Bowel Cancer Research

‘Renin Angiotensin System (RAS) inhibitors combined with tumour resection in the treatment of colorectal cancer liver metastasis (CRCLM)’

University of Melbourne, VIC
Awarded 2019
Co-funded by Rotary District 9675 Bowelscan

“Cancer affects many people in our society without a cure. There are many question that still need to be answered before a cure is found.”

Researcher Profile

I have completed a Bachelor of Science (Honours), awarded in 2014. My Honours research project focused on the kinetics and activation states of macrophages in colorectal cancer liver metastases following treatment with OXi4503 a Vascular Disruptive Agent (VDA) treatment. While researching this topic I gained valuable experience in various experiments, in data collection and analysis and in research techniques such as using immunohistochemistry to determine treatment response.

My project involved mice and therefore I am familiar with the animal ethics and protocols of how to handle animal and recognise the different sign of their state of health.

Project Summary

In 2015 bowel or colorectal cancer (CRC) accounted for 9.7% of all cancer incidents in the world with approximately 814,000 cases in men and 664,000 cases in women making it the third most common cancer in men and the second in women. Liver is the most common site for CRC metastasis and occurs in more than 50% of all CRC patients. Currently liver resection supported with chemotherapy is the only treatment offering long term survival in patients with colorectal cancer liver metastasis (CRCLM). The success rate is limited by the capacity of the liver to regrow its mass and recover its function. This may be impaired by injury caused by the cancer and conventional chemotherapy. Additionally, factors involved in liver regrowth also contribute to tumour recurrence.

Therefore, new treatments that do not affect the process of liver regrowth but are able to inhibit tumour recurrence are needed. Inhibitors of the renin angiotensin system (RAS) are currently used in the clinic to control hypertension. Studies over the past few years have found that RAS inhibitors also have a beneficial impact in tumour occurrence and an inhibiting role in tumour progression. Numerous retrospective analyses have shown a reduction in CRC incidence, polyp formation and distant metastasis in patients taking inhibitors of the RAS system. Additionally experimental studies have shown that RAS inhibition speeds up liver regrowth while it retards tumour growth.

These findings highlight the potential of RAS inhibition as a novel strategy in the treatment of CRCLM to reduce liver injury and improve liver function during the critical early phases post-surgery while reducing the risk of tumour recurrence.

Supervisors: Professor Christopher Christophi, Dr Theodora Fifis & Dr Marcos Perini