Disulfiram / selectivity Cancer Research Results

DSF, Disulfiram: Click to Expand ⟱
Features:
Disulfiram is a synthetic small-molecule drug best known for its use in the treatment of chronic alcohol use disorder. It is a thiuram disulfide compound with the chemical formula C₁₀H₂₀N₂S₄ and acts primarily as an aldehyde dehydrogenase (ALDH) inhibitor. 
Main Actions:
-Potent copper-dependent pro-oxidant
-Targets ALDH⁺ cancer stem cells
-Strong clinical repurposing interest

Key pathways
-Cu-mediated redox cycling
-Proteasome inhibition
-Mitochondrial ROS

Chemo relevance
-Often synergistic
-Highly mechanism-dependent
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


selectivity, selectivity: Click to Expand ⟱
Source:
Type:
The selectivity of cancer products (such as chemotherapeutic agents, targeted therapies, immunotherapies, and novel cancer drugs) refers to their ability to affect cancer cells preferentially over normal, healthy cells. High selectivity is important because it can lead to better patient outcomes by reducing side effects and minimizing damage to normal tissues.

Achieving high selectivity in cancer treatment is crucial for improving patient outcomes. It relies on pinpointing molecular differences between cancerous and normal cells, designing drugs or delivery systems that exploit these differences, and overcoming intrinsic challenges like tumor heterogeneity and resistance

Factors that affect selectivity:
1. Ability of Cancer cells to preferentially absorb a product/drug
-EPR-enhanced permeability and retention of cancer cells
-nanoparticle formations/carriers may target cancer cells over normal cells
-Liposomal formations. Also negatively/positively charged affects absorbtion

2. Product/drug effect may be different for normal vs cancer cells
- hypoxia
- transition metal content levels (iron/copper) change probability of fenton reaction.
- pH levels
- antiOxidant levels and defense levels

3. Bio-availability
Scientific Papers found: Click to Expand⟱
4915- DSF,  Cu,    Disulfiram: A novel repurposed drug for cancer therapy
- Review, Var, NA
ROS↑, TumCD↑, NF-kB↓, CSCs↓, ChemoSen↑, RadioS↑, eff↑, selectivity↑, Proteasome?,
5008- DSF,  Cu,    Overcoming the compensatory elevation of NRF2 renders hepatocellular carcinoma cells more vulnerable to disulfiram/copper-induced ferroptosis
- in-vitro, HCC, NA
selectivity↑, TumCD↑, TumCMig↓, TumCI↓, angioG↓, mtDam↑, Iron↑, lipid-P↑, Ferroptosis↑, NF-kB↑, p‑p62↑, Keap1↓, eff↑, eff↓, ChemoSen↑,

Showing Research Papers: 1 to 2 of 2

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 2

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

Ferroptosis↑, 1,   Iron↑, 1,   Keap1↓, 1,   lipid-P↑, 1,   ROS↑, 1,  

Mitochondria & Bioenergetics ⓘ

mtDam↑, 1,  

Cell Death ⓘ

Ferroptosis↑, 1,   Proteasome?, 1,   TumCD↑, 2,  

Autophagy & Lysosomes ⓘ

p‑p62↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

CSCs↓, 1,  

Migration ⓘ

TumCI↓, 1,   TumCMig↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 1,  

Immune & Inflammatory Signaling ⓘ

NF-kB↓, 1,   NF-kB↑, 1,  

Drug Metabolism & Resistance ⓘ

ChemoSen↑, 2,   eff↓, 1,   eff↑, 2,   RadioS↑, 1,   selectivity↑, 2,  
Total Targets: 21

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: selectivity, selectivity
Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:387  Target#:1110  State#:%  Dir#:2
  wNotes=0  sortOrder:rid,rpid

 

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