| Rank |
Pathway / Axis |
Cancer Cells (↑ / ↓ / ↔) |
Normal Cells (↑ / ↓ / ↔) |
TSF |
Primary Effect |
Notes / Interpretation |
| 1 |
Membrane electroporation (Reversible vs Irreversible) |
↑ permeabilization / disruption |
↑ permeabilization / disruption |
P |
Immediate loss of membrane barrier |
Category mapping: Reversible EP → ECT / Ca-EP; Irreversible EP → IRE. Selectivity is largely geometric (field distribution) and cellular (repair capacity), not “cancer-only”. |
| 2 |
ECT drug uptake (bleomycin/cisplatin) / intracellular access |
↑ intracellular drug delivery |
↑ intracellular drug delivery |
P→R |
Local chemosensitization |
Category: ECT is a delivery amplifier; efficacy depends on timing + local perfusion. Often enables potent effect from otherwise poorly permeant agents. |
| 3 |
Ca2+ axis (influx, overload, ER–mitochondria coupling) |
↑ Ca2+ dysregulation |
↑ Ca2+ dysregulation |
P→R |
Mitochondrial stress, apoptosis/necrosis spectrum |
Pulse width and repetition strongly shape outcome; Ca electroporation leverages Ca2+-driven bioenergetic collapse as a drug-free approach. |
| 4 |
Mitochondria / MPTP + bioenergetic collapse |
↑ depolarization / ATP loss |
↑ depolarization / ATP loss |
R |
Cell death execution + metabolic failure |
Often downstream of Ca2+ overload + membrane failure; nsPEF is frequently framed as more “intracellular/organellar” stress-forward than classic µs EP. |
| 5 |
ROS (oxidative burst → signaling) |
↑ (context-dependent) |
↑ (context-dependent) |
R→G |
Stress signaling, damage amplification |
ROS can be secondary to Ca2+/mitochondria and/or electrochemical effects at electrodes. Direction and magnitude depend on pulse protocol, conductivity, and oxygenation. |
| 6 |
NRF2 antioxidant response / adaptation |
↑ (context-dependent; resistance role) |
↑ (protective role) |
G |
Redox adaptation |
NRF2 upshifts can protect normal tissue but may also support tumor survival post-sublethal EP (repair/tolerance). Relevance rises when aiming for non-ablative or fractionated protocols. |
| 7 |
Vascular axis (perfusion, endothelial effects) |
↓ perfusion (often) / local ischemia |
↓ perfusion (local) |
R |
Secondary tumor control via antivascular effects |
Prominent in ECT literature (composite antivascular + cytotoxic). In IRE, ECM sparing may preserve larger structures while still affecting microvasculature. |
| 8 |
Immunogenic cell death / DAMP release |
↑ immune priming signals |
↔ (tissue-dependent) |
G |
Local-to-systemic immune modulation (adjunct potential) |
Most compelling as an adjunct (combo with checkpoint blockade, RT, etc.). Strength varies with ablation completeness, antigen burden, and microenvironment. |
| 9 |
Clinical Translation Constraint |
↔ |
↔ |
— |
Deliverability / safety / field heterogeneity |
Constraints are dominated by geometry (electrode placement, tumor shape, conductivity), safety (muscle contractions, arrhythmia risk near heart, anesthesia needs), and protocol standardization; nsPEF still has broader device/protocol variability than ECT/IRE. |