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Review
. 2025 Aug 6;26(15):7595.
doi: 10.3390/ijms26157595.

Deciphering the Role of Functional Ion Channels in Cancer Stem Cells (CSCs) and Their Therapeutic Implications

Krishna Samanta  1 , Gali Sri Venkata Sai Rishma Reddy  2 , Neeraj Kumar Sharma  3 , Pulak Kar  2
Affiliations
Review

Deciphering the Role of Functional Ion Channels in Cancer Stem Cells (CSCs) and Their Therapeutic Implications

Krishna Samanta et al. Int J Mol Sci. .

Abstract

Despite advances in medicine, cancer remains one of the foremost global health concerns. Conventional treatments like surgery, radiotherapy, and chemotherapy have advanced with the emergence of targeted and immunotherapy approaches. However, therapeutic resistance and relapse remain major barriers to long-term success in cancer treatment, often driven by cancer stem cells (CSCs). These rare, resilient cells can survive therapy and drive tumour regrowth, urging deeper investigation into the mechanisms underlying their persistence. CSCs express ion channels typical of excitable tissues, which, beyond electrophysiology, critically regulate CSC fate. However, the underlying regulatory mechanisms of these channels in CSCs remain largely unexplored and poorly understood. Nevertheless, the therapeutic potential of targeting CSC ion channels is immense, as it offers a powerful strategy to disrupt vital signalling pathways involved in numerous pathological conditions. In this review, we explore the diverse repertoire of ion channels expressed in CSCs and highlight recent mechanistic insights into how these channels modulate CSC behaviours, dynamics, and functions. We present a concise overview of ion channel-mediated CSC regulation, emphasizing their potential as novel diagnostic markers and therapeutic targets, and identifying key areas for future research.

Keywords: cancer stem cell; cancer therapeutics; cellular signalling; ion channel-targeted therapy; ion channels; tumour microenvironment.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Key ion channels and their roles in regulating cancer stem cell (CSC) stemness and survival.
Figure 2
Figure 2
Ion channels in cancer stem cells (CSCs) across various cancer types.
Figure 3
Figure 3
Targeting ion channels in cancer stem cells (CSCs) as a promising therapeutic strategy.
See this image and copyright information in PMC

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