Exploring Neonatal NaV1.5 Voltage-Gated Sodium Channel as a Therapeutic Target in Cancer
10.31436/ imjm.v25i01.2984
- Author:
Mohd Redhuan Mohd Noor
1
;
Siti Yusrina Nadihah Jamaludin
2
;
Mohd Harizal Senik
3
;
Farizan Ahmad
3
;
Noor Fatmawati Mokhtar
4
;
Izuddin Fahmy Abu
5
;
Muhammad Yusran Abdul Aziz
6
Author Information
1. Faculty of Medicine, Universiti Sultan Zainal Abidin, Medical Campus, Jalan Sultan Mahmud, Terengganu, Malaysia;Environment Technology, Faculty of Ocean Engineering Technology, Universiti Malaysia Terengganu, Terengganu, Malaysia
2. Faculty of Medicine, Universiti Sultan Zainal Abidin, Medical Campus, Jalan Sultan Mahmud, Terengganu, Malaysia
3. Department of Neurosciences, School of Medical Sciences, Health Campus, Universiti Sains Malaysia, Kelantan, Malaysia
4. Institute for Research in Molecular Medicine (INFORMM), USM Health Campus, Kelantan, Malaysia
5. Universiti Kuala Lumpur, Institute of Medical Science Technology, Selangor, Malaysia
6. UniSZA Science and Medicine Foundation Centre (PUSPA), Universiti Sultan Zainal Abidin, Terengganu, Malaysia
- Publication Type:Review
- Keywords:
Voltage-gated sodium channel;
neonatal NaV1.5;
metastasis;
targeted therapy;
biomarker.
- From:
The International Medical Journal Malaysia
2026;25(No. 1):30-40
- CountryMalaysia
- Language:English
-
Abstract:
Voltage-gated sodium channels (VGSCs) play pivotal roles in cancer progression and
have emerged as promising therapeutic targets and biomarkers. VGSCs comprise
multiple subtypes with distinct tissue distributions, influencing tumour characteristics in
different ways. Among these, the tetrodotoxin-sensitive α-subunits and the β1 subunit,
commonly found in breast cancer, have been implicated in metastasis and tumour
aggressiveness. The NaV1.5 channel and its neonatal variant (nNaV1.5) are
overexpressed in aggressive cancers such as breast, prostate, colorectal, and lung cancers,
thereby enhancing their invasive capacity. nNaV1.5 is particularly significant due to its
tumour-specific expression and strong association with poor prognosis, especially
in breast cancer, where it regulates cell proliferation, invasion, and tumour
microenvironment remodelling. This review highlights nNaV1.5 as a critical ion channel
that drives metastasis through ion regulation, extracellular acidification, and cytoskeletal
remodelling. We further evaluate current therapeutic strategies, including siRNA,
monoclonal antibodies, and small-molecule inhibitors, while addressing translational
challenges such as tumour heterogeneity, drug delivery limitations, and off-target
cardiotoxicity due to its similarity with the adult isoform. In addition, we explore the
potential of nNaV1.5 as a biomarker subject to epigenetic regulations by factors
including RE1-silencing transcription factor (REST) and histone deacetylase 2 (HDAC2),
which may facilitate patient stratification and treatment optimization. By integrating
mechanistic insights, therapeutic opportunities, and translational challenges, this review
goes beyond descriptive summaries to provide a framework for advancing nNaV1.5
research from preclinical studies toward clinical application in cancer therapy.
- Full text:2026060310533144786RA+2984.pdf
