Can colorectal cancer phenotypic subtypes predict response to therapy?

Supervisors: Joanne Edwards (University of Glasgow), Owen Sansom (CRUK Beatson Institute)

We recently proposed phenotypic subtypes for CRC as a novel histology based subtyping method to stratify patient outcome. The subtypes are based on phenotypic characteristics of the tumour microenvironment (immune and stromal infiltrate) and tumour growth. They are classified into four subgroups: immune, canonical, latent and stromal and are extrapolated from the consensus molecular subtypes (CMS) proposed by Guinney et al. in 2015. These phenotypic subtypes independently stratified cancer-specific survival in a cohort of 859 patients with CRC and could easily translate to the diagnostic setting as a prognostic tool to aid clinicians in their decision making.

The aim of the current project is to establish if these phenotypic subtypes can also be employed as predictive tools. This will be achieved by assessing the ability to predict response to adjuvant chemotherapy in 1500 patients from the SCOT trial which compared 12 to 24 weeks adjuvant chemotherapy. In parallel novel targets and therapeutic strategies will be examined in Genetically Engineered and organoid models of CRC.

This project will establish if phenotypic subtypes can be employed as predictive tools in the clinic and heighten awareness of the potential to develop a personalised medicine approach for treating CRC.

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