Background

The pathogenesis of 15% of human cancers has been linked to inflammation. One of the most prevalent inflammation driven cancers is colitis-associated colorectal cancer (CRC). Annually in Ireland - CRC is responsible for 15% of all cancer related deaths with an average of 1445 cases ( Figure 1. ).

Early stages of progression to CRC, particularly distinguishing between inflammation and true dysplasia, is not as straightforward, and there is a large amount of variation between pathologists identification and grading of dysplasia. Patients who have had colitis for >10 years are advised to undergo regular colonoscopy to detect preinvasive neoplastic lesions. High grade inflammation is also regarded as an indication for colectomy.

Technology Overview

Trinity College have identified caspases-4 and -5 as potential targets for limiting intestinal inflammation and, furthermore, identified epithelial-expressed caspases-4 and -5 as novel targets with diagnostic and therapeutic potential for CRC.

Technology Status:

Inflammatory caspase expression has been examined in IBD patients, an examination of adjacent-normal, inflamed and tumour tissue from patients with ulcerative colitis-associated CRC confirmed that stromal expression of caspases-4 and -5 is increased in inflamed and dysplastic tissue, while epithelial expression is restricted to neoplastic tissue.

Applications

There is a serious requirement for an additional early marker of dysplasia in this context, and the role and expression of enzyme proteins involved in inflammation has been examined. The increased expression of enzyme proteins ‘caspase-4’ and ‘caspase-5‘ correlated to inflammation and disease activity in irritable bowel disease and CRC patients. This technology allows improved accuracy of diagnosis, early treatment, reduction in colectomies and improvement in quality of life.

Biomarkers for Colorectal Cancer

Patents

IP Status