Therapeutic Targeting of Cancer Stem Cells in Human Glioblastoma by Manipulating the Renin-Angiotensin System

David Ch Tan; Imogen M Roth; Agadha C Wickremesekera; Paul F Davis; Andrew H Kaye; Theo Mantamadiotis; Stanley S Stylli; Swee T Tan

doi:10.3390/cells8111364

Therapeutic Targeting of Cancer Stem Cells in Human Glioblastoma by Manipulating the Renin-Angiotensin System

Cells. 2019 Oct 31;8(11):1364. doi: 10.3390/cells8111364.

Authors

David Ch Tan¹, Imogen M Roth², Agadha C Wickremesekera^{3

4

5}, Paul F Davis⁶, Andrew H Kaye^{7

8}, Theo Mantamadiotis⁹, Stanley S Stylli^{10

11}, Swee T Tan^{12

13

14}

Affiliations

¹ Department of Neurosurgery, Wellington Regional Hospital, Wellington 6021, New Zealand. Tan.David@ccdhb.org.nz.
² Gillies McIndoe Research Institute, Wellington 6021, New Zealand. imogen.roth@gmri.org.nz.
³ Department of Neurosurgery, Wellington Regional Hospital, Wellington 6021, New Zealand. Agadha.Wickremesekera@ccdhb.org.nz.
⁴ Gillies McIndoe Research Institute, Wellington 6021, New Zealand. Agadha.Wickremesekera@ccdhb.org.nz.
⁵ Department of Surgery, The University of Melbourne, Parkville, Victoria 3050, Australia. Agadha.Wickremesekera@ccdhb.org.nz.
⁶ Gillies McIndoe Research Institute, Wellington 6021, New Zealand. paul.davis@gmri.org.nz.
⁷ Department of Surgery, The University of Melbourne, Parkville, Victoria 3050, Australia. andrewk@hadassah.org.il.
⁸ Department of Neurosurgery, Hadassah Hebrew University Medical Centre, Jerusalem 91120, Israel. andrewk@hadassah.org.il.
⁹ Department of Surgery, The University of Melbourne, Parkville, Victoria 3050, Australia. theom@unimelb.edu.au.
¹⁰ Department of Surgery, The University of Melbourne, Parkville, Victoria 3050, Australia. Stanley.Stylli@mh.org.au.
¹¹ Department of Neurosurgery, The Royal Melbourne Hospital, Parkville, Victoria 3050, Australia. Stanley.Stylli@mh.org.au.
¹² Gillies McIndoe Research Institute, Wellington 6021, New Zealand. swee.tan@gmri.org.nz.
¹³ Department of Surgery, The University of Melbourne, Parkville, Victoria 3050, Australia. swee.tan@gmri.org.nz.
¹⁴ Wellington Regional Plastic, Maxillofacial & Burns Unit, Hutt Hospital, Lower Hutt 5040, New Zealand. swee.tan@gmri.org.nz.

Abstract

Patients with glioblastoma (GB), a highly aggressive brain tumor, have a median survival of 14.6 months following neurosurgical resection and adjuvant chemoradiotherapy. Quiescent GB cancer stem cells (CSCs) invariably cause local recurrence. These GB CSCs can be identified by embryonic stem cell markers, express components of the renin-angiotensin system (RAS) and are associated with circulating CSCs. Despite the presence of circulating CSCs, GB patients rarely develop distant metastasis outside the central nervous system. This paper reviews the current literature on GB growth inhibition in relation to CSCs, circulating CSCs, the RAS and the novel therapeutic approach by repurposing drugs that target the RAS to improve overall symptom-free survival and maintain quality of life.

Keywords: cancer stem cells; drug repurposing; glioblastoma; renin-angiotensin system.

Publication types

Review

MeSH terms

Angiotensin-Converting Enzyme Inhibitors / pharmacology
Brain Neoplasms / metabolism
Brain Neoplasms / pathology*
Cathepsin B / genetics
Cathepsin B / metabolism
Drug Repositioning
Epithelial-Mesenchymal Transition
Glioblastoma / metabolism
Glioblastoma / pathology*
Humans
Neoplasm Metastasis
Neoplastic Stem Cells / metabolism*
Renin-Angiotensin System* / drug effects

Substances

Angiotensin-Converting Enzyme Inhibitors
Cathepsin B