Precision medicine in AML: overcoming resistance.

Autor: Urrutia S; Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, 1901 East Road, 4SCR6.2085, Houston, TX, 77030-4009, USA., Takahashi K; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, USA. ktakahashi@mdanderson.org.
Jazyk: angličtina
Zdroj: International journal of hematology [Int J Hematol] 2024 Oct; Vol. 120 (4), pp. 439-454. Date of Electronic Publication: 2024 Aug 01.
DOI: 10.1007/s12185-024-03827-8
Abstrakt: The development of molecularly targeted therapy for acute myeloid leukemia is progressing at an accelerated pace. Therapies targeting FLT3, IDH1, IDH2, and BCL2 have been approved in the last 5 years. As we exploit these biological vulnerabilities, various mechanisms of resistance arise. Emergence of competing clones with different genetic drivers and acquisition of constitutional mutations in the target renders therapies ineffective, and enzymatic isoform changes can lead to reappearance of the disease phenotype. Understanding the timing and circumstances of resistance origination will allow clinicians to develop combinatorial and sequential therapeutic approaches to deepen responses and improve survival. The objective of this review is to illustrate the biological underpinnings of each therapy and the landscape of resistance mechanisms and discuss strategies to overcome on- and off-target resistance.
(© 2024. Japanese Society of Hematology.)
Databáze: MEDLINE
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