Curing blood cancers: rapid translation from target to drug to clinic

Project: Research

Project Description

Cure rates for blood cancers such as acute leukemia, myelodysplasia and myeloproliferative neoplasms have changed little over the last 20 years. Building upon my seminal work in a mouse model of T-ALL, my talented research team coupled with academic collaborators will address three important goals: (1) identify ‘druggable’ targets within the Lmo2:Lyl1 oncogenic complex; (2) target pathways that maintain quiescence of leukemic cells, a fundamental property that allows them to evade chemotherapy; and (3) examine the therapeutic potential of Dynole, an inhibitor of receptor mediated endocytosis required for signalling pathways in leukemic cells. Through this work, we will identify new strategies of killing leukemic cells that could be rapidly tested in early phase I/II clinical trials within the next five years.

Partnering with the Cancer Therapeutics CRC (CTx), I initiated a small molecule screen for inhibitors of the protein arginine methyltransferase called PRMT5. In 2016, we published three patents and licensed these molecules to MERCK for an upfront fee of $AUD 21M. Unique access to these inhibitors together with a large commercial research collaboration will make us the first to examine the potential of these inhibitors for hematologic malignancies. Specifically, we will use these inhibitors to (1) identify the key substrates of PRMT5 in blood cancers using state of the art technologies; (2) test the activity of PRMT5 inhibitors on a large number of genetically defined mouse models and primary patient samples; and (3) use CRISPR screens to identify genes or pathways that confer sensitivity or resistance to PRMT5 inhibitors. Together, this will position me as an international leader for the first-in-human phase I/II clinical trials (2018/19) and trigger milestone payments of up to $30M to the CRC partners for re-investment in Australian drug development.
StatusActive
Effective start/end date1/01/1831/12/22

Funding

  • National Health & Medical Research Council (NHMRC): AUD707,370.00