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The Renin–Angiotensin System in the Tumor Microenvironment of Glioblastoma

1
Department of Neurosurgery, Wellington Regional Hospital, Wellington 6021, New Zealand
2
Gillies McIndoe Research Institute, Wellington 6021, New Zealand
3
Department of Surgery, The Royal Melbourne Hospital, The University of Melbourne, Parkville, VIC 3050, Australia
4
Department of Neurosurgery, Hadassah Hebrew University Medical Centre, Jerusalem 91120, Israel
5
Wellington Regional Plastic, Maxillofacial & Burns Unit, Hutt Hospital, Lower Hutt 5040, New Zealand
*
Authors to whom correspondence should be addressed.
Equal first authors.
Academic Editor: Sheila K. Singh
Cancers 2021, 13(16), 4004; https://doi.org/10.3390/cancers13164004
Received: 17 July 2021 / Revised: 3 August 2021 / Accepted: 6 August 2021 / Published: 9 August 2021
(This article belongs to the Special Issue Novel Treatment Strategies for Glioblastoma)
Glioblastoma (GB) is the most aggressive brain cancer in humans. Patient survival outcomes have remained dismal despite intensive research over the past 50 years, with a median overall survival of only 14.6 months. We highlight the critical role of the renin–angiotensin system (RAS) on GB cancer stem cells and the tumor microenvironment which, in turn, influences cancer stem cells in driving tumorigenesis and treatment resistance. We present recent developments and underscore the need for further research into the GB tumor microenvironment. We discuss the novel therapeutic targeting of the RAS using existing commonly available medications and utilizing model systems to further this critical investigation.
Glioblastoma (GB) is an aggressive primary brain tumor. Despite intensive research over the past 50 years, little advance has been made to improve the poor outcome, with an overall median survival of 14.6 months following standard treatment. Local recurrence is inevitable due to the quiescent cancer stem cells (CSCs) in GB that co-express stemness-associated markers and components of the renin–angiotensin system (RAS). The dynamic and heterogeneous tumor microenvironment (TME) plays a fundamental role in tumor development, progression, invasiveness, and therapy resistance. There is increasing evidence showing the critical role of the RAS in the TME influencing CSCs via its upstream and downstream pathways. Drugs that alter the hallmarks of cancer by modulating the RAS present a potential new therapeutic alternative or adjunct to conventional treatment of GB. Cerebral and GB organoids may offer a cost-effective method for evaluating the efficacy of RAS-modulating drugs on GB. We review the nexus between the GB TME, CSC niche, and the RAS, and propose re-purposed RAS-modulating drugs as a potential therapeutic alternative or adjunct to current standard therapy for GB. View Full-Text
Keywords: glioblastoma; renin–angiotensin system; pluripotent stem cells; organoids; cancer stem cells; cancer stem cell niche; tumor microenvironment glioblastoma; renin–angiotensin system; pluripotent stem cells; organoids; cancer stem cells; cancer stem cell niche; tumor microenvironment
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MDPI and ACS Style

O’Rawe, M.; Kilmister, E.J.; Mantamadiotis, T.; Kaye, A.H.; Tan, S.T.; Wickremesekera, A.C. The Renin–Angiotensin System in the Tumor Microenvironment of Glioblastoma. Cancers 2021, 13, 4004. https://doi.org/10.3390/cancers13164004

AMA Style

O’Rawe M, Kilmister EJ, Mantamadiotis T, Kaye AH, Tan ST, Wickremesekera AC. The Renin–Angiotensin System in the Tumor Microenvironment of Glioblastoma. Cancers. 2021; 13(16):4004. https://doi.org/10.3390/cancers13164004

Chicago/Turabian Style

O’Rawe, Michael, Ethan J. Kilmister, Theo Mantamadiotis, Andrew H. Kaye, Swee T. Tan, and Agadha C. Wickremesekera 2021. "The Renin–Angiotensin System in the Tumor Microenvironment of Glioblastoma" Cancers 13, no. 16: 4004. https://doi.org/10.3390/cancers13164004

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