Notch inhibitors for cancer treatment

Abstract

Notch signaling is an evolutionarily conserved cell signaling pathway involved in cell fate during development, stem cell renewal and differentiation in postnatal tissues. Roles for Notch in carcinogenesis, in the biology of cancer stem cells and tumor angiogenesis have been reported. These features identify Notch as a potential therapeutic target in oncology. Based on the molecular structure of Notch receptor, Notch ligands and Notch activators, a set of Notch pathway inhibitors have been developed. Most of these inhibitors had shown anti-tumor effects in preclinical studies. At the same time, the combinatorial effect of these inhibitors with current chemotherapeutical drugs still under study in different clinical trials. In this review, we describe the basics of Notch signaling and the role of Notch in normal and cancer stem cells as a logic way to develop different Notch inhibitors and their current stage of progress for cancer patient’s treatment.

Jagged1 DNA Copy Number Variation Is Associated with Poor Outcome in Liver Cancer

“…To 10,11 . L-685,458 strongly inhibits amyloid beta, thus it is widely used in basic research, while DAPT has similar inhibitory effects but needs a greater concentration to inhibit signal peptide peptidase (SPP) 12,13 .…”

Oncogenic role of the Notch pathway in primary liver cancer

“…Mice with liver-specific constitutive activation of Notch1 intracellular domain (N1ICD) may develop HCC when they reach adult age (77). Genomic profiling technology has revealed that a Notch-specific gene expression signature reported in mice overexpressing NICD was also present in a cluster of patients with HCC (78). Histological analyses of the mouse liver tissue exhibited similar features compared with that of the HCC patients, which included the presence of proliferating K-19 positive cells.…”

Epithelial-mesenchymal transition-associated microRNAs in colorectal cancer and drug-targeted therapies (Review)

“…gSIs are the most widely studied Notch receptors, having potential for bio-distribution and pan-Notch inhibition (125). gSIs are utilized in Phase I clinical trials as a monotherapy or in combination with other drugs (126). Therefore Notch is a potential antitumor therapeutic target and its implementation should occur subsequent to in-depth study with a focus on the Notch signaling pathway.…”