Next Article in Journal
Prediction of Posterior Paraglottic Space and Cricoarytenoid Unit Involvement in Endoscopically T3 Glottic Cancer with Arytenoid Fixation by Magnetic Resonance with Surface Coils
Next Article in Special Issue
Fenofibrate Augments the Sensitivity of Drug-Resistant Prostate Cancer Cells to Docetaxel
Previous Article in Journal
Acknowledgement to Reviewers of Cancers in 2018
Previous Article in Special Issue
The Unfolded Protein Response in Breast Cancer
Article Menu
Issue 1 (January) cover image

Export Article

Open AccessReview
Cancers 2019, 11(1), 66; https://doi.org/10.3390/cancers11010066

Targeting Proteotoxic Stress in Cancer: A Review of the Role that Protein Quality Control Pathways Play in Oncogenesis

1
UCD Conway Institute of Biomolecular and Biomedical Science, Dublin, Dublin 4, Ireland
2
UCD School of Medicine, College of Health and Agricultural Sciences, University College Dublin, Belfield Dublin, Dublin 4, Ireland
3
LeBow Institute for Myeloma Therapeutics and Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
4
Biology Department, National University of Ireland Maynooth, Co. Kildare W23 F2K8, Ireland
5
Department of Hematology, Sichuan University, Chengdu, Sichuan 610041, China
6
Haematology Department, Mater Misericordiae University Hospital, Dublin Dublin 7, Ireland
*
Authors to whom correspondence should be addressed.
These authors contributed equally.
Received: 2 November 2018 / Revised: 24 November 2018 / Accepted: 7 December 2018 / Published: 9 January 2019
(This article belongs to the Special Issue Cellular Stress in Cancer Progression, Drug Resistance and Treatment)
Full-Text   |   PDF [1172 KB, uploaded 15 January 2019]   |  

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. View Full-Text
Keywords: proteotoxic stress; chemoresistance; proteasome; unfolded protein response; autophagy; multiple myeloma; triple negative breast cancer; protein quality control proteotoxic stress; chemoresistance; proteasome; unfolded protein response; autophagy; multiple myeloma; triple negative breast cancer; protein quality control
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
SciFeed

Share & Cite This Article

MDPI and ACS Style

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.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Cancers EISSN 2072-6694 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top