Database Query Results : Aspirin -acetylsalicylic acid, , COX1

ASA, Aspirin -acetylsalicylic acid: Click to Expand ⟱
Features: nonsteroidal anti-inflammatory drug (NSAID)
Aspirin irreversibly inhibits COX-1 and modifies the enzymatic activity of COX-2. COX-2 normally produces prostanoids, most of which are proinflammatory.

-Aspirin irreversibly inhibits the enzyme cyclooxygenase-1 (COX-1). This inhibition reduces the production of thromboxane A₂, a potent promoter of platelet aggregation.
-low-dose aspirin is frequently used for the prevention of cardiovascular events such as heart attacks and strokes in individuals at risk.

Aspirin (acetylsalicylic acid; ASA) — an acetylating salicylate NSAID that irreversibly inhibits cyclooxygenase (COX) enzymes, producing anti-inflammatory, analgesic/antipyretic, and (at low dose) antiplatelet effects via sustained suppression of platelet thromboxane A₂ (TXA₂). It is a small-molecule oral drug (OTC and prescription formulations; immediate-release and enteric-coated). Standard abbreviations include ASA and “low-dose aspirin” (typically 75–100 mg/day in many guidelines/trials). In cancer biology, the most industry-relevant hypotheses center on platelet COX-1/TXA₂ suppression (metastasis/immune effects) plus COX-2/PGE₂ suppression (inflammatory tumor microenvironment), with clinical signals that are context- and biomarker-dependent.

Primary mechanisms (ranked):

  1. Platelet COX-1 acetylation → TXA₂ ↓ → platelet activation/aggregation ↓ (systemic antiplatelet axis; downstream effects on thrombosis and platelet–tumor biology)
  2. COX-2 activity modulation/inhibition → prostanoid signaling (including PGE₂) ↓ (anti-inflammatory and tumor-microenvironment effects; more dose/context dependent than platelet COX-1)
  3. Platelet-derived TXA₂ immunosuppression axis ↓ (T-cell suppression relieved; metastasis permissiveness reduced) (context-dependent; mechanistically linked to platelet COX-1/TXA₂)
  4. Immune checkpoint/inflammation coupling: PD-L1 ↓ and inflammatory mediators ↓ (model- and tissue-dependent; partly COX/prostanoid-linked and partly epigenetic/transcriptional)
  5. Pro-apoptotic balance shift in some models (BAX ↑, Bcl-2 ↓, apoptosis ↑) (secondary; model-dependent)

Bioavailability / PK relevance: Oral absorption is generally rapid (formulation-dependent). Aspirin itself is short-lived in plasma due to rapid deacetylation to salicylate, while platelet COX-1 inhibition persists for the platelet lifespan (functional persistence despite short plasma exposure). Salicylate elimination can become dose-dependent (capacity-limited) at higher doses, extending effective half-life and increasing toxicity/bleeding risk.

In-vitro vs systemic exposure relevance: Many anti-proliferative or direct tumor-cell cytotoxic effects reported in vitro occur at concentrations not typically achieved with low-dose antiplatelet regimens; clinically plausible cancer effects at low dose are more consistent with platelet/immune/microenvironment mechanisms than direct tumor cytotoxicity.

Clinical evidence status: Strong clinical use exists for antiplatelet indications (cardiovascular secondary prevention and other clinician-directed uses). For primary prevention, contemporary guidance restricts initiation due to bleeding risk (age/risk stratified). For oncology, evidence supports chemopreventive associations (strongest for colorectal cancer in long-term use) and emerging biomarker-stratified adjuvant signals (e.g., PI3K-pathway–altered CRC recurrence reduction in a large randomized setting), but this is not universal across populations and may be age- and context-dependent.

**There is debate about the reduced cancer risk effects of aspirin when used long term (10yr). The evidence is stronger for CRC especially for those with IBD. Evidence is more debatable for those 70yrs old. Also there are claims about the anti-Metastasis capabilites of aspirin for those with cancer.

Mechanistic and translation-relevant axes for aspirin (ASA) in cancer

Rank Pathway / Axis Cancer Cells Normal Cells TSF Primary Effect Notes / Interpretation
1 Platelet COX-1 → TXA₂ Indirect: platelet shielding of CTCs ↓; platelet-assisted extravasation/metastatic seeding ↓ (context-dependent) Platelet aggregation ↓; hemostasis capacity ↓ (bleeding risk ↑) P Antiplatelet state via irreversible COX-1 acetylation High mechanistic centrality at low dose because platelets cannot resynthesize COX-1; effects persist beyond plasma aspirin exposure.
2 COX-2 → PGE₂ inflammatory tumor microenvironment Inflammatory prostanoid signaling ↓; pro-tumor inflammation ↓ (dose/context dependent) GI mucosal protection ↓ (ulcer/bleeding risk ↑); renal prostaglandin effects (risk in susceptible patients) R Anti-inflammatory prostanoid suppression COX-2 modulation is less selectively targeted than platelet COX-1 at “low-dose”; relevance increases with higher systemic exposure.
3 Platelet TXA₂ → T-cell suppression axis Anti-metastatic immunity ↑ (T-cell effector function ↑; metastasis permissiveness ↓) Immune modulation ↔ (context-dependent) R Release of T-cell suppression linked to platelet TXA₂ Mechanistic bridge between antiplatelet action and metastasis control; aligns with platelet-first hypothesis for low-dose aspirin.
4 PI3K-pathway–altered CRC recurrence signal Recurrence risk ↓ in PI3K-altered localized CRC (biomarker-stratified benefit) Systemic bleeding risk ↑ remains G Genotype-linked clinical leverage (adjuvant context) Represents actionable stratification logic: benefit concentrated in molecular subsets rather than pan-CRC.
5 Immune checkpoint coupling: PD-L1 PD-L1 ↓ (model-dependent) → immune evasion ↓ (context-dependent) Immune effects ↔ G Potential immunomodulatory adjunct axis Reported in specific tumor models via transcription/epigenetic regulators; translation likely tumor-type and context dependent.
6 Apoptosis balance Apoptosis ↑; BAX ↑; Bcl-2 ↓ (model-dependent) Cell stress/irritation ↔ (context-dependent) G Secondary pro-death signaling in some models Often requires higher concentrations than antiplatelet dosing; treat as supportive rather than primary for real-world low-dose exposure.
7 Clinical Translation Constraint Benefit heterogeneity ↑ (tumor subtype, age, bleeding risk, concomitant therapy) GI bleeding ↑; hemorrhagic stroke risk ↑ (baseline-dependent); hypersensitivity in susceptible patients G Therapeutic window constrained by bleeding and population selection Major limiter for preventive use in older adults; drug–drug interactions (anticoagulants/other NSAIDs) and peri-procedural management are practical constraints.

TSF legend: P: 0–30 min   R: 30 min–3 hr   G: >3 hr
COX1, COX-1: Click to Expand ⟱
Source:
Type:
COX‑1 is traditionally considered a constitutively expressed enzyme involved in “housekeeping” functions, while COX‑2 is more frequently studied in relation to cancer.
• The prognostic impact of COX‑1 may vary based on cancer subtype, stage, and interplay with other inflammatory mediators (e.g., COX‑2).
• Many studies assess combined cyclooxygenase profiles (COX‑1/COX‑2) rather than COX‑1 alone.
Scientific Papers found: Click to Expand⟱
5405- ASA,    Exploring Aspirin’s Potential in Cancer Prevention: A Comprehensive Review of the Current Evidence
- Review, Var, NA
Risk↓, emerging evidence suggests that aspirin may reduce the risk of certain cancers, particularly colorectal cancer (CRC).
COX1↓, Aspirin’s anticancer effects are primarily attributed to its cyclooxygenase (COX) enzyme inhibition, which decreases prostaglandin E2 (PGE2) levels and disrupts cancer-related signaling pathways.
PGE2↓,
Inflam↓, Aspirin is a versatile medication commonly used as an analgesic, anti-inflammatory, antipyretic, and antiplatelet agent [2,3].
*AntiAg↓,
PI3K↓, By irreversibly inhibiting COX-2, aspirin reduces PGE2 levels, thereby decreasing the activation of cancer-related signaling pathways such as PI3K/AKT (phosphatidylinositol 3-kinase/protein kinase B) and ERK and promoting apoptosis in cancer cells ​
Akt↓,
Risk↓, For pancreatic cancer, aspirin for at least five years significantly reduces the risk of death, though this protective effect becomes apparent only after a five-year lag period [39].

5415- ASA,    The Anti-Metastatic Role of Aspirin in Cancer: A Systematic Review
- Review, Var, NA
TumMeta↓, The included studies demonstrated that aspirin suppresses metastatic dissemination across multiple cancer types through coordinated platelet-dependent and tumor-intrinsic mechanisms.
COX1↓, Aspirin consistently inhibited platelet aggregation and COX-1-dependent TXA2 production, disrupting platelet–tumor cell interactions, intravascular metastatic niche formation, and platelet-mediated immune suppression.
TXA2↓,
AntiAg↑, Beyond platelet effects, aspirin suppressed EMT, migration, and invasion through modulation of EMT transcriptional regulators and inflammatory signaling pathways.
EMT↓,
TumCMig↓,
TumCI↓,
AMPK↑, Additional mechanisms included activation of AMPK, inhibition of c-MYC signaling, regulation of redox-responsive pathways and impairment of anoikis resistance.
cMyc↓,
PGE2↓, Importantly, oral aspirin (20 mg/kg/day; human-equivalent ≈ 150 mg/day), administered before tumor cell injection, prevented platelet-induced metastatic enhancement and suppressed TXA2 and PGE2 production.
Dose↑, medium and high doses of aspirin reduced pulmonary metastatic burden by more than 50%, whereas low-dose aspirin was ineffective.
RadioS↑, Wang et al. [45] demonstrated that low-dose aspirin suppresses radiotherapy-induced release of immunosuppressive exosomes in breast cancer, restoring NK-cell proliferation and enhancing antitumor immunity in vivo.
PD-L1↓, Similarly, Xiao et al. [46] showed that aspirin epigenetically downregulates PD-L1 expression by inhibiting KAT5-dependent histone acetylation, thereby restoring T-cell activation
E-cadherin↑, Aspirin restored E-cadherin expression and suppressed EMT regulators, including Slug, vimentin, Twist, MMP-2, and MMP-9.
EMT↓,
Slug↓,
Vim↓,
Twist↓,
MMP2↓,
MMP9↓,
other↑, definitive conclusions regarding clinical efficacy across cancer types cannot yet be drawn. Nevertheless, the consistency of mechanistic signals across experimental systems supports further investigation of aspirin as a low-cost adjunct in oncology

5414- ASA,    Aspirin and cancer treatment: systematic reviews and meta-analyses of evidence: for and against
- Review, Var, NA
Risk↓, Meta-analyses of 118 observational studies of mortality in cancer patients give evidence consistent with reductions of about 20% in mortality associated with aspirin use.
*toxicity↓, Reasons against aspirin use include increased risk of a gastrointestinal bleed though there appears to be no valid evidence that aspirin is responsible for fatal gastrointestinal bleeding.
other↑, In conclusion, given the relative safety and the favourable effects of aspirin, its use in cancer seems justified, and ethical implications of this imply that cancer patients should be informed of the present evidence
*COX1↓, recent evidence highlights additional targets for aspirin in tackling cancer progression directly, irrespective of COX activity [3, 4]
TumCP↓, Such targets include energy metabolism involved in cancer proliferation, cancer associated inflammation [5] and platelet driven pro-carcinogenic activity [2].
DNArepair↑, beneficial effect of aspirin on colon cancer risk through an enhancement of DNA-repair mechanisms [2].
ChemoSen↑, ‘basic science’ basis to justify using aspirin as an adjunct to other pre-existing therapies (e.g., immunotherapy and cytotoxic chemotherapy) in the treatment of cancer progression and metastasis [2, 14].
other↓, Aspirin has been shown repeatedly to reduce thromboembolism, including in patients with cancer [15]

5413- ASA,    Drug Resistance and Pseudoresistance: An Unintended Consequence of Enteric Coating Aspirin
- Trial, Nor, NA
*cardioP↑, Low dose aspirin reduces the secondary incidence of myocardial infarction and stroke.
*other↝, Pseudoresistance, reflecting delayed and reduced drug absorption, complicates enteric coated but not immediate release aspirin administration.
*COX1↓, irreversible acetylation of Ser530 in the enzyme prostaglandin G/H synthase-1 (commonly termed cyclooxygenase [COX]-1) and the consequent suppression of thromboxane (Tx) A2 (TxA2) formation.
*TXA2↓,

5412- ASA,    Clinical Pharmacology of Aspirin
- Review, NA, NA
*COX1↓, Aspirin is the acetate ester of salicylic acid and acts by binding irreversibly to cyclooxygenase-1 and cyclooxygenases-2
*COX2↓,
*cardioP↑, Aspirin is consumed most often at low-doses for cardio-protection and at higher doses as an analgesic, antipyretic, and anti-inflammatory agents.
*BioAv↑, Orally ingested aspirin is absorbed rapidly and the peak concentration is reached in about 1 hour.
*BioAv↝, a rise in pH also increases the solubility of aspirin and thus the dissolution of the tablets and the presence of food delays absorption of aspirin.
*Half-Life↓, The elimination half-life of aspirin in plasma is about 20 min
Risk↓, Patients who received 100 mg daily of aspirin had reduced risks of colorectal cancer and gastric cancer and an increased risk of gastrointestinal bleeding [6].
*other↑, Low-dose of aspirin treatment significantly improves ovarian responsiveness, uterine and ovarian blood flow velocity, and pregnancy-rates in women undergoing in-vitro fertilization [19].
*AntiAg↑, antiplatelet effect of aspirin [13],

5411- ASA,    Mechanistic Insights into a Classic Wonder Drug—Aspirin
- Review, Var, NA
*COX2↓, The principal pharmacological effects of aspirin are known to arise from its covalent modification of cyclooxygenase-2 (COX-2) through acetylation of Ser530, but the detailed mechanism of its biochemical action and specificity remains to be elucidate
*COX1↓, The computational results confirmed that aspirin would be 10–100 times more potent against COX-1 than against COX-2,
*Inflam↓, esides its wide use in the treatment of inflammation, fever, and pain for over a century and its well-known benefit in the prevention/treatment of cardiovascular diseases,
*cardioP↑,
Risk↓, regular aspirin intake has recently been convincingly shown to reduce the overall risk of certain cancers. (1a-1e)

5408- ASA,    An aspirin a day keeps cancer at bay
- Review, Var, NA
TumMeta↓, It has long been hypothesised that aspirin prevents cancer deaths by preventing metastasis.
TXA2↓, A recent study demonstrates this to be mediated through inhibition of Thromboxane A2 (TXA2) leading to reversal of suppression of T cell immunity.
*AntiAg↑, It was therefore hypothesised [3, 5] that aspirin prevents cancer metastasis, very likely through its anti-platelet action but the exact mechanism of action remained unclear.
COX1↓, anti-platelet activity through inhibition of cyclooxygenase-1 (COX-1) remains the main plausible mechanism.

5402- ASA,    Aspirin prevents metastasis by limiting platelet TXA2 suppression of T cell immunity
- Review, Var, NA
COX1↓, Here we show that inhibitors of cyclooxygenase 1 (COX-1), including aspirin, enhance immunity to cancer metastasis by releasing T cells from suppression by platelet-derived thromboxane A2 (TXA2).
TumMeta↓, Moreover, low-dose (75–300 mg) aspirin treatment is associated with a reduction in the rate of cancer death in individuals without metastasis at the time of cancer diagnosis
*Half-Life↓, Aspirin has a short half-life (around 20 min), such that only frequent high doses of aspirin can achieve sustained pharmacological inhibition of COX-1 and COX-2 in nucleated cells
*COX2↓, Aspirin can inhibit both COX-1 and COX-2
*TXA2↓, suppression by platelet-derived thromboxane A2 (TXA2).

5401- ASA,    Residual cyclooxygenase activity of aspirin-acetylated COX-2 forms 15R-prostaglandins that inhibit platelet aggregation
- Review, Nor, NA
*AntiAg↑, 15R-PGs are novel products of aspirin therapy via acetylation of COX-2 and may contribute to its antiplatelet and other pharmacologic effects.
*COX1↓, Aspirin inhibits the cyclooxygenase (COX) enzymes via a unique mechanism

5400- ASA,    Beyond COX-1: the effects of aspirin on platelet biology and potential mechanisms of chemoprevention
- Review, Nor, NA
Risk↓, dramatically reduced incidence of cancer in individuals taking daily low-dose aspirin [1–7],
*Inflam↓, Aspirin, like the vast majority of NSAIDs, is thought to exert its anti-inflammatory effects through inhibition of cyclooxygenase enzymes (COX enzymes) that regulate the production of prostaglandins.
*COX1↓,
*AntiAg↑, spirin acts to blunt a variety of pro-inflammatory responses, including the canonical inflammatory response [9–11], production of a defensive mucosal lining [12], and platelet aggregation [13, 14].
*Half-Life↓, The half-life of aspirin in the bloodstream was previously shown to be 13–19 min with a non-enzymatic hydrolysis rate of 0.023 min−1 at 37 °C in individuals given a single oral administration of aspirin.
*BioAv↑, Approximately 70% of aspirin reaches the peripheral circulation intact with maximum serum concentrations observed at 25 min after administration.

2461- ASA,    Aspirin and platelets: the antiplatelet action of aspirin and its role in thrombosis treatment and prophylaxis
- Review, NA, NA
AntiAg↑, The antithrombotic action of aspirin (acetylsalicylic acid) is due to inhibition of platelet function by acetylation of the platelet cyclooxygenase (COX)
COX1↓, Aspirin is an approximately 150- to 200-fold more potent inhibitor of the (constitutive) isoform of the platelet enzyme (COX-1) than the (inducible) isoform (COX-2)
eff↑, Aspirin is the "gold standard" antiplatelet agent for prevention of arterial thromboses.

1096- ASA,    Aspirin inhibit platelet-induced epithelial-to-mesenchymal transition of circulating tumor cells (Review)
- Review, NA, NA
TumMeta↓, regular aspirin use was associated with a reduced risk of cancer metastasis
COX1↓,
CTC↓,


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 12

Pathway results for Effect on Cancer / Diseased Cells:


Core Metabolism/Glycolysis ⓘ

AMPK↑, 1,   cMyc↓, 1,  

Cell Death ⓘ

Akt↓, 1,  

Transcription & Epigenetics ⓘ

other↓, 1,   other↑, 2,  

DNA Damage & Repair ⓘ

DNArepair↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

EMT↓, 2,   PI3K↓, 1,  

Migration ⓘ

AntiAg↑, 2,   E-cadherin↑, 1,   MMP2↓, 1,   MMP9↓, 1,   Slug↓, 1,   TumCI↓, 1,   TumCMig↓, 1,   TumCP↓, 1,   TumMeta↓, 4,   Twist↓, 1,   Vim↓, 1,  

Angiogenesis & Vasculature ⓘ

TXA2↓, 2,  

Immune & Inflammatory Signaling ⓘ

COX1↓, 6,   Inflam↓, 1,   PD-L1↓, 1,   PGE2↓, 2,  

Drug Metabolism & Resistance ⓘ

ChemoSen↑, 1,   Dose↑, 1,   eff↑, 1,   RadioS↑, 1,  

Clinical Biomarkers ⓘ

CTC↓, 1,   PD-L1↓, 1,  

Functional Outcomes ⓘ

Risk↓, 6,  
Total Targets: 31

Pathway results for Effect on Normal Cells:


Transcription & Epigenetics ⓘ

other↑, 1,   other↝, 1,  

Migration ⓘ

AntiAg↓, 1,   AntiAg↑, 4,  

Angiogenesis & Vasculature ⓘ

TXA2↓, 2,  

Immune & Inflammatory Signaling ⓘ

COX1↓, 6,   COX2↓, 3,   Inflam↓, 2,  

Drug Metabolism & Resistance ⓘ

BioAv↑, 2,   BioAv↝, 1,   Half-Life↓, 3,  

Functional Outcomes ⓘ

cardioP↑, 3,   toxicity↓, 1,  
Total Targets: 13

Scientific Paper Hit Count for: COX1, COX-1
12 Aspirin -acetylsalicylic acid
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#:1  Target#:998  State#:%  Dir#:%
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