It is always assumed that aspirin works to prevent CRC because it is a cox inhibitor and that fish oil works in an analogous way. This may be due to a modification of prostaglandins PGE and its subsequent effect on wnt signalling. Do you have a proposed mechanism by which clopidogrel might work? I assume you have searched for epidemiological studies and found none.

Aspirin low dose is associated with lower incidence of colon cancer possibly related its cycloxygenase pathway inhibiting effect , while clopidogrel   has no effect on cox pathway.

Recent  analyses related to patients on long-term aspirin therapy have indicated a decreased incidence of colorectal cancer . These studies indicate that aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) protect against colorectal cancer to a greater degree over protection against non-gastrointestinal cancers. Recently, Petersen et al . (2005) have shown that

a low dose of aspirin protects cells against oxidative damage and induces apoptosis. These features have been shown particularly in human lens epithelial cells, illustrating the evidence of the antioxidant potential of aspirin. Various pieces of evidence suggest that aspirin possesses antiproliferative properties mediated in different cell lines, including human colorectal tumour cells

(Bellosillo et al . 1998; Din et al . 2004), gastric cancer cells (Wong et al . 1999),B-cell chronic lymphocytic leukaemia cells (Bellosillo et al . 1998), myeloid leukaemia cell lines (Klampfer et al . 1999), vascular smooth muscle cells (Marra et al . 2000; Brooks et al . 2003), colon aden- ocarcinoma cells (Shiff et al . 1996) as well as many other cell types. Generally, aspirin induces a dose-dependent reduction in the proliferation rate of HT-29 cells (Shiff et al . 1996). The sodium salt of aspirin also significantly inhibits cellular proliferation of human pancreatic cancer cell lines (BxPC3 and Panc-1) in a dose-dependent manner (Perugini et al.2000). Goel et al . (2003) found similar effects of aspirin on the growth of three different human colon cancer cell populations (HCT116, HCT116 + chr3 and SW480) but at different rates. At 72-h incubation with aspirin treatment, the proliferation rate of HCT116 + chr3 cells was significantly less than inhibition of HCT116 cells at 0.1 mm (14.3% versus 40.7%) and 2.5 mm (27.2% versus 47.9%). All other published investigations have concluded that the inhibitory effects of aspirin on cell population growth and cell proliferation is dose and time dependent

(Qiao et al . 1998; Wong et al . 1999; Zho et al. 2001; Kim et al. 2003).effects of aspirin on the proliferation of different cell lines at different doses and incubation times. Generally, the dose inducing significant antiproliferative and pro-apoptotic effects of aspirin in vitro is between 3 mm and 10 mm (Santini et al . 1999; Marra & Liao 2001; Zha et al . 2004), although in the literature there are reports of higher concentrations of up to 20 mm (Schwenger et al. 1997,1999; Pillinger et al. 1998) being effective.The mechanism by which aspirin and related NSAIDs exert their therapeutic effects in cancer was first established based on the inhibition of PG synthesis. Two isoforms of the enzyme, cyclooxygenase or COX-1 and COX-2, are responsible for the synthesis of PGs in various cells, and these enzymes have been found to play an important role in a number of malignancies(Munkarah et al. 2002). PGs are signalling molecules and are responsible for regulating a number of cellular functions, including gene expression, growth and differentiation (Towndrow et al 2000). Many cancers overproduce PGs, and this can be inhibited by aspirin.

But clopidogrel have anti platelet effect , no anti cancer effect like aspirin.

I'd say no, in the absence of comparive studies or epidemiological data, Clopidogrel is much younger than Aspirin, so its effects on cancer incidence, if any, probably can't be detected that soon.

Aspirin is a CycloOxygenase Inhibitor, that reduces the rate of Thromboxane B2 formation, thus inhibiting Platelet Aggregation, but Clopidogrel is an ADP receptor antagonist. Clopidogrel proved being better tan Aspirin in Ischemic Heart Disease, and also an article exists on anti-inflammatory activity of Clopidogrel in Inflammatory Bowel Disease (PMID 23248405), but Aspirin has a long record as anti-inflammatory drug, its first indication was pain and inflammation, while Clopidogrel lacks this indication being approved.

Genetic tests exist as to ascertain who can benefit from ASA as a preventive measure in CVD, and ASA is also know influencing pharmacology of Clopidogrel.

This question of putative, not proven anti-cancer activity of Clopidogrel may deserve either a bench or epidemiological study to obtain data about its presence.

Thanks

Sayed:

The several contributors above have already provided some valuable feedback on the issue raised in Sayed's excellent question, so I will restrict my attention to a brief summary of an internal review I recently completed on this theme in which I marshal evidence, including RCT human clinical data, that suggests a clinically relevant potential anticancer benefit from the addition of antiplatelet therapy to oncotherapy, distinct and independent from any anti-COX-2 inhibitory activity, showing that the anticancer benefit is leveraged via inhibition as well as a pro-apoptotic effect, its own set of unique molecular pathways apart from COX (se below). These lines of evidence find the clearest case for benefit stemming from the specific antiplatelet agents and ticlopidine (Ticlid(e) and especially defibrotide (Defitelio, Gentium), and provide motivation for a general class effect from antiplatelets (note: we have no robust data to date specifically for clopidogrel, which I would speculate may be compromised in studies due to adverse pharmacokinetics across the CYP2C19 hepatic enzyme within the P450 Cytochrome system).

I should note at the onset that, although one systematic review of standard-of-care treatment for bladder cancer failed to find any significant difference in recurrence-free survival rates following antiplatelet administration1, all the component seven studies reviewed exhibited important methodological limitations, and the aggregate data to date when systematically reviewed and critically appraised contradict these findings (see below):

Preclinical Motivation and Support

First, we know that antiplatelet drugs possess antineoplastic properties in vitro in a variety of malignancy types2,3 via a time and dose-dependent apoptotic effect on cancer cells. The molecular motivation also stems in significant part the fact that tumor cell-induced platelet aggregation (called TCIPA) is a significant contributor to and enabler of hematogenous metastasis, so that pretreatment with antiplatelet therapy significantly inhibits TCIPA, helping to interrupt the cancer metastasis cascade (during hematogenous dissemination, the interaction of circulating tumor cells (CTCs) with platelets via TCIPA is believed to promote tumor cell survival within the circulation4 with considerable preclinical data in support5,6, via in part as the data shows, by inhibition of three major platelet activation pathways, glycoprotein (GP)-Ib-IX, GPIIb/IIIa, and adenosine diphosphate (ADP)7 implicated in the promotion of tumor metastases.

Human Clinical Evidence

But beyond these preclinical studies, we also have human clinical data to support a clinically relevant anticancer benefit by the addition of antiplatelet therapy. In one study that examined the impact of antiplatelet treatment on colorectal cancer staging characteristics8, it was found that the mean tumor, node and metastasis stage was 2.57 for the control group compared to 2.27 for the antiplatelet group, with the incidence of advanced disease (stage IV) being significantly lower for the antiplatelet group of the study.

Furthermore, a randomized controlled trial (RCT)9 of the influence of antiplatelet drugs on the efficacy of combined antiplatelet plus standard oncotherapy (fixed chemotherapy plus radiotherapy) of small cell lung cancer (SCLC) which evaluated objective response rates, time to remission, and patient survival found that patients on antiplatelet therapy - defibrotide (Defitelio, Gentium) or ticlopidine (Ticlid(e) - had:

(1) 100% objective response (complete response (CR) plus partial response (PR)) compared to 46.7% in the aspirin treated group, with 9.5% in patients treated with aspirin compared to 68% in group of patients treated with the antiplatelet defibrotide;

(2) average remission time varied from 27.5 weeks in the control group to 50 weeks in patients treated with defibrotide;

(3) median overall survival time was 36.5 weeks within the control group and 53 weeks in the groups treated with addition of antiplatelet therapy; thus patients treated with the combined chemotherapy + antiplatelets had 1.5 fold greater probability of survival as compared with controls, with the longest survival above 4 years observed in the group of patients treated with addition with defibrotide.

Conclusions

These human clinical studies, along with the strong molecular support found within multiple preclinical studies, collectively support the plausibility of a clinically significant anticancer benefit from antiplatelet therapies, and future studies should help clarify the most effective agents and their optimal deployment, and validate the positive benefit/harm ratio (no significant safety signals were raised in the human clinical studies, including the RCT).

References

Very Little to add, but anecdotal reports, to the review by C Kaniklidis, very good as usual. Some reports existed of an improved PFS and OS in Lung cancer patients that received heparin, an independent investigator, S Sanchez-Harguindey, in Vitoria, Spain, had experience in this, also Brugarolas, in CUN, Pamplona, Spain.

Very early publications spoke about a beneficial effect of adding Dipyridamole to conventional ChemoTherapy in metastatic ColoRectal Cancer patients, however, my info is scarce about this effect mediated by an antiplatelet action, an anti-COX action, 5-FU modulation, or an anti-MDR action.

Thanks. Salud †

Clopidogrel useful with atrial fibrillation. It may not use in cancer treatment.