Associate Prof Jake Shortt receives Cancer Council Victoria funding for research into leukaemia and lymphoma treatments

Associate Professor Jake Shortt

Congratulations to Associate Professor Jake Shortt, Head of Haematology Research in the School of Clinical Sciences, who is the recipient of a Cancer Council Victoria 2020 Grants-in-Aid. The Cancer Council Victoria’s Grants-in-Aid program funds high-quality research projects into the treatment, causes, detection and prevention of all cancers.

Associate Professor Shortt, in collaboration with Dr Lev Kats from the Peter MacCallum Cancer Centre, received funding for their project 'Determining the reasons why leukaemia and lymphoma become resistant to treatments that alter the methylation of cancer DNA'

The Grants-in-Aid program supports research for 1 to 3 years, with applicants undergoing a rigorous peer-review process.

Associate Professor Shortt said, “The grant supports our work which seeks to determine mechanisms of resistance to (and subsequent treatment failure) a class of epigenetic drugs called 'hypomethylators' (or HMAs). Even very low doses of HMA have the capacity to remove methyl groups from the DNA of cancer cells and this seems to reset the aberrant gene expression programs that are required for the maintenance of certain malignancies.”

Currently, HMAs are approved for the treatment of a pre-leukaemic bone marrow failure syndrome called myelodysplasia (MDS) and subsequent acute myeloid leukaemia (AML). Professor Shortt and Dr Kats have determined that MDS/AML share certain molecular features relating to DNA methylation with T-cell lymphoma and so have successfully re-purposed HMAs for T-cell lymphoma treatments.

“This culminated in our own investigator initiated trial of a 'next generation' HMA called guadecitabine in T-cell lymphoma which has recently completed accrual at Monash Health and Concord Hospital in NSW,” said Associate Professor Shortt.

Unfortunately, despite dramatic initial responses to HMAs in many patients with MDS, AML and T-cell lymphoma all patients subsequently appear to relapse after a period of months to years. Associate Professor Shortt says they want to understand why, and develop new strategies to prevent HMA failure.

“Our CCV grant will use a combination of sophisticated CRISPR-based screening technologies and samples from patients treated with HMAs to determine mechanisms of HMA resistance - and ultimately try to circumvent these. The information we will gain will inform future drug combinations to be deployed with HMAs to prevent or overcome treatment failure,” Associate Professor Shortt said.