Targeting therapy-resistant stem cells in a model for genetically predisposed colon cancer
Study Rationale: Negative or positive regulation in the expression of tumour suppressor genes or oncogenes impact progression of colon cancer. Germ line mutation in the tumour suppressor adenomatous polyposis coli (APC) gene represents a primary genetic defect leading to familial adenomatous polyposis (FAP) syndrome predisposing colon carcinogenesis. Therapeutic modulation of these genetic events is modestly effective. Targeted therapy with Cyclo-oxygenase (COX) inhibitors has exhibited preclinical and clinical efficacy. Long-term therapy exhibits systemic toxicity, acquired tumour resistance and emergence of therapy resistant cancer stem cells impacting progression of cancer. Non-toxic natural products may not exhibit drug resistance and therefore, may represent testable alternatives for therapy resistant colon cancer.