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Defining interactions between the cytokine IL-22 and oncogenic KRAS as a new therapeutic target in colorectal cancer.

Project Aims

Inflammation and immunity are critical modulators of colorectal cancer progression. While anti-tumour immunity is generally associated with a favourable prognosis, inflammation driven by the IL-23/Th17 axis is related to poor outcome in colorectal cancer. The Th17 cytokine IL-22 promotes colorectal cancer progression in animal models of colitis-associated and sporadic cancer, as well as malignant behaviour in human colorectal cancer cell lines.

 This project will test IL-22 signalling as a driver of tumour progression in molecularly defined subsets of colorectal cancer patients. Tissues from diagnostic biopsies and surgical resections will be analysed for association between IL-22 receptor expression and oncogene mutations and their impact on tissue biology. The project will also include experimental medicine studies to test whether blocking the IL-23 pathway can alter tumour biology.