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Notch Signaling Pathway in Carcinogenesis

  • Andrei Zlobin
  • Jeffrey C. Bloodworth
  • Andrew T. Baker
  • Clodia Osipo
Chapter

Abstract

The Notch signaling pathway is a highly conserved pathway in most multicellular organisms. It is of critical importance for cell proliferation, differentiation, and homeostasis. Aberrant Notch signaling can give rise to a number of pathologies including cancer. The Notch signaling pathway consists of a well-orchestrated series of biochemical events that provide multiple avenues for rational drug design. Design of targeted therapies focusing on Notch signaling is rapidly advancing. This review will aim to discuss the established and recent approaches to targeting the Notch pathway.

Keywords

Notch Cancer Gamma secretase Development Stem cell 

Notes

Conflict of Interest

The authors have no conflict of interest.

References

  1. 1.
    Yamamoto S, Schulze KL, Bellen HJ. Introduction to notch signaling. Methods Mol Biol. 2014;1187:1–14.CrossRefGoogle Scholar
  2. 2.
    Braune EB, Lendahl U. Notch – a goldilocks signaling pathway in disease and cancer therapy. Discov Med. 2016;21(115):189–96.PubMedPubMedCentralGoogle Scholar
  3. 3.
    Espinoza I, et al. Notch signaling: targeting cancer stem cells and epithelial-to-mesenchymal transition. Onco Targets Ther. 2013;6:1249–59.PubMedPubMedCentralGoogle Scholar
  4. 4.
    Fitzgerald K, Harrington A, Leder P. Ras pathway signals are required for notch-mediated oncogenesis. Oncogene. 2000;19(37):4191–8.CrossRefPubMedGoogle Scholar
  5. 5.
    Rizzo P, et al. Rational targeting of notch signaling in cancer. Oncogene. 2008;27(38):5124–31.CrossRefPubMedGoogle Scholar
  6. 6.
    Espinoza I, Miele L. Notch inhibitors for cancer treatment. Pharmacol Ther. 2013;139(2):95–110.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Fender AW, et al. Notch-1 promotes stemness and epithelial to mesenchymal transition in colorectal cancer. J Cell Biochem. 2015;116(11):2517–27.CrossRefPubMedGoogle Scholar
  8. 8.
    Panneerselvam J, Munshi A, Ramesh R. Molecular targets and signaling pathways regulated by interleukin (IL)-24 in mediating its antitumor activities. J Mol Signal. 2013;8(1):15.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Pannuti A, et al. Targeting notch to target cancer stem cells. Clin Cancer Res. 2010;16(12):3141–52.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Even C, et al. Notch pathway inhibition with LY3039478 in adenoid cystic carcinoma (ACC). J Clin Oncol. 2017;35(suppl; abstr 6024).CrossRefGoogle Scholar
  11. 11.
    Chiorean EG, et al. A phase I first-in-human study of enoticumab (REGN421), a fully human delta-like ligand 4 (Dll4) monoclonal antibody in patients with advanced solid tumors. Clin Cancer Res. 2012;21(12):2695–703.CrossRefGoogle Scholar
  12. 12.
    Kavalerchik E, et al. An open-label study of rovalpituzumab tesirine in patients with DLL3-expressing advanced solid tumors. J Clin Oncol. 2017;35(suppl; abstr TPS2597).CrossRefGoogle Scholar
  13. 13.
    Caffo M, et al. Innovative therapeutic strategies in the treatment of brain metastases. Int J Mol Sci. 2013;14(1):2135–74.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Takebe N, Nguyen D, Yang SX. Targeting notch signaling pathway in cancer: clinical development advances and challenges. Pharmacol Ther. 2014;141(2):140–9.CrossRefPubMedGoogle Scholar
  15. 15.
    Nowell CS, Radtke F. Notch as a tumor suppressor. Nat Rev Cancer. 2017;17:145–59.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Andrei Zlobin
    • 1
  • Jeffrey C. Bloodworth
    • 2
  • Andrew T. Baker
    • 3
  • Clodia Osipo
    • 4
  1. 1.Oncology Research InstituteLoyola University Medical CenterMaywoodUSA
  2. 2.Cardinal Bernardin Cancer CenterLoyola University ChicagoMaywoodUSA
  3. 3.Department of Integrative Cell BiologyLoyola University ChicagoMaywoodUSA
  4. 4.Department of Microbiology and ImmunologyStritch School of Medicine, Cardinal Bermardin Cancer Center of Loyola University ChicagoMaywoodUSA

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