Blood: Metabolic-based cancer treatment - Aldh3a2 inhibition
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Last Update: 2020-06-05
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Source: Internet
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Author: User
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Metabolic changes in cancer represent the aggregate effect of cancer-causing mutationsThe researchers hypothesized that in an in vitro system that simulated a bone marrow microenvironment, the unique weaknesses of acute myeloid leukemia (AML) could be identified by a genetic screening of normal mouse hematopoietic cells and malignant hematopoietic cells with limited metabolic restrictionsleukemia cells, but not normal bone marrow cells, relying on aldehyde dehydrogenase 3a2 (Aldh3a2); Aldehyde compounds are by-products of increased oxidation phosphorylation and nucleotide synthesis in cancer, produced by lipid peroxides, which are non-caspase-dependent forms of cell death, i.eiron poisoningthe dependence of leukemia cells on Aldh3a2 can be found in a variety of mice and human myeloid leukemiaAldh3a2 inhibition and glutathione peroxidase-4 (GPX4) inhibition are fatal for AML cells; GPX4 inhibition is a known iron function trigger with minimal effect on AML cellsin summary, inhibition of Aldh3a2 provides a therapeutic opportunity for AML to target malignant cells in unique metabolic states with a unique synthetic lethal mechanism
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