A promising new approach to treating colorectal cancer by disarming the the gene that drives self-renewal in stem cells that are the root cause of disease, resistance to treatment and relapse was discovered by scientists and surgeons at Princess Margaret Cancer Centre. Colorectal cancer is the third leading cause of cancer-related death in the Western world.
"This is the first step toward clinically applying the principles of cancer stem cell biology to control cancer growth and advance the development of durable cures," says principal investigator Dr. John Dick about the findings published online today in Nature Medicine.
He talks about the research in this video - click the link to watch: https://www.youtube.com/watch?v=QK7JquljkBc.
In pre-clinical experiments, the research team replicated human colon cancer in mice to determine if specifically targeting the stem cells was clinically relevant. First, the researchers identified that the gene BMI-1, already implicated in maintaining stem cells in other cancers, is the pivotal regulator of colon cancer stem cells and drives the cycle of self-renewal, proliferation and cell survival. Next, the team used an existing small-molecule inhibitor to successfully block BMI-1, thus demonstrating the clinical relevance of this approach.
Lead author Dr. Antonija Kreso writes: "Inhibiting a recognized regulator of self-renewal is an effective approach to control tumor growth, providing strong evidence for the clinical relevance of self-renewal as a biological process for therapeutic targeting."
Dr. Dick explains: "When we blocked the BMI-1 pathway, the stem cells were unable to self-renew, which resulted in long-term and irreversible impairment of tumour growth. In other words, the cancer was permanently shut down."
Surgeon-scientist Dr. Catherine O'Brien, senior co-author of the study says: "The clinical potential of this research is exciting because it maps a viable way to develop targeted treatment for colon cancer patients. It is already known that about 65% have the BMI-1 biomarker. With the target identified, and a proven way to tackle it, this knowledge could readily translate into first-in-human trials to provide more personalized cancer medicine."