Bowel Cancer Research

‘Characterising Colorectal Metastases and Optimising their Management’

Peter MacCallum Cancer Centre, VIC
Awarded 2019
Rotary Club of Keilor ‘Judith Annette Thompson’ PhD Scholarship

“As a surgeon, I was frustrated by the number of patients in whom the ‘standard cocktail’ of chemotherapy agents was not successful.”

Researcher Profile

I started medical school at the age of 16. I was actively involved in leadership activities and research throughout medical school. During clinical years, I initiated and coordinated surgical literature and technique based tutorials for medical students. I graduated in 2009 with an overall rated 1st Class Honours for the purpose of entry to the University of Melbourne PhD Program.

I obtained my general surgery fellowship in 2017.Following completion of my PhD, I will pursue further training in colorectal surgery. Subsequently, my long
term plan is to work in a tertiary centre as a colorectal surgeon with a university appointment to allow me to stay involved in ongoing research.

Project Summary

Colorectal cancer is the third most common cancer, and second leading cause of cancer death worldwide. Among those with metastatic disease, liver is the most common site for metastasis. Despite advances in the treatment of colorectal liver metastases (CRLM), recurrence rates reach up to 70%. About half of these patients are not amenable for treatment via local therapy.

Recently, anti-tumour responses have been seen with the use of immunotherapy, such as checkpoint inhibitors – PD-1/PD-L1 and CTLA-4 inhibitors. The impact of mucosal associated invariant T-cell (MAIT) infiltration has also been identified as having the potential to directly impact on tumour response to immunotherapy. This leads to the possibility of applying immunotherapy to the management of CRLM.

HYPOTHESIS
We hypothesise that colorectal liver metastasis have deranged pathway signalling that affect cell fate, differentiation and immune control. The identification of these pathways will lead to development of more focused therapies to improve the management of CRLM.

AIMS
Aim 1
Evaluate the immunological landscape of CRLM and their impact on chemotherapeutic drug sensitivity profiles.
Aim 2
Assess the pattern of MAIT infiltration in CRLM and their impact on immune profile.
Aim 3
Determine the response of CRLM to immune mediated killing, the impact of MAITs, and the impact of immunotherapy.

Supervisors: Professor Alexander Heriot & Professor Rob Ramsay