Potassium Ion Channels in Malignant Central Nervous System Cancers

Yasmin Boyle; Terrance G Johns; Emily V Fletcher

doi:10.3390/cancers14194767

Potassium Ion Channels in Malignant Central Nervous System Cancers

Cancers (Basel). 2022 Sep 29;14(19):4767. doi: 10.3390/cancers14194767.

Authors

Yasmin Boyle^{1

2}, Terrance G Johns^{1

2}, Emily V Fletcher^{1

2}

Affiliations

¹ Telethon Kids Institute, Perth Children's Hospital, 15 Hospital Ave, Nedlands, Perth, WA 6009, Australia.
² School of Biomedicine, The University of Western Australia, 35 Stirling Hwy, Crawley, Perth, WA 6009, Australia.

Abstract

Malignant central nervous system (CNS) cancers are among the most difficult to treat, with low rates of survival and a high likelihood of recurrence. This is primarily due to their location within the CNS, hindering adequate drug delivery and tumour access via surgery. Furthermore, CNS cancer cells are highly plastic, an adaptive property that enables them to bypass targeted treatment strategies and develop drug resistance. Potassium ion channels have long been implicated in the progression of many cancers due to their integral role in several hallmarks of the disease. Here, we will explore this relationship further, with a focus on malignant CNS cancers, including high-grade glioma (HGG). HGG is the most lethal form of primary brain tumour in adults, with the majority of patient mortality attributed to drug-resistant secondary tumours. Hence, targeting proteins that are integral to cellular plasticity could reduce tumour recurrence, improving survival. This review summarises the role of potassium ion channels in malignant CNS cancers, specifically how they contribute to proliferation, invasion, metastasis, angiogenesis, and plasticity. We will also explore how specific modulation of these proteins may provide a novel way to overcome drug resistance and improve patient outcomes.

Keywords: cellular plasticity; glioblastoma; high grade glioma; medulloblastoma; potassium ion channels.

Publication types

Review

Grants and funding

The research work related to the review in the author’s lab is funded by multiple sources. This includes direct funding from Telethon Kids Institute and philanthropic donations made by the Ethan Davies Fellowship and The Robert Connor Dawes Foundation. Funding is also provided by grants from The Cure Starts Now, The Brain Tumour Charity, grant number GN-000546 and The Perth Children’s Hospital Foundation, grant number 9896. At the time of writing, the first author of this review was receiving the support of the Australian Government Research Training Program Scholarship at The University of Western Australia.