Is there a role for voltage-gated Na+ channels in the aggressiveness of breast cancer?

Abstract

Breast cancer is the most common cancer among women and its metastatic potential is responsible for numerous deaths. Thus, the need to find new targets for improving treatment, and even finding the cure, becomes increasingly greater. Ion channels are known to participate in several physiological functions, such as muscle contraction, cell volume regulation, immune response and cell proliferation. In breast cancer, different types of ion channels have been associated with tumorigenesis. Recently, voltage-gated Na+ channels (VGSC) have been implicated in the processes that lead to increased tumor aggressiveness. To explain this relationship, different theories, associated with pH changes, gene expression and intracellular Ca2+, have been proposed in an attempt to better understand the role of these ion channels in breast cancer. However, these theories are having difficulty being accepted because most of the findings are contrary to the present scientific knowledge. Several studies have shown that VGSC are related to different types of cancer, making them a promising pharmacological target against this debilitating disease. Molecular biology and cell electrophysiology have been used to look for new forms of treatment aiming to reduce aggressiveness and the disease progress.

Breast cancer therapy affects the expression of antineonatal Nav1.5 antibodies in the serum of patients with breast cancer

“…The metastatic potential of breast cancer cells increases with the degree of cell aggressiveness ( 32 ). Cells that originate from metastatic tumors are known to have unique genetic alterations to maintain their malignant characteristics, such as the ability to invade and metastasize ( 32 ). These genetic alterations may lead to the development of unique markers or antigens that contribute to the progression of metastases ( 32 ).…”

“…Cells that originate from metastatic tumors are known to have unique genetic alterations to maintain their malignant characteristics, such as the ability to invade and metastasize ( 32 ). These genetic alterations may lead to the development of unique markers or antigens that contribute to the progression of metastases ( 32 ). The involvement of VGSCs was attributed to the metastatic capacity of breast cancer cells ( 23 ).…”

Somatic Mutations Profile of a Young Patient With Metastatic Urothelial Carcinoma Reveals Mutations in Genes Involved in Ion Channels

“…Thus, a growing body of research demonstrates that ion channels could be potential therapeutic targets for UC. Currently, the large availability of pharmacological agents targeting the majority of ion channels: amlodipine and cilnidipine, calcium channel blockers in breast cancer (26); Iberiotoxin, charybdotoxin and clotrimazole, potassium channel blockers in breast and cervical cancers (31); tetrodotoxin, voltage gated sodium channels blocker in breast cancer (32) and others, offer a broad therapeutic avenue for anticancer therapy.…”

Scorpion Toxins and Ion Channels: Potential Applications in Cancer Therapy

“…Pharmacological blockage or upregulation of VGSCs may treat certain types of cancer, especially cases in which Na + channels regulate malignancy [39]. Due to the positive correlation between Na + channel expression and cancer invasion, Na + channel blockers may represent promising new therapies [96][97][98].…”