The role of the Renin Angiotensin System in tumour progression and recurrence following tumour resection

• 
  Professor
  Christopher Christophi

  c.christophi@unimelb.edu.au

  View researcher's webpage

Project Details

Colorectal liver metastasis (CRCLM) is responsible for over 90% of colorectal cancer deaths. Resection of CRCLM is the only treatment offering potential long term survival. The outcome is limited by inadequate functional liver remnant and tumour recurrence following surgery. Liver regeneration restores liver function however the molecular mechanisms in liver regeneration also stimulate tumour recurrence.

Our studies show that renin angiotensin system (RAS) inhibition enhanced liver regeneration and significantly inhibited tumour progression. Reduced local and systemic inflammation upon treatment suggest it to be a main mechanism for these results.

Researchers

• Professor Christopher Christophi, Head of department
• Dr Linh Nguyen, Postdoctoral Research Fellow
• Dr Marcos Perini, Junior Consultant, Senior Lecturer
• Dr Edith Gomez, Research Assistant

Funding

Brian Smith Endowment

AHMRF

Melbourne Research Grant Support Scheme

Research Outcomes

1. Koh SL, Ager E, Malcontenti-Wilson C, Muralidharan V, Christophi C. Blockade of the renin-angiotensin system improves the early stages of liver regeneration and liver function. J Surg Res. 2013 179(1):66–71. (11 citations by Google Scholar).
2. Koh, S. L., Ager, E. I., Costa, P. L., Malcontenti-Wilson, C., Muralidharan, V. & Christophi, C. 2014. Blockade of the renin-angiotensin system inhibits growth of colorectal cancer liver metastases in the regenerating liver. Clin Exp Metastasis.
3. Ager, E.I., Christophi, C et al., Altered efficacy of AT1R-targeted treatment after spontaneous cancer cell-AT1R upregulation. BMC Cancer, 2011. 11: p. 274.
4. Wen, S.W., E.I. Ager, J. Neo, C, Christophi et al., The renin angiotensin system regulates Kupffer cells in colorectal liver metastases. Cancer Biol Ther, 2013. 14(8): p. 720-7.
5. Nguyen L., Christophi, C et al., Regulation of colorectal cancer cell epithelial to mesenchymal transition by the renin angiotensin system. J Gastroenterol Hepatol, 2016.