期刊
AMERICAN JOURNAL OF HEMATOLOGY
卷 93, 期 4, 页码 553-563出版社
WILEY
DOI: 10.1002/ajh.25027
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资金
- Charif Souki Cancer Research Fund
- MD Anderson Cancer Centre Support Grant (CCSG) [CA016672]
- MD Anderson Cancer Center Leukemia SPORE [CA100632]
Despite significant advances in deciphering the molecular and cytogenetic pathways governing acute myeloid leukemia, improvements in treatment strategies and clinical outcomes have been limited. The discovery of FLT3 pathway and its potential role in leukemogenesis has generated excitement in the field and has provided a potential target for drug development. Despite setbacks encountered with first-generation inhibitors, we are witnessing an outbreak of novel agents with potent activity and improved pharmacodynamics which continue to generate promising results. The disease, however, remains a challenge to both patients and physicians with rapid emergence of resistance and subsequent treatment failure. Multiple unanswered questions remain as to which are the optimal FLT3-inhibitors and which strategies and combinations are likely to overcome resistance. This review revisits the development of FLT3-inhibitors, the pathways incriminated in their failure and summarizes available molecularly-designed strategies to design better clinical trials.
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