Enhancing Therapeutic Efficacy of FLT3 Inhibitors with Combination Therapy for Treatment of Acute Myeloid Leukemia

被引:1
作者
Leifheit, Malia E. [1 ]
Johnson, Gunnar [1 ]
Kuzel, Timothy M. [1 ]
Schneider, Jeffrey R. [2 ]
Barker, Edward [2 ]
Yun, Hyun D. [3 ,4 ]
Ustun, Celalettin [1 ]
Goldufsky, Josef W. [1 ]
Gupta, Kajal [5 ]
Marzo, Amanda L. [1 ]
机构
[1] Rush Univ, Med Ctr, Dept Internal Med, Div Hematol & Oncol & Cell Therapy, Chicago, IL 60612 USA
[2] Rush Univ, Med Ctr, Dept Microbial Pathogens & Immun, Chicago, IL 60612 USA
[3] Vet Affairs Long Beach Healthcare Syst, Hematol Oncol, Long Beach, CA 90822 USA
[4] Univ Calif Irvine, Sch Med, Dept Med, Div Hematol Oncol, Irvine, CA 92617 USA
[5] Rush Univ, Med Ctr, Dept Surg, Chicago, IL 60612 USA
关键词
acute myeloid leukemia (AML); gilteritinib; mTOR inhibitors; rapamycin; NK cells; NATURAL-KILLER-CELLS; CANCER STEM-CELLS; RISK MYELODYSPLASTIC SYNDROME; SUPERAGONIST COMPLEX ALT-803; ACUTE MYELOGENOUS LEUKEMIA; MINIMAL RESIDUAL DISEASE; RANDOMIZED PHASE-III; IN-VIVO EXPANSION; TGF-BETA; NK CELLS;
D O I
10.3390/ijms25179448
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
FMS-like tyrosine kinase 3 (FLT3) mutations are genetic changes found in approximately thirty percent of patients with acute myeloid leukemia (AML). FLT3 mutations in AML represent a challenging clinical scenario characterized by a high rate of relapse, even after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The advent of FLT3 tyrosine kinase inhibitors (TKIs), such as midostaurin and gilteritinib, has shown promise in achieving complete remission. However, a substantial proportion of patients still experience relapse following TKI treatment, necessitating innovative therapeutic strategies. This review critically addresses the current landscape of TKI treatments for FLT3+ AML, with a particular focus on gilteritinib. Gilteritinib, a highly selective FLT3 inhibitor, has demonstrated efficacy in targeting the mutant FLT3 receptor, thereby inhibiting aberrant signaling pathways that drive leukemic proliferation. However, monotherapy with TKIs may not be sufficient to eradicate AML blasts. Specifically, we provide evidence for integrating gilteritinib with mammalian targets of rapamycin (mTOR) inhibitors and interleukin-15 (IL-15) complexes. The combination of gilteritinib, mTOR inhibitors, and IL-15 complexes presents a compelling strategy to enhance the eradication of AML blasts and enhance NK cell killing, offering a potential for improved patient outcomes.
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页数:24
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