doxorubicin / GSTA1 Cancer Research Results

doxoR, doxorubicin: Click to Expand ⟱
Features:
Doxorubicin, (brand name Adriamycin) is a chemotherapy medication used to treat breast cancer, bladder cancer, Kaposi's sarcoma, lymphoma, and acute lymphocytic leukemia. Often used together with other chemotherapy agents. Given by injection into a vein.
Doxorubicin is an anthracycline chemotherapy whose core anticancer activity is driven by DNA intercalation and topoisomerase II poisoning (DNA double-strand break stress), with additional contributions from redox cycling/iron-linked oxidative injury in some contexts. Its major clinical limitations are myelosuppression and cumulative dose–dependent cardiomyopathy, plus severe tissue injury if extravasated (leaks outside the vein).
-Cumulative cardiomyopathy risk is real and dose-dependent; labels note higher risk at higher cumulative doses (often cited around >550 mg/m², with lower limits in higher-risk patients).
-Mechanism split: tumor kill is primarily Topo II + DNA damage, while cardiotoxicity is strongly linked to TOP2β/mitochondrial pathways (redox/iron biology remains discussed, but not the only story).
-Administration hazard: extravasation can cause severe local injury;

Rank Pathway / Axis Cancer / Tumor Context Normal Tissue Context TSF Primary Effect Notes / Interpretation
1 Topoisomerase II poisoning (DNA double-strand break stress) Topo II–DNA cleavage complexes ↑ → DNA breaks ↑ → apoptosis/senescence ↑ (context) Also affects normal proliferating tissues (marrow, mucosa) P, R Core cytotoxic mechanism Primary anticancer mechanism: stabilization of Topo II–DNA cleavage complexes blocks repair and drives lethal DNA damage responses.
2 DNA intercalation → replication/transcription disruption DNA/RNA synthesis ↓; replication stress ↑ Off-target in normal dividing cells P, R Replication/transcription blockade Intercalation contributes to replication fork stress and complements Topo II poisoning.
3 Redox cycling / iron-associated oxidative injury (context-dependent) ROS / oxidative damage ↑ (reported; model-dependent) Oxidative injury risk in sensitive tissues (esp. heart) ↑ P, R, G Stress amplification Often described as semiquinone redox cycling and iron interactions; the relative importance vs Topo II varies by tissue/model.
4 Cardiotoxicity axis (TOP2β + mitochondrial injury; cumulative-dose dependent) — Risk of cardiomyopathy/heart failure ↑ with cumulative exposure R, G Major dose-limiting toxicity Clinically important boxed-warning toxicity; risk increases with cumulative dose (labels cite higher risk above ~550 mg/m²; higher-risk patients often use lower limits).
5 Myelosuppression (bone marrow progenitors) — Neutropenia/anemia/thrombocytopenia risk ↑ R, G Dose-limiting toxicity Expected on-target effect in rapidly dividing marrow cells; infection risk increases when neutrophils are low.
6 p53 / DNA-damage response programs DDR signaling ↑; p53 pathway engagement ↑ (context) DDR activation in normal tissues contributes to toxicity R, G Cell fate commitment Downstream of DNA breaks: checkpoint activation, apoptosis, senescence, or mitotic catastrophe depending on genotype and dose.
7 Immunogenic cell death signals (DAMP exposure; context-dependent) Potential ICD features ↑ (reported in some systems) — G Immune engagement (conditional) Anthracyclines are often discussed as capable of immunogenic cell death in certain settings; not universal across regimens.
8 Extravasation tissue injury (local) — Severe local tissue damage risk if IV leakage occurs P, R Administration hazard Boxed warning emphasizes severe tissue injury with extravasation; requires strict IV administration controls.
9 Secondary malignancy risk (therapy-related AML/MDS; exposure-dependent) — Rare long-term risk signal ↑ — Late toxicity constraint Listed in boxed warnings/labels as a potential late effect, especially with combination regimens.
10 Cardioprotection strategy (dexrazoxane; selected settings) — Cardiotoxicity risk ↓ (when used appropriately) R, G Risk mitigation Dexrazoxane is used to reduce anthracycline cardiotoxicity; mechanistic literature includes TOP2β-linked protection and other hypotheses.

Time-Scale Flag (TSF): P / R / G

  • P: 0–30 min (direct DNA/Topo interactions begin rapidly)
  • R: 30 min–3 hr (acute DNA-damage response + stress signaling)
  • G: >3 hr (gene programs, apoptosis/senescence, phenotype-level outcomes)
GSTA1, Glutathione S-Transferase A1: Click to Expand ⟱
Source:
Type:
GSTA1 belongs to the glutathione S-transferase (GST) superfamily of enzymes. These enzymes catalyze the conjugation of glutathione (GSH) to a variety of electrophilic substrates, thereby aiding in their detoxification.
By facilitating the detoxification of reactive metabolites, carcinogens, and drugs, GSTA1 helps protect cells against oxidative stress and chemical-induced damage.
In tumor cells, upregulation of GSTA1 may be a defensive response to increased oxidative stress. While this can protect normal cells, in a tumor setting, enhanced detoxification may allow cancer cells to survive in a hostile microenvironment.
Elevated levels of GSTA1 have been linked to resistance to chemotherapy. As GSTA1 helps metabolize and clear chemotherapeutic agents, its overexpression in tumors can contribute to treatment resistance
-GSTA1 expression levels are being evaluated as a prognostic marker. In some studies, its overexpression has correlated with aggressive tumor behavior, higher rates of recurrence, and reduced overall survival.
Scientific Papers found: Click to Expand⟱
8190- LGE,  doxoR,    Cymbopogon citratus and Citral Overcome Doxorubicin Resistance in Cancer Cells via Modulating the Drug's Metabolism, Toxicity, and Multidrug Transporters
- in-vitro, BC, MCF7 - in-vitro, Liver, HepG2 - in-vitro, Ovarian, SKOV3
ChemoSen↑, CYP3A4↓, PXR, NR1I2↓, GSTA1↓, MDR1↓, MRP1/ABCC1↓, ABCG2↓,

Showing Research Papers: 1 to 1 of 1

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 1

Pathway results for Effect on Cancer / Diseased Cells:


NA, unassigned(tgid=0) ⓘ

PXR, NR1I2↓, 1,  

Redox & Oxidative Stress(tgid=1) ⓘ

GSTA1↓, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

CYP3A4↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

ABCG2↓, 1,   ChemoSen↑, 1,   MDR1↓, 1,   MRP1/ABCC1↓, 1,  
Total Targets: 7

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: GSTA1, Glutathione S-Transferase A1
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#:179  Target#:1091  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

 

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