O47: IKK-ALPHA AS A POTENTIAL NOVEL TARGET FOR TREATMENT OF COLORECTAL CANCER

Abstract Introduction There is substantial evidence linking NF-κB and cancer-related processes. The aim of this study was to investigate the role IKKα, main catalytic component non-canonical pathway in colorectal cancer (CRC). Method Immunohistochemistry immunofluorescence used examine expression IKKα 1030 patients undergoing resection for stage I-III CRC. To assess inhibition, organoids were prepared from wild type (WT) mouse colon, models CRC (Apc Apc.KRAS.pT53.TGFbR2 (AKPT)) patient derived human organoids. These treated with an inhibitor, SU1433 organoid size cell viability assessed. Result High cytoplasmic associated increasing T (p=0.012), poor tumour differentiation (p=0.010), necrosis (p=0.013) low proliferation status (p=0.013). punctate reduced CSS (HR1.20 95%CI 1.02-1.42, p<0.001). Immunofluorescence showed co-located a Golgi-related structure. did not significantly impact on WT (C57/B16) up concentration 1uM, however dose-dependent manner both Apc AKPT models. A similar reduction observed Conclusion Punctate specific survival patients. relationship between Golgi requires further investigation. Inhibition SU1433, impacted viability. results suggest that following investigation could be employed as novel therapeutic target Take-home message up-regulated surgery CRC, outcome inhibition has presented itself target. raised interesting questions regarding molecular behaviour warrants