Aberrant Notch signaling has been found in a broad range of human malignancies. Consequently, small molecule inhibitors and antibodies targeting Notch signaling in human cancers have been developed and tested; however, these have failed due to limited anti-tumor efficacy because of dose-limiting toxicities in normal tissues. Therefore, there is an unmet need to discover novel regulators of malignant Notch signaling, which do not affect Notch signaling in healthy tissues. This review provides a comprehensive overview of the current knowledge on the role of intracellular trafficking in ligand-independent Notch receptor activation, the possible mechanisms involved, and possible therapeutic opportunities for inhibitors of intracellular trafficking in Notch targeting.

中文翻译：

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Notch 受体细胞内转运在不依赖配体的 Notch 激活中的作用

在广泛的人类恶性肿瘤中发现了异常的 Notch 信号。因此，针对人类癌症中 Notch 信号传导的小分子抑制剂和抗体已经开发和测试。然而，由于正常组织中的剂量限制性毒性，这些药物由于抗肿瘤功效有限而失败。因此，发现新的恶性 Notch 信号调节剂的需求尚未得到满足，这些调节剂不会影响健康组织中的 Notch 信号传导。本综述全面概述了当前关于细胞内转运在配体非依赖性 Notch 受体激活中的作用、可能涉及的机制以及细胞内转运抑制剂在 Notch 靶向中可能的治疗机会的知识。