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The research proposes to discover new medicine that improves azacitidine efficacy by using a novel chemical-genome screen using a MDS cell line to identify specific genes that can make MDS cells more sensitive to the medicine.
The most effective medicine to treat myelodysplastic syndrome (MDS), azacitidine, works in only half of MDS and associated AML patients who commence treatment. Over the past decade, Prof. Pimanda and his team have identified treatment alternatives for patients who have been proven, or have potential to be, non-responsive to azacitidine. The research proposes to discover new medicine that improves azacitidine efficacy by using a novel chemical-genome screen using a MDS cell line to identify specific genes that can make MDS cells more sensitive to the medicine. This information will then be used to identify molecular pathways amenable to pharmacological manipulation to achieve the same effect. Efficacy of medicine combinations in enhancing azacitidine activity can then be assessed, using azacitidine non-responder MDS cells to undertake pre-clinical testing in preparation for a future clinical trial.