Targeting TOPORS E3 Ligase to Overcome Resistance to Hypomethylating Therapy in AML

Professor John Pimanda

UNSW

$600,000

2026 - 2029

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Background:

Acute myeloid leukemia (AML) is an aggressive blood cancer that affects over 1,200 Australians each year with the five-year survival rate of ≤30%. 

Older patients can’t receive intensive treatments like high dose chemotherapy or a bone marrow transplant, so they are treated with medicines that help slow the disease and ease symptoms. Even with current best options, survival is often limited and outcomes are especially poor for people with TP53mutant AML, a hard-to-treat subtype. TP53 plays a critical role in preventing cancer, but when mutated, damaged cells can keep dividing and lead to cancer.

About the Project:

Prof John Pimanda and the team are aiming to help existing treatments work better for people with acute myeloid leukemia (AML), especially those who do not respond well to current medicines. The researchers have discovered that leukemia cells use a specific “survival switch” that makes treatments less effective.

The project will test new ways to turn off this survival switch, so leukemia cells become sensitive to treatment again. One approach uses tiny genetic messengers delivered inside small fat-based particles, to safely target cancer cells. A second approach explores small blocking molecules that interfere with how this survival switch works, helping guide the development of future medicines. These strategies will be tested in laboratory models that closely match human leukemia, with the goal of improving treatment response for patients with very limited options.

Impact:

This research leads to better treatment options for people with AML, particularly older patients and those whose cancer no longer responds to standard care. By helping existing medicines work more effectively, this approach could slow the disease and help patients live longer with a better quality of life.

In the longer term, this work aims to move quickly towards clinical trials, bringing new hope to people with aggressive forms of AML who currently have very limited options. It could also help doctors get more benefit from treatments already in use, potentially improving care for a wider range of cancer patients.

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