Electrical voltage patterns in healthy cells serve as a guide for a well-organized cell development process. The opposite occurs with cancer, though. Cells lose their specialized roles, start growing into tumors, and spread into other tissues—a process known as metastasis. This process also causes a breakdown in the cell’s normal electrical patterns. Metastasis continues to be the biggest cause of death in cancer patients, and drugs that modulate the electrical patterns of tumor cells may hold promise as novel treatments.
Researchers at Tufts University recently demonstrated that tumor cell invasion in vitro and metastasis in animal models of breast cancer can both be reduced considerably by altering the voltage patterns in tumor cells using ion channel blocking drugs that have already received FDA approval for the treatment of other illnesses.
An accelerated path to approval for the treatment of cancer may result from the revelation that medications, currently approved for other illnesses, can halt or stop spreading. A large selection of ready-to-use medications could be used for cancer therapy because ion channels, which control the bioelectrical properties of cells, are the third-most frequent targets for current pharmaceuticals.
Triple-negative breast cancer (TNBC), which makes up around 15% of all occurrences of breast cancer, was the focus of a recent Tufts University study. TNBC has a higher likelihood of spreading than any other subtype of breast cancer, thus researchers are concentrating their efforts on treating it because it has a dismal five-year prognosis. The Tufts team was able to demonstrate that modulating the membrane voltage properties of breast cancer cells can affect the progression of metastasis. Using a mouse lung model, they showed a decrease of 50% in the number of metastatic sites.
A wide range of ion channel-target drugs already exist, which affect the ability of cells to conduct positively or negatively charged ions across the cellular membrane. These drugs are used to treat anxiety, pain, metabolism, and cardiovascular disorders.
In the study, Tufts scientists genetically over-expressed potassium ion channels in tumor cells, which caused the inside of the cells to become more negatively charged. As a result of the voltage imbalance, tumor growth and metastasis in plated cells and animal models were both accelerated. In contrast, blocking the ion channels resulted in a restoration of normal cell voltages, decreased tumor cell invasion, and a markedly reduced rate of metastasis.
Their findings were published in the eBioMedicine:
Potassium channel-driven bioelectric signalling regulates metastasis in triple-negative breast cancer
The efficiency of four FDA-approved potassium ion channel blockers in eliminating tumor cells was compared in the study. Amiodarone, which had the greatest impact on restoring normal cell voltages, was chosen to be tested for its efficacy in treating breast cancer in mice. The medicine, which is authorized for use in treating cardiac rhythm abnormalities, was found to reduce the tumor’s capacity to spread as cells detached and traveled to different places of the body.
The researchers discovered a number of biochemical pathways involved in cell migration by examining the genes that were activated by the voltage shift. The ion channel-blocking drug’s actions were consistent with restricting the mobility of the cells, preventing them from straying and developing new tumors.
In addition to current standard-of-care therapies like chemotherapy, the Tufts team will continue to investigate the impact of ion channel blockers on cancer in animal models. Since amiodarone and comparable medications have already received human use approval, Phase I clinical trials in small groups of cancer patients may begin soon.
More and more studies are confirming the importance of ion channel modulation in cancer treatment and therapy. Although traditionally used for cardiac and neurological research, dedicated ion channel research devices such as Fluxion’s IonFlux Mercury automated patch clamp systems are perfectly suited for potassium channel modulation for cancer research.
Ali Yehia has a Ph.D. in Cardiac Electrophysiology from McGill University. He has been involved in ion channel screening using Automate Patch Clamp since 2006. He joined Fluxion Biosciences in 2012, where he developed ion channel assays and IonFlux Mercury systems. He was the Chief Scientific Officer at Fluxion before moving to Cell Microsystems as the new Senior Director of the IonFlux product.
