Therapeutic approaches to modulating Notch signaling: current challenges and future prospects.
Therapeutic approaches to modulating Notch signaling: current challenges and future prospects.
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DOI：
10.1016/j.semcdb.2012.01.016
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发表时间：
2012-06
影响因子：
7.3
通讯作者：
Fortini, Mark E.
中科院分区：
文献类型：
--
作者：
Groth, Casper;Fortini, Mark E.
Notch信号失调与许多人类疾病有关，包括广泛的癌症。Notch1的突变在t细胞急性淋巴细胞白血病中普遍存在，不同人类Notch受体的异常表达有助于b细胞肿瘤以及乳腺癌、肺癌、胰腺癌、皮肤、前列腺癌、结肠癌、脑癌等组织癌的发生。几种γ-分泌酶抑制剂是一种小化合物，最初是为了抑制阿尔茨海默病中γ-分泌酶天冬氨酸蛋白酶的活性而开发的，现在正在探索它们在notch相关癌症的潜在化疗应用。另一种方法是开发抗体来抑制肿瘤中特定的Notch受体、其激活配体或Notch通路的其他组分。在这里，我们回顾了这些策略在癌症治疗中调节Notch信号的最新进展和当前的挑战。
Dysregulated Notch signaling has been implicated in numerous human diseases, including a broad spectrum of cancers. Mutations in Notch1 are prevalent in T-cell acute lymphoblastic leukemia, and abnormal expression of different human Notch receptors contributes to B-cell tumors as well as cancers of the breast, lung, pancreas, skin, prostate, colon, brain and other tissues. Several γ-secretase inhibitors, small chemical compounds that were initially developed to inhibit the activity of the γ-secretase aspartyl protease in Alzheimer’s disease, are now being explored for their potential chemotherapeutic applications in Notch-associated cancers. An alternative approach involves the development of antibodies to inhibit specific Notch receptors, their activating ligands, or other components of the Notch pathway in tumors. Here we review recent progress and current challenges in the use of these strategies to modulate Notch signaling for cancer therapy.
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