Research
We are developing a novel method for treating advanced carcinomas that we call targeted osmotic lysis, or TOL. Carcinomas over-express voltage sodium channels by 10- to 20-fold. Others have blocked these channels to slow metastasis and invasiveness. Instead, we activate the channels with a pulsed electric field while simultaneously blocking the sodium pumps that return the sodium to the extracellular space with a cardiac glycoside drug. This results in a very high intracellular sodium concentration. Because water follows sodium, the cancer cells swell and lyse. Normal cells with fewer sodium channels and less intracellular sodium do not lyse. We have evidence that this will work in breast, lung, prostate, pancreatic, mast cell, colon, orofacial, and cervical cancers. We are currently working on translational studies to increase efficacy and progress towards clinical trials.
Recent Publications
Gould, H., Norleans, J., Ward T.J., Reid, C. and Paul, D. (2018) Selective Lysis of Breast Carcinomas by Simultaneous Stimulation of Sodium Channels and Blockade of Sodium Pumps. Oncotarget 9: 15606-15615.
Paul, D., Maggi, P., del Piero, F., Scahill, S.D., Sherman, K.J., Edenfield, S., and Gould, H.J., III (2020) Targeted osmotic lysis of highly invasive breast carcinomas using a pulsed magnetic field and pharmacological blockade of voltage-gated sodium channels. Cancers 12: 1420, doi: 10.3390/cancers12061420.
Bazan, H.A., Bhattacharjee, S., Burgos, C., Recio, J., Abet, V,., Pahng, A.R., Bokkyoo, J., Heap, J., Ledet, A.J., Gordon, W.C., Edwards, S., Paul, D., Alvarez-Builla, J., Bazan, N.G. (2020) A novel pipeline of 2-(benzenesulfonamide)-N-(4-hydroxyphenyl) acetamide analgesics that lack hepatotoxicity and retain antipyresis. Eur. J. Med. Chem. DOI: 10.1016/j.ejmech.2020.112600
Gould, H.J. III, Miller, P.R., Edenfield, S.I., Sherman, K.J., Brady, C.K., and Paul, D. (2021) Emergency use of targeted osmotic lysis for the treatment of a patient with aggressive, late-stage squamous cell carcinoma of the cervix. Curr Oncol. 28:2115-2122. doi: 10.3390/curroncol28030196.
Gould, H.J. and Paul, P. (2022) Targeted Osmotic Lysis: A Novel Approach to Targeted Cancer Therapies. Biomedicines:10, 838. https://doi.org/10.3390/biomedicines10040838
Gould, H.J. III, Edenfield S.I., Miller, P.R., Sherman, K.J., Melius, B., Whitney, A., Hunter, R.P., Del Piero, F., Tracey, D. and Paul, D. (2022) The role of targeted osmotic lysis in the treatment of advanced carcinoma in companion animals: A case series. Case Rep Vet Med. 2022:2747108 doi: 10.1155/2022/2747108
Gould, H.J. III, and Paul, D. (2022) Cancer as a Channelopathy—Appreciation of Complimentary Pathways Provides a Different Perspective for Developing Treatments. Cancers 14:4627. doi:10.3390/cancers14194627
Edenfield, S., Sims, A.M., Porretta, C., Gould, H.J., Paul, D. (2022) Effect of Cell Cycle on Cell Surface Expression of Voltage- Gated Sodium Channels and Na+,K+-ATPase. Cells