In search of the mechanism of action of Fn14 in the production of a cachexic state

With the discovery that Fn14 in tumor cells and not in peripheral tissues, causes cachexia, and that the ligand of Fn14 is not required for the action of Fn14, we are seeking to discover the soluble factor released by the tumor responsible for the cachectic state in peripheral tissues. Further, the finding that the ligand TWEAK is not required for this process raises the question of the intracellular signalling components in the tumor cell. We aim to determine these details before we commence clinical trials.

This work will be prelude to pharmacokinetic and toxicological studies and testing in multiple preclinical models of cachexia. The work is funded by the Victorian Cancer Agency and involves a team of collaborators consisiting ofclinical oncologist, Professor Andrew Scott at the ONJCRI, Amelia Johnston, Hamsa Puthalakath, Megan Maher from LIMS and John Silke from the Walter and Eliza Hall Institute and Ulf Eriksson from the Karolinska Institute in Stockholm, Sweden.

Funding by:

Victorian Cancer Agency Translational grant. Principal Investigator, N.Hoogenraad, Associate investigators A. Scott, H. Puthalakath, A. Johnston, M. Maher, J. Silke and U. Eriksson. Understanding the Biological Basis of Cancer Cachexia. 2016: $1,300,000, 2017: $700,000. 2018: $466,000.

NHMRC Development grant 1117541. Chief Investigator, Nick Hoogenraad with Associated Investigators Andrew Scott, Hamsa Puthalakath, Amelia Johnston, John Silke and Megan Maher. Cancer cachexia Therapeutics. 2017: $330,840, 2018: $295,840.

Victorian Medical Research Acceleration Fund. Principal investigator Nick Hoogenraad. 2017-2018: $500,000.