Department of Genetics, Louisiana State University Health Sciences Center, New Orleans, LA, USA.
Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, LA, USA.
Nat Rev Drug Discov. 2021 Feb;20(2):125-144. doi: 10.1038/s41573-020-00091-3. Epub 2020 Dec 8.
Notch signalling is involved in many aspects of cancer biology, including angiogenesis, tumour immunity and the maintenance of cancer stem-like cells. In addition, Notch can function as an oncogene and a tumour suppressor in different cancers and in different cell populations within the same tumour. Despite promising preclinical results and early-phase clinical trials, the goal of developing safe, effective, tumour-selective Notch-targeting agents for clinical use remains elusive. However, our continually improving understanding of Notch signalling in specific cancers, individual cancer cases and different cell populations, as well as crosstalk between pathways, is aiding the discovery and development of novel investigational Notch-targeted therapeutics.
Notch 信号通路参与癌症生物学的多个方面,包括血管生成、肿瘤免疫和癌症干细胞样细胞的维持。此外, Notch 在不同的癌症中和同一肿瘤内的不同细胞群体中可以作为癌基因和肿瘤抑制因子发挥作用。尽管有很有前景的临床前结果和早期临床试验,但开发安全、有效、肿瘤选择性 Notch 靶向药物用于临床应用的目标仍然难以实现。然而,我们对特定癌症、个别癌症病例和不同细胞群体中 Notch 信号通路以及途径之间相互作用的理解不断提高,这有助于发现和开发新的 Notch 靶向治疗药物。