Inflammation-associated tumour promotion is a long-lasting process that, up to a point, can be reversed by therapeutic interference. Tumour promotion depends on the interaction of neoplastic cells with the microenvironment where excessive abundance of inflammatory mediators of the interleukin (IL-) 6/gp130 family promotes their expansion.
Although we established that genetic interference with Stat3 suppresses tumour promotion in our preclinical validated gp130F/F mouse model, Stat3 is a notoriously difficult molecule for therapeutic targeting. Surprisingly, we observed that administration of an mTor inhibitor reduced tumour burden, which at all stages remained dependent on PI3K/mTor signaling. We propose to:
The broad experimental expertise of the CIs with these models, the availability of the mouse strains and the proprietary small molecules ensures feasibility of these studies.
Collectively, these studies will highlight therapeutic opportunities for existing treatment modalities for inflammation-associated cancer for which there is currently limited availability of compounds that target non-redundant signalling components of the gp130/Stat3 network.
Dr Michael Buchert, A/Prof Matthias Ernst
Cancer Council Research Grant
Ludwig Institute for Cancer Research (Jan-Sept 2012) Walter and Eliza Hall Institute of Medical Research (Oct 2012-Dec 2014)
$100,000 in 2012, $97,184 pa in 2013 & 2014