival. Cell competition is a process by which faster growing ("winner") cells kill the slower growing ("loser") cells around them, in order to enable their own growth. Although cell competition is known to be important for animal development and for maintaining tissue health, it has not been extensively studied in cancer in animals. I will use a zebrafish model of melanoma to investigate if cancer cells use cell competition to promote their own growth by killing the cells around them. I will transplant melanoma cells into transparent fish and use cutting-edge live, whole-animal microscopy to investigate if tumors cause the death of the surrounding normal cells. In parallel, I will induce cell competition in tumors by upregulating the cancer-promoting gene Myc, and perform a drug screen to identify molecules that inhibit competition and tumor growth, to provide insight into signaling pathways that could be driving cell competition in cancer. These studies will detail molecules that promote cancer progression, and describe potential targets for development of drugs to block cancer spreading.