Based on the emerging paradigm in oncology, effective treatments will need to target cancer stem cells, which are the cells that become overpopulated during tumorigenesis and drive tumor growth. To understand how stem cell overpopulation drives tumor growth, Dr. Boman’s lab has been studying the effect of the main mutation (i.e. APC) that drives the development of colorectal cancer. APC mutations are the most frequent (>85%) genetic alteration occurring in colorectal cancers. Dr. Boman’s lab found that APC mutations cause progressive expansion of the SC population during development of colorectal cancer in humans. This finding led to the publication that stem cell overproduction results from increased symmetric stem cell division.
Dr. Boman’s lab recently discovered that ALDH is a marker for colonic stem cells, and allows the tracking of stem cell overpopulation due to APC mutation during colon cancer development. This recent discovery raised the question: What are the underlying mechanisms that lead to stem cell overpopulation? To seek an answer, Dr. Boman’s lab is currently investigating which ALDH isoforms are critical to ALDH activity, whether specific pathways, such as neuroendocrine or retinoid, are involved in maturation and death of cancer stem cells, and what kinetic mechanisms drive colon cancer growth and development. Based on their research findings, the lab’s scientific team postulates that targeting the cellular mechanisms affected by APC mutation that cause cancer stem cell overpopulation and drive colon tumor growth offers a new and more effective approach toward treatment of colorectal cancer.
Overall, the research findings by this team of scientists at the Cawley Center for Translational Cancer Research provide new concepts on how discoveries from basic cancer research might be translated into the clinical setting with the development of new therapies for patients with advanced stages of colorectal cancer.