Skip to main page content
U.S. flag
See More

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2013 Aug;139(2):95-110.
doi: 10.1016/j.pharmthera.2013.02.003. Epub 2013 Feb 28.

Notch inhibitors for cancer treatment

Ingrid Espinoza  1 , Lucio Miele
Affiliations
Review

Notch inhibitors for cancer treatment

Ingrid Espinoza et al. Pharmacol Ther. 2013 Aug.

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 is 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.

PubMed Disclaimer

Conflict of interest statement

6. Conflict of interest/disclosures

No conflict of interest.

Figures

Fig. 1
Fig. 1
Notch receptors and ligands
Fig. 1
Fig. 1
Notch receptors and ligands
Fig 2
Fig 2
Notch signaling pathway
See this image and copyright information in PMC

References

    1. Acar M, Jafar-Nejad H, Takeuchi H, Rajan A, Ibrani D, Rana NA, et al. Rumi is a CAP10 domain glycosyltransferase that modifies Notch and is required for Notch signaling. Cell. 2008;132(2):247–258. - PMC - PubMed
    1. Agrawal N, Frederick MJ, Pickering CR, Bettegowda C, Chang K, Li RJ, et al. Exome sequencing of head and neck squamous cell carcinoma reveals inactivating mutations in NOTCH1. Science. 2011;333(6046):1154–1157. - PMC - PubMed
    1. Aguilera C, Hoya-Arias R, Haegeman G, Espinosa L, Bigas A. Recruitment of IkappaBalpha to the hes1 promoter is associated with transcriptional repression. Proc Natl Acad Sci U S A. 2004;101(47):16537–16542. - PMC - PubMed
    1. Albain K, Czerlanis C, Zlobin A, Covington KR, Rajan P, Godellas C, et al. Modulation of Cancer Stem Cell Biomarkers by the Notch Inhibitor MK0752 Added to Endocrine Therapy for Early Stage ER+ Breast Cancer. Cancer Res. 2011;71(24 Suppl):97s.
    1. Allen TD, Rodriguez EM, Jones KD, Bishop JM. Activated Notch1 induces lung adenomas in mice and cooperates with Myc in the generation of lung adenocarcinoma. Cancer Res. 2011;71(18):6010–6018. - PMC - PubMed

Publication types