Journal
EXPERT OPINION ON THERAPEUTIC TARGETS
Volume 26, Issue 6, Pages 547-556Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/14728222.2022.2083957
Keywords
Leukemic stem cell; acute myeloid leukemia; targeted therapy; hematopoiesis
Categories
Funding
- IRG CD200 Stem Cell Spec Mech - Overexpression of CD200 is a Stem Cell-Specific Mechanism of Immune Evasion in AML
- CCSG [P30 CA016672]
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As our understanding of the intricate pathophysiology of LSCs continues to grow, it is clear that targeting such heterogenous cells successfully will require a thoughtful and multi-modal approach.
Introduction Despite advances in the treatment of acute myeloid leukemia (AML), long-term survival remains low. In 1994, it was proposed that leukemic stem cells (LSCs) played a key role in relapsed and refractory disease. LSCs are capable of self-renewal, proliferation, differentiation, immune evasion, and drug resistance through several unique mechanisms. More recent leukemia drug development initiatives have included efforts to target LSCs. With LSCs, the challenge with such drug design is finding a way to selectively target LSCs while sparing normal hematopoietic stem cells (HSCs). Areas covered In this review, we explore the evolving knowledge of the unique LSC biology and physiology in the scientific literature, while noting the several agents that have been designed throughout the years to target this subgroup of leukemic cells. Our review includes discussion on chimeric antigen receptor T cells, monoclonal antibodies, antibody-drug conjugates against cell surface markers, signaling pathway targets, pro-apoptotic agents, epigenetic regulators, and more. Expert opinion As our understanding of the intricate pathophysiology of LSCs continues to grow, it is clear that targeting such heterogenous cells successfully will require a thoughtful and multi-modal approach.
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