Ho Zhi Guang, Matthew and Kavanagh, Emma L. and Dunne, Luke Paul and Dowling, Paul and Zhang, Li and Lindsay, Sinéad and Bazou, Despina and Goh, Chia Yin and Hanley, Cathal and Bianchi, Giada and Anderson, Kenneth C. and O'Gorman, Peter and McCann, Amanda
(2019)
Targeting Proteotoxic Stress in Cancer: A Review of the Role that Protein Quality Control Pathways Play in Oncogenesis.
Cancers, 11 (66).
ISSN 2072-6694
Abstract
Despite significant advances in cancer diagnostics and therapeutics the majority of cancer
unfortunately remains incurable, which has led to continued research to better understand its
exceptionally diverse biology. As a result of genomic instability, cancer cells typically have elevated
proteotoxic stress. Recent appreciation of this functional link between the two secondary hallmarks
of cancer: aneuploidy (oxidative stress) and proteotoxic stress, has therefore led to the development
of new anticancer therapies targeting this emerging “Achilles heel” of malignancy. This review
highlights the importance of managing proteotoxic stress for cancer cell survival and provides an
overview of the integral role proteostasis pathways play in the maintenance of protein homeostasis.
We further review the efforts undertaken to exploit proteotoxic stress in multiple myeloma (as an
example of a hematologic malignancy) and triple negative breast cancer (as an example of a solid
tumor), and give examples of: (1) FDA-approved therapies in routine clinical use; and (2) promising
therapies currently in clinical trials. Finally, we provide new insights gleaned from the use of
emerging technologies to disrupt the protein secretory pathway and repurpose E3 ligases to achieve
targeted protein degradation.
Item Type: |
Article
|
Additional Information: |
© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access
article distributed under the terms and conditions of the Creative Commons Attribution
(CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Cite as: Ho Zhi Guang, M.; Kavanagh, E.L.; Dunne, L.P.; Dowling, P.; Zhang, L.; Lindsay, S.; Bazou, D.; Goh, C.Y.; Hanley, C.; Bianchi, G.; Anderson, K.C.; O’Gorman, P.; McCann, A. Targeting Proteotoxic Stress in Cancer: A Review of the Role that Protein Quality Control Pathways Play in Oncogenesis. Cancers 2019, 11, 66.
Funding: Funding is acknowledged from the UCD Wellcome Institutional Strategic Support Fund, which was
financed jointly by University College Dublin and the SFI-HRB-Wellcome Biomedical Research Partnership
(ref 204844/Z/16/Z) (A.M. and S.L). Funding is also acknowledged from The Mater Foundation, Mater
Misericordiae University Hospital (MMUH) Dublin Ireland (E.L.K). |
Keywords: |
proteotoxic stress; chemoresistance; proteasome; unfolded protein response; autophagy;
multiple myeloma; triple negative breast cancer; protein quality control; |
Academic Unit: |
Faculty of Science and Engineering > Biology |
Item ID: |
13579 |
Identification Number: |
https://doi.org/10.3390/cancers11010066 |
Depositing User: |
Paul Dowling
|
Date Deposited: |
18 Nov 2020 16:33 |
Journal or Publication Title: |
Cancers |
Publisher: |
MDPI |
Refereed: |
Yes |
Funders: |
UCD Wellcome Institutional Strategic Support Fund, The Mater Foundation, Mater Misericordiae University Hospital (MMUH) |
URI: |
|
Use Licence: |
This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available
here |
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