The biological target
Voltage-gated sodium channels (VGSCs) are membrane proteins that regulate sodium ion flow across the cell membrane. In normal tissue, VGSCs are expressed at modest density and their activity is tightly coupled to sodium-potassium ATPase pumps that move sodium back out of the cell.
Advanced-stage solid tumor cells over-express VGSCs at approximately 10 to 50 times the density seen in normal tissue. The differential is consistent across many carcinoma types, including breast, prostate, colorectal, lung, ovarian, pancreatic, gastric, esophageal, and melanoma. The mechanism is reviewed in detail at /literature.
The over-expression is the target. The procedure exploits the density differential to selectively damage cells that present the target while leaving normal cells intact.
Component one. The drug.
The drug component is a cardiac glycoside. Cardiac glycosides act as sodium pump (Na+/K+ ATPase) inhibitors. When the sodium pump is blocked, the cell loses the ability to expel sodium it has taken in.
Why a generic cardiac drug
Digoxin has a sixty-plus year clinical history in humans, a defined therapeutic range, a well-characterized pharmacokinetic profile, and broad availability as a generic. The choice is intentional. Repurposing an approved drug at its established cardiac dose lowers the regulatory complexity of the combined therapy compared with developing a novel small molecule.
Other cardiac glycosides with potentially more selective sodium pump inhibition are under research consideration but are not currently FDA-approved for human use. Digoxin is the working component today.
Component two. The device.
The device component is a coaxial ring electric field generator. The device produces a pulsed electric field across the treatment chamber. The pulse pattern is engineered to open voltage-gated sodium channels at the cell membrane, allowing rapid sodium influx into cells expressing the channel.
Two device sizes have been built. The smaller chamber is used in veterinary and preclinical work. The larger chamber accommodates a human patient. Both devices generate the same pulse profile across the treatment volume.
The mechanism, in sequence
The two components act in sequence. Neither component alone reproduces the effect.
Drug loads the patient
The cardiac glycoside is given orally for a loading period before treatment. The drug binds the sodium pump and inhibits sodium efflux. Cells lose the ability to expel accumulated sodium during the treatment window.
Pulsed electric field opens VGSCs
The patient enters the chamber. The device generates the engineered pulse pattern. Voltage-gated sodium channels open across the body. Sodium enters cells in proportion to the channel density at the membrane.
Differential sodium accumulation
Normal cells, with low VGSC density, accumulate modest sodium. The cell tolerates the load and recovers when the pulse stops. Cancer cells, with VGSCs over-expressed at 10 to 50 times normal density, accumulate sodium at the same multiple.
Osmotic lysis of cancer cells
Water follows sodium. The cancer cell volume increases beyond what the membrane can contain. The cell ruptures. Adjacent normal cells, having accumulated only modest sodium, return to baseline when the drug wears off.
Treatment recovery
The patient leaves the chamber. The cardiac glycoside clears on its standard pharmacokinetic profile. Sodium balance returns to baseline in surviving cells.
The mechanism is non-thermal. There is no ablation, no cutting, no chemo-cytotoxic damage to dividing normal cells, and no ionizing radiation.
Patient eligibility screen
Because the mechanism depends on VGSC over-expression, eligibility is determined by a per-patient tumor screen, not by stage or by primary site alone.
Required screen
- Tumor biopsy. Recent tissue, preferably less than 90 days old. Slides and block must be available for the screening laboratory.
- VGSC immunohistochemistry assay. The screening assay quantifies sodium channel density in the patient's tumor relative to a normal-tissue control. A patient whose tumor over-expresses VGSCs at the threshold is a candidate.
- Imaging baseline. CT, MRI, or PET as appropriate to the tumor type, dated within the prior 60 days.
- Treatment history. Full record of prior therapy, current medications, and performance status.
- Renal function panel. Required because digoxin is renally cleared.
Standard exclusions
- Hematologic malignancies and bone marrow primary cancers
- Pre-existing cardiac arrhythmia incompatible with digoxin therapy
- Severe renal impairment
- Tumors not demonstrating VGSC over-expression on the screening assay
The treatment protocol
A representative treatment cycle, drawn from the protocol currently in use in veterinary practice and adapted as the human protocol matures. Specific session durations, drug doses, and follow-up intervals are per-patient and per-protocol.
Pre-treatment
Drug loading begins approximately six days before the first session. The patient remains at home during the loading window. No facility stay is required. Lab monitoring confirms the drug is within therapeutic range before the first session.
Session one
The patient enters the chamber. A treatment session is on the order of two hours, with one rest break at the midpoint. No sedation is required. No surgical preparation. Patients remain awake and conversational throughout.
Session two
A second session is performed the following day under the same protocol. Two sessions complete one treatment cycle.
Post-treatment assay
Post-treatment biopsy and follow-up imaging are scheduled per the protocol. The clinical team compares pre- and post-treatment tumor density and reviews patient symptoms.
Cycle interval
Additional treatment cycles are scheduled at two to three week intervals depending on tumor response, the clinician's judgment, and the patient's tolerance.
What TOL is not
- Not surgery. No cutting, no resection.
- Not chemotherapy. No DNA-damaging agent. No cytotoxic effect on normal dividing tissue.
- Not radiation. No ionizing beam. No radiation dose record.
- Not thermal ablation. The device generates no heat.
- Not photodynamic therapy. No photosensitizer. No external light.
- Not immunotherapy. The mechanism does not depend on the patient's immune response to the tumor.
Adverse-effect profiles associated with chemotherapy, radiation, and surgical resection are not expected on first principles because none of those mechanisms is invoked. Adverse effects associated with cardiac glycoside dosing (most commonly nausea, visual disturbance, arrhythmia) are managed by the treating clinician.
Where the procedure is delivered
Today, the procedure is delivered at international partner sites operating under their local regulatory framework. The named Mexico partner facility is CORE Medical in Tijuana. Australian access runs through the Therapeutic Goods Administration Special Access Scheme. United States access is limited to authorized clinical trials, expanded access programs, and Right to Try Act eligibility.
Patient-facing intake, jurisdiction selection, financial pathways, and partner clinic introductions are coordinated through the sister site at FixCancers.com.
Read the underlying science
Every peer-reviewed paper on TOL, the LSU foundational patent, the mechanism papers, the preclinical work, the human emergency-use case report, and the published veterinary safety study are catalogued at /literature.