Novel Metabolic Therapies for Cancers

The metabolic enzymes isocitrate dehydrogenase 1 (IDH1) and 2 (IDH2) are mutated in numerous cancers, including acute myeloid leukemia, myelodysplastic syndromes, glioma, T-cell acute lymphoblastic leukemia, chondrosarcoma, and cholangiocarcinoma.

The discovery of these key drivers of cancer has offered hope that many tumours may be curable by metabolic therapy.

Using a range of technical approaches, we have discovered a number of metabolic vulnerabilities that block growth of these cancers. These include a low lipid diet, blockade of lipid enzymes and blockade of mitochondrial function at the level of the electron transport chain, complex I. Generous South Australian philanthropists (Seeley International & Richard Cavill Foundation) have enabled us to invest in world-class mass spectrometry equipment to discover new metabolic pathways in cancer cells. This equipment will be available to all South Australian researchers from June 2023, located on Level 6 north in the Metabolomics and MS-Imaging Core Facility run by Marten Snel.

We are currently screening for novel metabolic treatments for IDH2 mutant cancers and combining small molecule and precision dietetic approaches for other common cancer mutations. An update of our projects will be presented at upcoming Cancer Metabolism meeting (SAHMRI, May 2024) and New Directions in Leukaemia Research (March 2024). We hope to test our findings in combination with proton therapy for patients with solid tumours such as brain cancers that have IDH1 mutations.

PARTNERING INSTITUTIONS

Centre for Cancer Biology, The University of South Australia

This project is funded by the Leukemia and Lymphoma Society and undertaken with the financial support of Cancer Council's Beat Cancer Project on behalf of its donors and the State Government through the Department of Health