Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, USA.
Department of Biotechnology, Maharishi Markandeshwar (Deemed to be University), Mullana-Ambala, 133 207, Haryana, India.
Crit Rev Oncol Hematol. 2021 Aug;164:103403. doi: 10.1016/j.critrevonc.2021.103403. Epub 2021 Jun 29.
Notch signaling, an evolutionarily conserved signaling cascade, is critical for normal biological processes of cell differentiation, development, and homeostasis. Deregulation of the Notch signaling pathway has been associated with tumor progression. Thus, Notch presents as an interesting target for a variety of cancer subtypes and its signaling mechanisms have been actively explored from the therapeutic viewpoint. However, besides acting as an oncogene, Notch pathway can possess also tumor suppressive functions, being implicated in inhibition of cancer development. Given such interesting dual and dynamic role of Notch, in this review, we discuss how the evolutionarily conserved Notch signaling pathway drives hallmarks of tumor progression and how it could be targeted for a promising treatment and management of cancer. In addition, the up-to-date information on the inhibitors currently under clinical trials for Notch targets is presented along with how NOTCH inhibitors can be used in conjunction with established chemotherapy/radiotherapy regimes.
Notch 信号通路是一种进化上保守的信号级联反应，对细胞分化、发育和稳态的正常生物学过程至关重要。 Notch 信号通路的失调与肿瘤的进展有关。因此，Notch 成为各种癌症亚型的一个有趣的治疗靶点，其信号机制也从治疗的角度被积极探索。然而，除了作为致癌基因外，Notch 途径也可能具有肿瘤抑制功能，参与抑制癌症的发展。鉴于 Notch 的这种有趣的双重和动态作用，在这篇综述中，我们讨论了进化上保守的 Notch 信号通路如何驱动肿瘤进展的特征，以及如何针对该通路进行靶向治疗，以有希望治疗和管理癌症。此外，还介绍了目前在临床试验中针对 Notch 靶点的抑制剂的最新信息，以及如何将 NOTCH 抑制剂与现有的化疗/放疗方案联合使用。
