Ron Firestein Lab

PROJECT 4: Targeting Wnt/beta-catenin signalling for colon cancer therapy

The Wnt/β-catenin pathway is critical for both intestinal epithelial homeostasis and cancer development. Genetic mutations in Wnt/β-catenin signalling components, such as APC or β-catenin, play key roles in colon cancer initiation and progression. Wnt/β-catenin signalling has been regarded as one of the most important therapeutic targets in colon cancer.

In this project, we utilise novel Wnt reporter assays coupled to CRISPR genetic knockout technology to systematically and comprehensively identify therapeutically relevant targets of this pathway. Through genome-scale screening of Wnt reporters and integrative network analysis, we have characterised a variety of novel regulators of Wnt/β-catenin signalling.

The project will investigate whether genetically and pharmacologically targeting these regulators may specifically block Wnt/β-catenin signalling and colon cancer malignancy. We aim to identify pharmacological inhibitors of Wnt/β-catenin signalling and develop targeted therapies that block colon cancer malignancy and induce its regression. We will also find targeted strategies that induce colon cancer differentiation into non-tumour cells via blocking Wnt-driven colon cancer stemness.