Pharmacological inhibition of the paracrine, cell proliferative function of caspase-3 for the treatment of colorectal cancer

Our research group has recently demonstrated that when cells undergo caspase-dependent apoptosis, they send out biochemical signals into their local environment that stimulate the proliferation and differentiation of neighbouring cells. In this project we validate these findings by analysing caspase 3 expression in a large cohort of colorectal cancer patients, and identify whether gene expression and promoter methylation may function as an additional prognostic marker. In a parallel study, we will perform key translational preclinical studies to test the concept that caspase-3 inhibition with the FDA-approved caspase-activation inhibitor Minocycline, or with highly selective caspase-3 inhibitors reduce clonogenic survival in colorectal cancer patient spheroid explant cultures after exposure to 5-Fluorouracil/Oxaliplatin in addition to a pre-clinical xenograft mouse model of colon cancer. This research will deliver novel prognostic markers for therapy success in colorectal cancer.

This project is funded by HRB.