What Is Electrochemotherapy (ECT)?
Electrochemotherapy is a local tumour treatment based on rendering the cell membrane transiently permeable with electric pulses and delivering a cytotoxic drug into the cell within that window. The standard protocol is designed to produce mainly reversible permeabilisation: the cytotoxic effect comes principally from the drug, while the field gets the drug to its target. The same biophysics becomes directly ablative at higher field strengths, which is irreversible electroporation.
What Is Electroporation?
When electric pulses of sufficient strength and controlled duration are applied to a cell membrane, transiently permeable regions form in the lipid bilayer. This phenomenon is called electroporation. Once the field strength rises above the irreversible threshold, the permeability becomes permanent and the cell dies; the two thresholds are distinct.
These two regimes underpin two entirely different treatment strategies. In the reversible regime the aim is not to kill the cell but to let a cytotoxic drug that normally cannot cross the membrane enter it; this is electrochemotherapy. In the irreversible regime the electric field itself is the ablative agent and no drug is used.
The two agents most often used in electrochemotherapy are bleomycin and cisplatin. Bleomycin is a large hydrophilic molecule that crosses an intact membrane only with difficulty. Under electroporation the increase reported for bleomycin cytotoxicity ranges from several hundred to several thousand fold , , ; the reported factor varies with the measurement conditions and the cell system.
The subject of this portal is the reversible regime. Irreversible electroporation (IRE) is a different regime that ablates directly without a drug and appears in the corpus as comparative context; it is covered on its own page.
How Does Membrane Permeability Change?
What separates the reversible and irreversible regimes is the intensity of the same physical phenomenon
At rest the cell membrane carries a potential difference between its inside and outside. When an external electric field is applied, an additional induced transmembrane potential develops across the membrane. Once this potential exceeds a critical threshold, water-filled permeable structures appear in the lipid bilayer. The numerical value of that threshold depends on the tissue and the cell: in a model validated in vivo in rabbit liver the reversible threshold was estimated at 394 ± 75 mV and the irreversible threshold at 694 ± 136 mV , while a modelling study of breast cell lines computed the same quantity as 0.53 V to 1.31 V .
At field strengths just above the threshold these structures reseal within seconds to minutes after the pulse and the cell stays viable: reversible electroporation. As field strength and total energy rise, repair capacity is exceeded, homeostasis is permanently lost and the cell dies: irreversible electroporation. The boundary between the two regimes is not a sharp line but a transition zone that depends on tissue type and pulse parameters.
Rabbit liver, model validated in vivo
Breast cell lines, modelling study
Why Bleomycin and Cisplatin?
Both agents suit electrochemotherapy because they are strongly cytotoxic once inside the cell. No meaningful gain is expected from electroporation for drugs that already cross the membrane freely; this principle directly governs agent selection.
Bleomycin
A hydrophilic, relatively large molecule that cannot diffuse across an intact membrane and enters the cell only through a slow route that depends on a membrane protein. Once inside it produces single- and double-strand DNA breaks, and it is a very potent cytotoxic agent to the extent that it gets in , . Electroporation removes this access bottleneck: the reported increase in cytotoxicity is given as several hundred fold , as 300–700 fold and as 8,000 fold , , differing with the experimental setting.
Cisplatin
Crosses the membrane more readily than bleomycin, so the gain from electroporation is more modest. In the same comparisons the reported increase in cytotoxicity is roughly 80-fold for cisplatin against 8,000-fold for bleomycin , ; in human microvascular endothelial cells the same measures are about 10-fold and 5,000-fold . In the standard procedures cisplatin is given intratumourally, while bleomycin may be given either intravenously or intratumourally .
Bleomycin
300–700 fold
5,000 fold, human microvascular endothelial cells
8,000 fold ,
Cisplatin
about 10 fold, human microvascular endothelial cells
about 80 fold ,
Vascular Lock and Tissue-Level Effects
After the pulses a transient reduction in tissue blood flow is observed. Known in the literature as the vascular lock, it has been shown by in vivo imaging as constriction of the vessels, increased vessel permeability and reduced perfusion , . In murine sarcoma, tumour blood flow fell by about 70% immediately after the pulses and recovered within 24 hours .
Clinical series report bleeding control in bleeding superficial and mucosal lesions as a palliative benefit of electrochemotherapy , . Linking that observation to the vascular effects above is a mechanistic interpretation; the cause of the bleeding control has not been isolated in a controlled study.
The high sensitivity of vascular endothelial cells to a drug delivered with electroporation is one component of the observed antivascular effect . It has further been proposed that damage-associated molecular patterns released from dying tumour cells contribute to a systemic immune response; that idea is the starting point of the research line combining ECT with immune checkpoint inhibitors , .
Historical Milestones
- 1982Neumann et al. demonstrated DNA transfer into cells by electric pulses, establishing the molecular basis of electroporation. outside the corpus, no source record
- 1991Mir et al. reported that the antitumour effect of bleomycin can be potentiated by local electric pulses, the birth of electrochemotherapy.
- 1993Belehradek et al. published the first clinical phase I–II trial.
- 2006The ESOPE project defined standard operating procedures for cutaneous tumours and the Cliniporator system. ,
- 2010–2011Electrochemotherapy of deep-seated tumours began as a separate line of development: the first applications were reported with treatment planning and long variable-geometry needle electrodes. ,
- 2013–2014NICE issued interventional procedure guidance for cutaneous metastases (IPG446 in 2013, today HTG305) and primary basal/squamous cell carcinoma (IPG478 in 2014, today HTG333). NICE HTG305 NICE HTG333
- 2018The ESOPE standard operating procedures were updated. The update covers cutaneous tumours and skin metastases; internal organ tumours are left outside its scope.
- 2010s–presentCalcium electroporation, gene electrotransfer and immunotherapy combinations entered clinical trials. , ,
Which Literature Is This Page Based On?
The account above is an editorial synthesis based on the 968 publications in the General Principles & Biophysics area of the oncology corpus. Every numerical statement on this page carries its source beside it; clicking a source opens the citation and abstract drawer.
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