Tkachenko S. S., Rodynskyi O. H., Portniaha M. M.

NAV1.5: ATYPICAL FUNCTIONS OF VOLTAGE-GATED SODIUM CHANNELS IN TUMOR CELLS AND NEW PERSPECTIVES IN THE TREATMENT OF BREAST CANCER

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Tkachenko S. S., Rodynskyi O. H., Portniaha M. M.

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LITERATURE REVIEWS

Type of article:

Scientific article

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Breast cancer, characterized by unique epidemiological features and significant heterogeneity, is the leading cause of cancer death in women. Conventional treatments are associated with significant side effects. The aim of this work was to systematize the data of scientific publications devoted to the physiological function of the voltage-gated sodium channel Nav1.5 in normal and tumor processes, to summarize the results of studies of its selective inhibition in breast cancer. Nav1.5 and nNav1.5 are expressed in breast cancer cells, generate a stable sodium current, alter the kinetics of activation and inactivation, and increase extracellular acidification, promoting invasive growth and metastasis. nNav1.5 is more resistant to low pH. Nav1.5 participates in the formation of complexes with β1-integrin, K⁺-channel hERG1 and Na⁺/H⁺-antiporter NHE1, which regulate relevant cancer processes in the breast. It has been shown that blocking Nav1.5 with non-selective inhibitors (lidocaine and ranolazine) suppresses the pathological late Nav1.5 current, and selective inhibitors or antibodies reduce cell invasion and tumor volume in in vitro and in vivo models. Expression of Nav1.5 (nNav1.5 isoform) in breast cancer cells promotes invasion, metastasis and tumor growth. Blockade of nNav1.5 reduces invasive potential and tumor mass in preclinical models, while non-specific inhibitors affect cell motility, metabolism and interaction with the extracellular matrix; clinical trials of Nav1.5 blockers for 2025 are in the early stages, demonstrating the potential as targeted therapy.

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Bibliography:

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Publication of the article:

«Bulletin of problems biology and medicine», 2025 Issue 4, 179, 80-85 pages, index UDC 612.83:612.662.9:618.173-073.7/-076-085:615.2.1-092.9

DOI:

10.29254/2077-4214-2025-4-179-80-85