Novel insights into voltage-gated ion channels: Translational breakthroughs in medical oncology

ABSTRACT

Preclinical evidence suggests that voltage gradients can act as a kind of top-down master regulator during embryogenesis and orchestrate downstream molecular-genetic pathways during organ regeneration or repair. Moreover, electrical stimulation shifts response to injury toward regeneration instead of healing or scarring. Cancer and embryogenesis not only share common phenotypical features but also commonly upregulated molecular pathways. Voltage-gated ion channel activity is directly or indirectly linked to the pathogenesis of cancer hallmarks, while experimental and clinical studies suggest that their modulation, e.g., by anesthetic agents, may exert antitumor effects. A large recent clinical trial served as a proof-of-principle for the benefit of preoperative use of topical sodium channel blockade as a potential anticancer strategy against early human breast cancers. Regardless of whether ion channel aberrations are primary or secondary cancer drivers, understanding the functional consequences of these events may guide us toward the development of novel therapeutic approaches.

KEYWORDS:

• Ion
• channels
• regeneration
• cancer
• treatment
• translational research

Highlights

• Cancer and embryogenesis not only share common phenotypical features but also commonly upregulated molecular pathways.

• Elegant experiments showed that bioelectrical signals act as a top-down master regulator during embryogenesis, while electrical signals shift response to injury toward regeneration instead of healing or scarring.

• Voltage-gated ion channel activity is directly or indirectly linked to the pathogenesis of all cancer hallmarks, while experimental and clinical studies suggest that their modulation may exert antitumor effects.

• A large recent clinical study showed that preoperative administration of local anesthetics in patients with early breast cancer can improve survival.

• The efforts to understand and therapeutically exploit bioelectric signals in cancer should intensify.

Disclosure statement

All authors report no financial or non-financial conflicts of interests.

Data availability statement

Data sharing is not applicable to this article because no new data was created or analyzed in this study.

Additional information

Funding

This paper was not funded.