Notch Signaling: A Potential Therapeutic Target for Hematologic Malignancies
Notch Signaling: A Potential Therapeutic Target for Hematologic Malignancies
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DOI：
10.1615/critreveukaryotgeneexpr.2016016587
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发表时间：
2016-01-01
影响因子：
1.6
通讯作者：
Lin, Mei
中科院分区：
文献类型：
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作者：
Gao, Lingbao;Yuan, Keyu;Lin, Mei
Notch信号在胚胎发育中是一个保守的细胞命运决定因素，该信号的异常调节经常在许多类型的癌症中观察到，包括血液系统恶性肿瘤。在这篇综述中，我们简要描述了Notch信号通路，并主要关注Notch与血液系统恶性肿瘤的关系。我们还讨论了有前景的药物的临床发展，包括伽玛分泌酶抑制剂(GSI)和单抗(MAbs)。在T细胞急性淋巴细胞性白血病(T-ALL)患者中观察到GSIS治疗的完全缓解。此外，最近的一项研究表明，靶向Notch1的直接、选择性辅助因子Zmiz1，而不是直接靶向Notch，可能有助于降低当前的靶向相关毒性。综上所述，我们总结了Notch信号在血液系统恶性肿瘤中的作用，并讨论了通过靶向Notch信号来治疗这些疾病的策略。
Notch signaling is a well-conserved cell-fate determining factor in embryo development, and the dyregulation of this signaling is frequently observed in many types of cancers, including hematological malignancies. In this review, we briefly describe the Notch signaling pathway, and we primarily focus on the relationship between Notch and hematological malignancies. We also discuss the clinical development of promising agents including gamma-secretase inhibitors (GSIs) and monoclonal antibodies (mAbs). Complete response has been observed among patients with T-cell acute lymphoblastic leukemia (T-ALL) when treated with GSIs. Furthermore, a recent study has suggested that targeting Zmiz1, a direct, selective cofactor of Notch1, rather than targeting Notch directly, maybe helpful to reduce the current target-related toxicities. Taken together, we summarize the role of Notch signaling in hematological malignancies and discuss the treatment strategies for these diseases through targeting Notch signaling.