Notch signaling is responsible for conveying messages between cells through direct contact, playing a pivotal role in tissue development and homeostasis. The modulation of Notch-related processes, such as cell growth, differentiation, viability, and cell fate, offer opportunities to better understand and prevent disease progression, including cancer. Currently, research efforts are mainly focused on attempts to inhibit Notch signaling in tumors with strong oncogenic, gain-of-function (GoF) or hyperactivation of Notch signaling. The goal is to reduce the growth and proliferation of cancer cells, interfere with neo-angiogenesis, increase chemosensitivity, potentially target cancer stem cells, tumor dormancy, and invasion, and induce apoptosis. Attempts to pharmacologically enhance or restore disturbed Notch signaling for anticancer therapies are less frequent. However, in some cancer types, such as squamous cell carcinomas, preferentially, loss-of-function (LoF) mutations have been confirmed, and restoring but not blocking Notch functions may be beneficial for therapy. The modulation of Notch signaling can be performed at several key levels related to NOTCH receptor expression, translation, posttranslational (proteolytic) processing, glycosylation, transport, and activation. This further includes blocking the interaction with Notch-related nuclear DNA transcription. Examples of small-molecular chemical compounds, that modulate individual elements of Notch signaling at the mentioned levels, have been described in the recent literature.
Notch信号通路通过细胞间直接接触传递信息，在组织发育与稳态维持中发挥关键作用。调控Notch相关过程——如细胞生长、分化、存活及命运决定——为深入理解并阻断疾病（包括癌症）进展提供了新思路。当前研究主要聚焦于在具有强致癌性、功能获得性突变或Notch信号过度激活的肿瘤中抑制该通路，旨在实现以下目标：抑制癌细胞生长增殖、干扰新生血管生成、增强化疗敏感性、潜在靶向癌症干细胞、调控肿瘤休眠与侵袭、诱导细胞凋亡。相比之下，通过药理学手段增强或恢复紊乱的Notch信号用于抗癌治疗的研究较为有限。然而在某些癌种（如鳞状细胞癌）中，功能缺失性突变已被证实存在，此时恢复而非阻断Notch功能可能更具治疗价值。Notch信号调控可在多个关键层面实施，涉及NOTCH受体的表达、翻译、翻译后（蛋白水解）加工、糖基化修饰、转运及激活过程，还包括阻断Notch相关核内DNA转录相互作用。近期文献已报道了能在上述层面调节Notch信号通路特定组分的小分子化合物实例。
Modulation of Notch Signaling by Small-Molecular Compounds and Its Potential in Anticancer Studies
肿瘤(癌症)患者之家