ArticleAnnals of medicine and surgery (2012)2026
Therapeutic advances in acute myeloid leukemia: from LSD1 blockade to PROTAC-based strategies.
Article in Annals of medicine and surgery (2012), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Acute myeloid leukemia (AML) is a fast-progressing blood cancer marked by immature myeloid cells and poor survival rates. Most AML subtypes resist standard treatments, especially in older adults, highlighting the need for new targeted therapies. A hallmark of AML is LSD1 overexpression, which blocks blood cell maturation. Though some LSD1 inhibitors can trigger differentiation, their use is limited by toxicity and incomplete target inhibition. PROTAC degraders like MS9117 offer a promising solution by eliminating LSD1. This halts leukemia growth, promotes robust cell differentiation, and restores sensitivity to agents like all-trans retinoic acid, benefits not seen with traditional inhibitors. PROTACs can also target previously undruggable proteins, such as transcription factors, potentially enabling lower doses and fewer side effects. Several PROTAC therapies are now in AML trials. LSD1-targeted degradation is promising, but further research is needed to confirm its safety, overcome resistance, and identify optimal drug combinations for AML treatment.
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