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Researchers in the Shi group at Ludwig Cancer Research Oxford have developed a new combination therapy for acute myeloid leukaemia, showing therapeutic promise by promoting differentiation of immature blood cells.

cancer research in lab

The histone demethylase LSD1, first discovered by Professor Yang Shi’s lab at Ludwig Cancer Research Oxford nearly two decades ago, has been widely studied for its role in the maintenance and proliferation of leukaemia stem cells in acute myeloid leukaemia (AML). AML is a type of blood cancer where white blood cells fail to mature, or differentiate, into functional cells. Several LSD1 inhibitors have been developed and tested in clinical trials, but their progress has been limited due to toxicity concerns identified in clinical settings.

Amir Hosseini, Abhinav Dhall, and colleagues in the Shi group have discovered a promising combination therapy for AML. This therapy involves the simultaneous inhibition of LSD1 and the signalling pathway regulator GSK3, to synergistically rewire the transcriptional program by suppressing the oncogenic Wnt/β-catenin pathway and stemness, while enhancing AML differentiation.

This approach enhanced the differentiation of leukemic cells, suppressed cancer growth, reduced tumour burden, and extended survival.

The findings of this study highlight the promise of this therapeutic strategy for AML and potentially other Wnt-driven cancers, providing a strong rationale for its further investigation in clinical settings.

To learn more about this work, please see the full article on the Nature website: https://www.nature.com/articles/s41586-025-08915-1