Investigating the role of complement in predicting and modulating treatment resistance in refractory gastro-oesophageal cancers.

Kirstan Murphy

Kristan was awarded a Musgrave PhD Scholarship in partnership with Breakthrough Cancer Research, under the supervision of Dr. Niamh Lynam-Lennon in Trinity College Dublin.

In Ireland each year, over a thousand patients are diagnosed with gastro-oesophageal cancer, which affects the stomach and the food pipe. Unfortunately, these cancers have a poor survival rate. Patients are treated with radiotherapy and/or chemotherapy drugs, which aim to kill the tumour cells, followed by surgery. Unfortunately, for many patients, these treatments do not work as their tumour has developed ways to resist treatment. Currently, there is no test to inform doctors, which patients will benefit from these treatments, and there are no current treatments that prevent tumours from becoming resistant

My research project aims to help gastro-oesophageal patients by understanding if we can use the complement system, a key part of the immune system as;

(i) a marker to predict, which patients will benefit from radiation and chemotherapy and

(ii) identify new treatment approaches to prevent tumours from becoming resistant to radiation and chemotherapy.

To do this, I will measure the levels of complement proteins in tumour and blood samples from gastro-oesophageal cancer patients to see if levels are increased in patients who have tumours that are resistant to radiation and chemotherapy. This will allow us to identify which patients will benefit from treatment and those who will not. Using gastro-oesophageal cancer cells grown in the lab, I will block complement to see if this prevents resistance and makes cancer cells more sensitive to radiation and chemotherapy. I will also investigate how complement is making cancer cells become resistant to these treatments. This will identify new treatment approaches for patients who are resistant to radiation and/or chemotherapy, which will improve treatment, quality of life, and survival for gastro-oesophageal cancer patients.