Database Query Results : Aspirin -acetylsalicylic acid, , Risk

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
Risk, Risk: Click to Expand ⟱
Source:
Type:
Risk: by definition reduces risk of disease or cancer.
Down Target direction of risk indicates lower cancer risk.
ChemoPreventive also mean lower cancer risk. But for Chemopreventive an up arrow indicates more preventive. 
Cancer Risk Impact Score (CRIS)
CRIS scale:
–5 = very strong risk reduction
–4 = strong risk reduction
–3 = moderate risk reduction
–2 = modest risk reduction
–1 = weak / context-dependent
0 = neutral




CRIS Exposure / Compound Evidence Cancers Notes




-5 Exercise (overall)
VStrong Hum BC, CRC, Endo, PCa, Liv






-5 Aerobic + resistance VStrong Hum Broad inc + mort






-4 Aerobic exercise (mod–vig) VStrong Hum BC, CRC, Endo






-4 Resistance training (alone) Strong Hum BC, CRC






-3 High-intensity interval training Mod–Strong Hum BC, CRC






-2 NEAT / low-intensity activity Moderate Hum CRC






-5 Cruciferous vegetable pattern Strong Hum Lung, CRC, BC, PCa






-5 Sunlight exposure (physiologic) Strong Hum CRC, BC, PCa






-4 Fasting (metabolic pattern)
Strong Mech + Hum BC, CRC, PCa 






-4 Curcumin
Hum + Pre GI, BC, PCa






-4 Sulforaphane
Hum + Pre Lung, CRC, BC






-4 PEITC
Hum + Pre Lung, CRC, PCa






-4 EGCG (tea matrix)
Strong Hum GI, PCa, BC






-4 Lycopene
Strong Hum PCa






-4 Apigenin
Pre + Diet Hum BC, PCa, CRC 






-4 Luteolin
Pre + Diet Hum Lung, CRC, BC 






-4 Kaempferol
Diet Hum Ov, Panc, Lung






-4 Fisetin
Pre + Early Hum CRC, PCa, Mel






-4 Ellagic acid → Urolithin A
Hum (microbiome) CRC, PCa, BC






-3 Omega-3 (EPA/DHA)
Strong Hum CRC, BC






-3 Vitamin D3 (supp)
Obs + RCT CRC, BC






-3 Garlic (allicin)
Mod Hum GI






-3 Mushroom beta-glucans
Hum adjunct GI, BC






-3 Melatonin
Hum + Mech BC, PCa






-3 Coffee (whole)
Strong Hum Liv, Endo






-2 Quercetin
Limited Hum Lung, CRC






-2 Resveratrol
Limited Hum CRC, BC






-2 I3C / DIM
Mod Hum BC, Cerv






-2 Thymoquinone
Early Hum BC, CRC






-2 Beta-carotene (food)
Hum Lung






-1 Vitamin K2 (MK-4/7)
Limited Hum Liv, PCa






-1 Boron
Obs PCa, Lung






0 Vitamin C (oral)
Strong Hum —






0 Genistein (soy)
Strong Hum BC, PCa






0 Selenium (diet)
Mixed Hum PCa






0 Capsaicin
Mixed Gastric






+2 Vitamin E (alpha only)
Strong RCT PCa






+2 Green tea extract (high-dose)
Case reports Liv






+4 Beta-carotene (supplement)
Strong RCT Lung (smokers)






+5 Alcohol (ethanol)
Strong Hum BC, Liv, Eso







Evidence
Hum        human data
VStrong    very strong
Strong     strong
Mod        moderate
Obs        observational
Pre        preclinical
RCT        randomized controlled trial
Mech       mechanistic
Adjunct    adjunct clinical use


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].

5416- ASA,    Cancer Incidence and Mortality With Aspirin in Older Adults
- Trial, Var, NA
Risk∅, In this study, over a median of 8.6 years, LDA was not associated with incident cancer among older adults, but cancer mortality risk was significantly elevated.
OS∅, However, the elevated cancer mortality risk seen with aspirin for participants in the RCT period did not persist into the post-RCT observation period, suggesting no legacy effect.

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]

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)

5410- ASA,    Low-Dose Aspirin and the Prevention of Colorectal Cancer in Inflammatory Bowel Disease: A Nationwide Cohort Study
- Study, CRC, NA
Risk↓, 2743 matched aspirin users and 2743 nonusers, aspirin use was associated with reduced CRC risk (adjusted hazard ratio, 0.42
Dose↝, A dose-response relationship was found for cumulative exposure, while optimal daily intensity was near 80 mg/d.
Risk↓, Long-term use of low-to-moderate-dose aspirin was associated with reduced risks of CRC and mortality in patients with IBD.

5409- ASA,    Role of aspirin in cancer prevention
- Review, Var, NA
Imm↑, It was proved that aspirin showed advantages in immunomodulation, cell metabolism, gene repair, reduction of inflammatory reaction, anti-platelet activation and improvement of intestinal flora.
*Inflam↓,
*AntiAg↑, Clinicians have found that aspirin not only has anti-platelet aggregation, antipyretic, and analgesic effects, but also has a potential additional effect on the prevention and treatment of cancer.
*GutMicro↑,
eff↑, combination of aspirin and existing anti-tumor drugs also showed some synergistic effects.
TumMeta↓, The results showed that the aspirin group decreased the rate of distant metastasis, especially for colorectal cancer [3].
angioG↓, Studies have shown that aspirin can bind directly to the GLU150(Q9y251: Glu 225) region to inhibit heparanase activity and regulate related signalling pathways, thereby inhibiting angiogenesis and tumour metastasis [4].
Risk↓, A study published in the JAMA Network Open suggested that frequent aspirin use (defined as daily or almost daily use for 6 months or longer) was associated with a 13 % lower risk of ovarian cancer, and this protective association was not affected by
Risk↓, 1982 to 2009, and it was found that compared with non-aspirin users, men who take aspirin regularly (more than three tablets per week) have a lower risk of fatal prostate cancer.

5407- ASA,    Low-dose aspirin reduces the risk of colorectal cancer recurrence in patients with resected PI3K-altered localised disease, according to the ALASCCA trial.
- Trial, CRC, NA
Dose↝, randomly assigned patients with prespecified PIK3CA hotspot mutations in exon 9 or 20 (group A) or other moderate-to-high impact variants in PIK3CA, PIK3R1, or PTEN (group B) to receive either aspirin 160 mg (157 in group A, 156 in group B) or placeb
Risk↓, 3-year cumulative incidence of recurrence in group A was 7·7% with aspirin versus 14·1% with placebo

5404- ASA,    Low-Dose Aspirin and Prevention of Colorectal Cancer: Evidence From a Nationwide Registry-Based Cohort in Norway
- Study, CRC, NA
Risk↓, Current use of aspirin vs never use was associated with lower CRC risk (hazard ratio [HR] 0.87, 95% confidence interval
other↝, However, some large cohorts found no association between aspirin use and CRC risk when aspirin was initiated after 70 years of age (9) and when aspirin was used for less than 10 years (10) or 20 years (11).
Dose↝, Use of 160 mg tablets was associated with a greater CRC risk reduction than the use of 75 mg tablets.
Risk↓, We found a 13% lower CRC risk associated with current low-dose aspirin use vs never use,
other↓, In 2020, a large meta-analysis of 15 cohort, 11 nested case-control, and 19 case-control studies reported a 27% reduced CRC risk in regular users of aspirin (7)
other↝, It was argued later that the limited follow-up time of participants without history of aspirin use before the trial enrollment could partly explain the negative results in the ASPREE trial (9,36).
KRAS↓, A mechanism supporting the hypothesis that aspirin has a protective effect against CRC risk is that aspirin blocks the mutated APC (adenomatous polyposis coli) gene, leading to the inhibition of the KRAS pathway and the adenomatous polyp formation (3
other↓, By assuming a protective effect of aspirin against CRC, we estimated that 1,073 cases with CRC were prevented by aspirin use, equating to 2.7% lower CRC incidence.
other↓, In conclusion, our study provided novel and strong evidence that low-dose aspirin use is associated with a lower CRC risk.

5403- ASA,    Low-Dose Aspirin for PI3K-Altered Localized Colorectal Cancer
- Trial, CRC, NA
Risk↓, The estimated 3-year cumulative incidence of recurrence was 7.7% with aspirin and 14.1% with placebo (hazard ratio, 0.49; 95% confidence interval [CI], 0.24 to 0.98; P = 0.04) among patients with group A alterations and 7.7% and 16.8%
other↝, Aspirin led to a significantly lower incidence of colorectal cancer recurrence than placebo among patients with PIK3CA hotspot mutations in exon 9 or 20 and appeared to have a similar benefit among those with other somatic alterations in PI3K pathway

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.

5399- ASA,    Effect of Aspirin on Cancer Incidence and Mortality in Older Adults
- Trial, Nor, NA
Risk↝, aspirin was associated with an increased risk of incident cancer that had metastasized
Risk↑, These findings suggest that in older persons, aspirin may accelerate the progression of cancer and, thus, suggest caution with its use in this age group.
Risk∅, There was no association of aspirin with the overall incidence of solid tumors (HR = 1.05, 95% CI = 0.95 to 1.15) or with the incidence of cancers that were diagnosed at stages 1, 2, or 3.
Risk↑, By contrast, aspirin was associated with an increase in the incidence of cancers presenting at stage 4 (HR = 1.22, 95% CI = 1.02 to 1.45).
other↝, Prostate, colorectal, breast, melanoma, and lung were the most common incident cancers, accounting for 80% of all solid tumor cancers.


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

Pathway results for Effect on Cancer / Diseased Cells:


Cell Death ⓘ

Akt↓, 1,  

Transcription & Epigenetics ⓘ

other↓, 4,   other↑, 1,   other↝, 4,  

DNA Damage & Repair ⓘ

DNArepair↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

PI3K↓, 1,  

Migration ⓘ

KRAS↓, 1,   TumCP↓, 1,   TumMeta↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX1↓, 1,   Imm↑, 1,   Inflam↓, 1,   PGE2↓, 1,  

Drug Metabolism & Resistance ⓘ

ChemoSen↑, 1,   Dose↝, 3,   eff↑, 1,  

Clinical Biomarkers ⓘ

KRAS↓, 1,  

Functional Outcomes ⓘ

OS∅, 1,   Risk↓, 14,   Risk↑, 2,   Risk↝, 1,   Risk∅, 2,  
Total Targets: 23

Pathway results for Effect on Normal Cells:


Transcription & Epigenetics ⓘ

other↑, 1,  

Migration ⓘ

AntiAg↓, 1,   AntiAg↑, 3,  

Immune & Inflammatory Signaling ⓘ

COX1↓, 4,   COX2↓, 2,   Inflam↓, 3,  

Drug Metabolism & Resistance ⓘ

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

Clinical Biomarkers ⓘ

GutMicro↑, 1,  

Functional Outcomes ⓘ

cardioP↑, 2,   toxicity↓, 1,  
Total Targets: 12

Scientific Paper Hit Count for: Risk, Risk
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#:785  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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