| Rank |
Pathway / Axis |
Cancer Cells |
Normal Cells |
Label |
Primary Interpretation |
Notes |
| 1 |
Metal chelation / Disulfiram–Cu complex formation |
↑ DSF–Cu complex formation |
↔ limited formation |
Driver |
Copper-dependent cytotoxic chemistry |
Elevated copper in cancer cells enables formation of cytotoxic DSF–Cu complexes; this is the initiating event for most anticancer effects |
| 2 |
Proteasome / p97–NPL4 axis |
↓ proteasome function; ↑ proteotoxic stress |
↔ minimal disruption |
Driver |
Protein homeostasis collapse |
DSF–Cu disrupts protein degradation pathways, leading to accumulation of misfolded proteins and stress signaling |
| 3 |
Reactive oxygen species (ROS) |
↑ ROS (metal-dependent) |
↔ buffered |
Secondary |
Oxidative stress amplification |
ROS rise follows DSF–Cu redox cycling and proteotoxic stress; not the primary trigger |
| 4 |
Mitochondrial integrity / intrinsic apoptosis |
↓ ΔΨm; ↑ caspase activation |
↔ preserved |
Secondary |
Execution of cell death |
Mitochondrial dysfunction and apoptosis occur downstream of proteostasis and redox stress |
| 5 |
ALDH activity (ALDH1A1 / stemness) |
↓ ALDH activity |
↓ ALDH (clinically tolerated) |
Secondary |
Cancer stem-like cell targeting |
ALDH inhibition preferentially impacts cancer stem-like populations; normal cells tolerate inhibition at therapeutic exposure |
| 6 |
NF-κB signaling |
↓ NF-κB activation |
↓ inflammatory NF-κB tone |
Secondary |
Suppression of survival transcription |
NF-κB inhibition reflects upstream proteotoxic and redox stress rather than direct targeting |
| 7 |
Cell cycle progression |
↓ proliferation / ↑ arrest |
↔ largely spared |
Phenotypic |
Cytostatic growth control |
Growth inhibition reflects impaired protein turnover and metabolic stress |
| 8 |
Apoptosis / non-apoptotic death |
↑ apoptosis or proteotoxic death |
↔ protected |
Phenotypic |
Threshold-dependent cell death |
Cell death modality depends on copper availability and stress magnitude |