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Ho et al. J Cancer Metastasis Treat 2019;5:70 Journal of Cancer
DOI: 10.20517/2394-4722.2019.25 Metastasis and Treatment

Review Open Access

Exploiting autophagy in multiple myeloma

Matthew Ho 1,2,# , Ashish Patel , Cathal Hanley , Adam Murphy , Tara McSweeney , Li Zhang , Amanda
3
1
1
1,#
1
McCann , Peter O’Gorman , Giada Bianchi 5
4
1,2
1 UCD School of Medicine, College of Health and Agricultural Sciences, University College Dublin, Belfield Dublin, Dublin 4,
Ireland.
2 UCD Conway Institute of Biomolecular and Biomedical Science, Dublin, Dublin 4, Ireland.
3 Department of Hematology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.
4 Haematology Department, Mater Misericordiae University Hospital, Dublin, Dublin 7, Ireland.
5 LeBow Institute for Myeloma Therapeutics and Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology,
Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
# These authors contributed equally.
Correspondence to: Dr. Giada Bianchi, Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School,
440 Brookline Avenue, Boston, MA 02215, USA. E-mail: giada_bianchi@dfci.harvard.edu

How to cite this article: Ho M, Patel A, Hanley C, Murphy A, McSweeney T, Zhang L, McCann A, O’Gorman P, Bianchi G. Exploiting
autophagy in multiple myeloma. J Cancer Metastasis Treat 2019;5:70. http://dx.doi.org/10.20517/2394-4722.2019.25

Received: 18 Aug 2019 First Decision: 12 Oct 2019 Revised: 12 Oct 2019 Accepted: 15 Oct 2019 Published: 24 Oct 2019

Science Editor: Chun Hei Antonio Cheung Copy Editor: Cai-Hong Wang Production Editor: Jing Yu

Abstract

Multiple myeloma (MM) is a plasma cell cancer characterized by sustained endoplasmic reticulum (ER) stress and
unfolded protein response activation in the setting of high rates of immunoglobulin synthesis. Consequently, MM
cells rely heavily on protein quality control pathways for survival as evidenced by the clinical efficacy of proteasome
inhibitors (PI). Autophagy is an intracellular self-digestion mechanism that plays a role in the ER protein quality
control process. Unsurprisingly then, basal levels of autophagy were recently found to confer a survival and drug-
resistance benefit to MM cells. However, excessive induction of autophagy in MM cells leads to autophagic cell
death, highlighting the double-edged nature of autophagy modulation in MM. This review provides an overview of
the role that autophagy plays in MM pathogenesis, survival, and drug-resistance. We highlight the potential utility
of therapeutically targeting autophagy in MM, focusing on preclinical data of autophagic modulators in combination
with alkylators, anthracyclines, PI, and immunomodulatory drugs.

Keywords: Multiple myeloma, autophagy, drug resistance, hematopoiesis, immunoglobulin, antibody

© The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license,
and indicate if changes were made.

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