Therapeutic Targeting of Amyloid Precursor Protein and its Processing Enzymes for Breast Cancer Treatment

Syed Mohd Danish Rizvi; Talib Hussain; Gehad M Subaiea; Shazi Shakil; Adnan Ahmad

doi:10.2174/1389203718666170828123924

Therapeutic Targeting of Amyloid Precursor Protein and its Processing Enzymes for Breast Cancer Treatment

Curr Protein Pept Sci. 2018;19(9):841-849. doi: 10.2174/1389203718666170828123924.

Authors

Syed Mohd Danish Rizvi¹, Talib Hussain¹, Gehad M Subaiea¹, Shazi Shakil^{2

3

4}, Adnan Ahmad⁵

Affiliations

¹ Department of Pharmacology and toxicology, College of Pharmacy, University of Hail, Hail, Saudi Arabia.
² Center of Innovation in Personalized Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
³ Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, P.O. Box 80216, Jeddah 21589, Saudi Arabia.
⁴ Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia.
⁵ Department of Bioengineering, Integral University, Lucknow 226026, India.

PMID: 28847292
DOI: 10.2174/1389203718666170828123924

Abstract

Breast cancer cases in women are increasing at an alarming rate globally and extensive research is being conducted to identify a breakthrough medicine against this dreadful disease. In fact, researchers are looking for fresh targets to develop novel treatment strategies for cancer of the breasts. In this article, 'amyloid precursor protein' or (APP) and its processing enzymes are deeply studied so as to explore the same as prospective targets for breast cancer treatment. Even though most of the studies on APP and its processing enzymes have been performed on neuronal cells owing to their linkage with Alzheimer's disease, they are omnipresent on various non-neuronal cells also. Interestingly, APP and its processing enzymes have a role in the proliferation of cancer cells as well as in their growth, adherence and movement. Over-synthesis of APP and its processing enzymes are emerging as important hallmark features in breast cancer. It has been found that APP and its processing enzymes, i.e., γ-secretase and α- secretase are strongly linked with breast cancer via Akt phosporylation and Notch signaling pathways. Thus, targeting APP or γ-secretase or α-secretase could be considered as an effective strategy to treat breast cancer and even metastasis. There are various clinical trials which are in progress to explore the potential of γ-secretase inhibitor against breast cancer. Hence, the present review is composed of two sections, one section deals with all the possible linkages of APP and APP processing enzymes (α- secretase, β-secretase and γ-secretase) with breast cancer. However, the other section provides recent information on breast cancer treatment strategy using APP and APP processing enzymes as targets. We strongly believe that compilation of these studies would be beneficial to the scientist working in the field of 'breast cancer-treatment'.

Keywords: ADAM's; Akt phosphorylation; Breast cancer; amyloid precursor protein; notch signaling; γ-secretase inhibitor..

Publication types

Review

MeSH terms

Amyloid Precursor Protein Secretases / antagonists & inhibitors
Amyloid Precursor Protein Secretases / metabolism*
Amyloid beta-Peptides / metabolism
Amyloid beta-Protein Precursor / metabolism*
Antineoplastic Agents / therapeutic use*
Breast Neoplasms / metabolism
Breast Neoplasms / therapy*
Female
Humans
Molecular Targeted Therapy / methods*
Phosphorylation

Substances

Amyloid beta-Peptides
Amyloid beta-Protein Precursor
Antineoplastic Agents
Amyloid Precursor Protein Secretases