Upregulation of voltage-gated sodium channels (VGSCs) and Na+/K+-ATPase (sodium pumps) is common across most malignant carcinomas. Targeted osmotic lysis (TOL) is a developing technology in which the concomitant stimulation of VGSCs and pharmacological blockade of sodium pumps causes rapid selective osmotic lysis of carcinoma cells. This treatment of cervical carcinoma is evidence that TOL is a safe, well-tolerated and effective treatment for aggressive advanced carcinomas that has the potential to extend life without compromising its quality. TOL is likely to have broad application for the treatment of advanced-stage carcinomas.
Background. Targeted osmotic lysis (TOL) is a novel technology that involves concomitant stimulation of voltage-gated sodium channels (VGSCs) and the pharmacological blockade of Na+, K+-ATPase causing lysis of highly malignant cancer cells. Hypothesis/Objectives. TOL offers an option for treating advanced carcinomas in companion animals. Animals. Two cats and 2 dogs that presented to veterinary hospitals for evaluation and treatment of one of several forms of carcinoma. Methods. Digoxin was administered to achieve steady-state, therapeutic concentrations. The animals were then exposed to pulsed electric field stimulation. Pre- and posttreatment assessments of tumor size and quality of life were compared. The treatment frequency and survivability varied, based on the patient’s premorbid functioning and response to treatment. Results. Regardless of cancer type, TOL consistently increased survival beyond expected, often improving, but without compromising of quality of life. Conclusions and Clinical Importance. TOL warrants consideration as an option for managing advanced carcinomas.
Targeted osmotic lysis (TOL) is a novel technology that involves the concomitant stimulation of voltage‐gated sodium channels (VGSCs) and pharmacological blockade of Na+, K+‐ATPase (sodium pumps) causing selective osmotic lysis of highly malignant cancer cells that may offer an option for treating advanced carcinomas in companion animals. We hypothesized, that as in experimental animals, TOL would be able to increase survival beyond that anticipated for animals with advance carcinoma without adversely affecting quality of life. Accordingly, we treated 2 feline and 3 canine companion animals in which TOL was used to safely treat advanced carcinoma. Based on available pre‐clinical evidence for safety, efficacy and lack of off‐target damage to normal tissue, companion animals diagnosed with advanced carcinomas that were experiencing impaired behavior and functionality were offered trial treatment with TOL. When practical, biopsy samples were obtained to determine the level of VGSC expression. Digoxin was administered to achieve steady‐state, therapeutic tissue levels. The animals were then exposed to pulsed electric field stimulation. Post‐treatment measurements of tumor size and assessments of behavior and functionality were compared to pre‐treatment observations made by the owners and by the treating veterinarian. The frequency of treatments and survival varied, based on the patient’s level of pre‐morbid functioning and response to treatment. In all five cases, TOL the animals survived beyond the prognosis. In 3 cases, owners reported behavioral improvement. The results support the hypothesis that TOL may provide a therapeutic option with broad application in veterinary practice as a safe, well‐tolerated and effective option for treating patients with advanced stage carcinoma.
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