MRC DTP in Precision Medicine

Establishing the role of non-canonical NFκB signalling within the tumour microenvironment of colorectal cancer

Supervisors

Dr Colin Steele, School of Cancer Sciences, University of Glasgow
Dr Kevin Myant, Insititute of Genetics and Cancer, University of Edinburgh
Dr Xiao Fu, School of Cancer Sciences, University of Glasgow
Dr Kathryn Pennel, School of Cancer Sciences, University of Glasgow

Summary

Colorectal cancer (CRC) is a leading cause of cancer-related mortality globally, driven by heterogeneous signalling pathways. While the canonical NFκB pathway has been implicated in CRC progression, its therapeutic targeting has been limited by toxicity. This project focuses on the non-canonical NFκB pathway, specifically the kinase IKKα, which is associated with poor prognosis in CRC, particularly right-sided tumours. The study aims to characterise IKKα expression within the tumour microenvironment (TME), assess its spatial biology at the single-cell level, and evaluate its therapeutic potential using ex vivo models

Using multiplex immunofluorescence (mIF) on a large CRC tissue microarray (n=787), spatially resolved profiling of IKKα and immune markers will be performed. Visiopharm software will quantify marker coexpression and proximity analyses will identify immune cell interactions with IKKα-positive tumour cells. Spatial transcriptomics via NanoString CosMx™ will provide single-cell gene expression data to uncover biological differences linked to IKKα expression. Finally, patient-derived organoids will be used to test selective IKKα inhibition, with drug responses correlated to clinical and molecular features.

This multidisciplinary approach integrates spatial proteomics, transcriptomics, and functional modelling to elucidate IKKα’s role in CRC and inform biomarker-driven therapeutic strategies.