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Celecoxib, sold under the brand name Celebrex among others, is a COX-2 inhibitor and nonsteroidal anti-inflammatory drug (NSAID).<ref name=AHFS2019>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> It is used to treat the pain and inflammation in osteoarthritis, acute pain in adults, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, painful menstruation, and juvenile rheumatoid arthritis.<ref name=AHFS2019/> It may also be used to decrease the risk of colorectal adenomas in people with familial adenomatous polyposis.<ref name=AHFS2019/> It is taken by mouth.<ref name=AHFS2019/> Benefits are typically seen within an hour.<ref name=AHFS2019/>
Common side effects include abdominal pain, nausea, and diarrhea.<ref name=AHFS2019/> Serious side effects may include heart attacks, strokes, gastrointestinal perforation, gastrointestinal bleeding, kidney failure, and anaphylaxis.<ref name=Coxib2013/><ref name=AHFS2019/> Use is not recommended in people at high risk for heart disease.<ref name=AHA2007>Template:Cite journal</ref><ref name=Consumer2012>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> The risks are similar to other NSAIDs, such as ibuprofen and naproxen.<ref name=NPR2018>Template:Cite news</ref> Use in the later part of pregnancy or during breastfeeding is not recommended.<ref name=AHFS2019/><ref name="Drugs.com pregnancy" />
Celecoxib has demonstrated adjunctive benefits in major depression and efficacy in reducing polyp recurrence in familial adenomatous polyposis, while also being investigated for broader psychiatric, anticancer, and chemopreventive applications.
Celecoxib was patented in 1993 and came into medical use in 1999.<ref name=Fis2006>Template:Cite book</ref> It is available as a generic medication.<ref name=BNF76>Template:Cite book</ref> In 2022, it was the 93rd most commonly prescribed medication in the United States, with more than 7Template:Nbspmillion prescriptions.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>
Medical usesEdit
Celecoxib is indicated for the treatment of osteoarthritis, rheumatoid arthritis, psoriatic arthritis, acute pain, musculoskeletal pain, painful menstruation, ankylosing spondylitis, juvenile rheumatoid arthritis, and to reduce the number of colon and rectal polyps in people with familial adenomatous polyposis.<ref name=AHFS2019/> It may be used in children with juvenile rheumatoid arthritis who are older than two years of age and weigh more than 10 kg (22 lb).<ref name=AHFS2019/>
For postoperative pain, it is more or less equal to ibuprofen.<ref>Template:Cite journal</ref> For pain relief, it is similar to paracetamol (acetaminophen) at 3990 mg per day,<ref name="Yelland">Template:Cite journal</ref> which is the first line treatment for osteoarthritis.<ref name=OARSI2007>Template:Cite journal</ref><ref>Template:Cite journal</ref>
Evidence of effects is not clear as several studies done by the manufacturer have not been released for independent analysis.<ref>Template:Cite journal</ref>
Familial adenomatous polyposisEdit
It has been used to reduce colon and rectal polyps in people with familial adenomatous polyposis, but it is not known if it decreases rates of cancer,<ref name=AHFS2019/> so it is not a good choice for this reason.<ref name=AHFS2019/>
Adverse effectsEdit
- Cardiovascular events: NSAIDs are associated with an increased risk of serious (and potentially fatal) adverse cardiovascular thrombotic events, including myocardial infarction and stroke. Risk may be increased with duration of use or pre-existing cardiovascular risk factors or disease. Individual cardiovascular risk profiles should be evaluated before prescribing. New-onset hypertension or exacerbation of hypertension may occur (NSAIDs may impair response to thiazide or loop diuretics), and may contribute to cardiovascular events; monitor blood pressure and use with caution in patients with hypertension. Celecoxib may cause sodium and fluid retention, so its use in patients with edema or heart failure warrants caution. Long-term cardiovascular risk in children has not been evaluated. Use the lowest effective dose for the shortest duration of time, consistent with individual patient goals, to reduce the risk of cardiovascular events; alternative therapies should be considered for patients at high risk.<ref>Template:Cite journal</ref> The increased risk is about 37%.<ref name=Coxib2013/>
- Gastrointestinal events: NSAIDs may increase the risk of serious gastrointestinal (GI) ulceration, bleeding, and perforation (may be fatal). These events may occur at any time during therapy and without warning. Use caution with a history of GI disease (bleeding or ulcers), concurrent therapy with aspirin, anticoagulants and/or corticosteroids, smoking, use of alcohol, and the elderly or debilitated patients. Use the lowest effective dose for the shortest duration of time, consistent with individual patient goals, to reduce the risk of GI adverse events; alternate therapies should be considered for patients at high risk. When used concomitantly with ≤325 mg of aspirin, a substantial increase in the risk of gastrointestinal complications (e.g., ulcer) occurs; concomitant gastroprotective therapy (e.g., proton pump inhibitors) is recommended.<ref name="Celebrex FDA label">{{#invoke:citation/CS1|citation
|CitationClass=web }}</ref> The increased risk is about 81%.<ref name=Coxib2013/>
- Hematologic effects: Anemia may occur; monitor hemoglobin or hematocrit in people on long-term treatment. Celecoxib does not usually affect prothrombin time, partial thromboplastin time, or platelet counts; it does not inhibit platelet aggregation at approved doses.
People with a prior history of ulcer disease or GI bleeding require special precautions. Moderate to severe liver impairment or GI toxicity can occur with or without warning symptoms in people treated with NSAIDs.
In October 2020, the U.S. Food and Drug Administration (FDA) required the drug label to be updated for all nonsteroidal anti-inflammatory medications to describe the risk of kidney problems in unborn babies that result in low amniotic fluid.<ref name="FDA PR 20201015" /><ref name="FDA safety 20201015" /> They recommend avoiding NSAIDs in pregnant women at 20 weeks or later in pregnancy.<ref name="FDA PR 20201015">Template:Cite press release Template:PD-notice</ref><ref name="FDA safety 20201015">{{#invoke:citation/CS1|citation |CitationClass=web }} Template:PD-notice</ref>
AllergyEdit
Celecoxib contains a sulfonamide moiety and may cause allergic reactions in those allergic to other sulfonamide-containing drugs. This is in addition to the contraindication in people with severe allergies to other NSAIDs. However, it has a low (reportedly 4%) chance of inducing cutaneous reactions among persons who have a history of such reactions to aspirin or nonselective NSAIDs. NSAIDs may cause serious skin adverse events, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis; events may occur without warning and in patients without prior known sulfa allergy. Use should be discontinued at the first sign of rash (or any other hypersensitivity).
Heart attack and strokeEdit
A 2013 meta-analysis of hundreds of clinical trials found that coxibs (the class of drugs that includes celecoxib) increase the risk of major cardiovascular problems by about 37% over placebo.<ref name=Coxib2013>Template:Cite journal</ref> In 2016, a randomized trial provided strong evidence that treatment with celecoxib is not more likely to result in poor cardiovascular outcomes than treatment with naproxen or ibuprofen.<ref name="NissenYeomans2016">Template:Cite journal</ref> As a result, in 2018 an FDA advisory panel concluded that celecoxib poses no greater risk for causing heart attacks and strokes than the commonly-used NSAIDs ibuprofen or naproxen and recommended that the FDA consider changing its advice to physicians regarding celecoxib's safety.<ref name=NPR2018/>
The COX-2 inhibitor rofecoxib (Vioxx) was removed from the market in 2004 due to its risk. Like all NSAIDs on the US market, celecoxib carries an FDA-mandated "black box warning" for cardiovascular and gastrointestinal risk. In February 2007, the American Heart Association warned that with respect to "patients with a prior history of or at high risk for cardiovascular disease... use of COX-2 inhibitors for pain relief should be limited to patients for whom there are no appropriate alternatives, and then, only in the lowest dose and for the shortest duration necessary."<ref name="AHA2007"/>
In 2005, a study published in the Annals of Internal Medicine found that cardiovascular effects of COX-2 inhibitors differ, depending on the drug.<ref name="pmid15684203">Template:Cite journal</ref> Other COX-2-selective inhibitors, such as rofecoxib, have significantly higher myocardial infarction rates than celecoxib.<ref name="pmid11509060">Template:Cite journal</ref> In April 2005, after an extensive review of data, the FDA concluded it was likely "that there is a 'class effect' for increased CV risk for all NSAIDs".<ref name="Jenkins">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> In a 2006 meta-analysis of randomized control studies, the cerebrovascular events associated with COX-2 inhibitors were examined, but no significant risks were found when compared to nonselective NSAIDs or placebos.<ref name="pmid17176361">Template:Cite journal</ref>
Drug interactionsEdit
Celecoxib undergoes metabolism primarily by the enzymes CYP2C9 and CYP3A4, but it also interacts with CYP2D6, inhibiting its activity without being metabolized by it.<ref name="Shkundin_2025">Template:Cite journal</ref> The CYP2C9 gene exhibits considerable genetic variability, with common polymorphisms, such as rs1799853 and rs1057910, linked to reduced enzyme activity and altered pharmacokinetics of celecoxib.<ref name="Shkundin_2025"/> Additionally, the influence of CYP2D6 on celecoxib metabolism is inconsistent, with its effect varying depending on the individual’s CYP2C9 genetic profile.<ref name="Shkundin_2025"/>
Caution must be exercised with concomitant use of 2C9 inhibitors, such as fluconazole, which can greatly elevate celecoxib serum levels.<ref name="Celebrex FDA label"/> If used concomitantly with lithium, celecoxib increases lithium plasma levels.<ref name="Celebrex FDA label"/> If used concomitantly with warfarin, celecoxib may result in an increased risk of bleeding complications.<ref name="Celebrex FDA label"/> The risk of bleeding and gastric ulcers also increases further when selective serotonin reuptake inhibitors (SSRI) are used in combination with celecoxib.<ref>Template:Cite journal</ref> The drug may increase the risk of kidney failure with angiotensin-converting enzyme-inhibitors, such as lisinopril, and diuretics, such as hydrochlorothiazide.<ref name="Celebrex FDA label"/>
Mechanism of actionEdit
Anti-inflammatoryEdit
A highly selective reversible inhibitor of the COX-2 isoform of cyclooxygenase, celecoxib inhibits the transformation of arachidonic acid to prostaglandin precursors. Therefore, it has analgesic and anti-inflammatory properties.<ref name="Celebrex FDA label"/> Nonselective NSAIDs (such as aspirin, naproxen, and ibuprofen) inhibit both COX-1 and COX-2. Inhibition of COX-1 (which celecoxib does not inhibit at therapeutic concentrations) inhibits the production of prostaglandins and the production of thromboxane A2, a platelet activator.<ref name="Celebrex FDA label"/> COX-1 is traditionally defined as a constitutively expressed "housekeeping" enzyme and plays a role in the protection of the gastrointestinal mucosa, kidney hemodynamics, and platelet thrombogenesis.<ref name=Mathew>Template:Cite journal</ref><ref name="Katzung">Template:Cite book</ref> COX-2, on the contrary, is extensively expressed in cells involved in inflammation and is upregulated by bacterial lipopolysaccharides, cytokines, growth factors, and tumor promoters.<ref name=Mathew/><ref name="Shi S and Koltz U">Template:Cite journal</ref> Celecoxib is approximately 10-20 times more selective for COX-2 inhibition over COX-1.<ref name="Katzung"/><ref>Template:Cite journal</ref> It binds with its polar sulfonamide side chain to a hydrophilic side pocket region close to the active COX-2 binding site.<ref name="DiPiro_2008">Template:Cite book</ref> In theory, this selectivity allows celecoxib and other COX-2 inhibitors to reduce inflammation (and pain) while minimizing gastrointestinal adverse drug reactions (e.g. stomach ulcers) that are common with nonselective NSAIDs.<ref>Template:Cite journal</ref>
Anti-cancerEdit
For its use in reducing colon polyps, celecoxib affects genes and pathways involved in inflammation and malignant transformation in tumors, but not normal tissues.<ref>Template:Cite journal</ref>
Celecoxib binds to Cadherin-11 (which may explain the reduction in cancer progression).Template:Citation needed
Structure-activity relationshipEdit
The Searle research group found the two appropriately substituted aromatic rings must reside on adjacent positions about the central ring for adequate COX-2 inhibition. Various modifications can be made to the 1,5-diarylpyrazole moiety to deduce the structure-activity relationship of celecoxib.<ref name="Penning">Template:Cite journal</ref> A para-sulfamoylphenyl at position 1 of the pyrazole was found to have a higher potency for COX-2 selective inhibition than a para-methoxyphenyl (see structures 1 and 2, below). In addition, a 4-(methylsulfonyl)phenyl or 4-sulfamoylphenyl is known to be necessary for COX-2 inhibition. For instance, replacing either of these entities with a –SO2NHCH3 substituent diminishes COX-2 inhibitory activity as noted with a very high inhibitory concentration-50 (see structures 3 – 5). At the 3-position of the pyrazole, a trifluoromethyl or difluoromethyl provides superior selectivity and potency compared to a fluoromethyl or methyl substitution (see structures 6 – 9).<ref name="Penning"/>
Celecoxib is compound 22; the 4-sulfamoylphenyl on the 1-pyrazol substituent is required for COX-2 inhibition and the 4-methyl on the 5-pyrazol system has low steric hindrance to maximising potency, while the 3-trifluoromethyl group provides superior selectivity and potency.<ref name="Penning" /> To explain the selectivity of celecoxib, it is necessary to analyze the free energy of binding difference between the drug molecule and COX-1 compared to COX-2 enzymes. The structural modifications highlight the importance of binding to residue 523 in the side binding pocket of the cyclooxygenase enzyme, which is an isoleucine in COX-1 and a valine in COX-2.<ref name="Price">Template:Cite journal</ref> This mutation appears to contribute to COX-2 selectivity by creating steric hindrance between the sulfonamide oxygen and the methyl group of Ile523 that effectively destabilizes the celecoxib-COX-1 complex.<ref name="Price"/>
HistoryEdit
It was initially marketed by Pfizer for arthritis. Celecoxib and other COX-2 selective inhibitors, valdecoxib, parecoxib, and mavacoxib, were discovered by a team at the Searle division of Monsanto led by John Talley.<ref name=Forbes2003>Template:Cite news</ref><ref name=SLACS>Template:Cite journal</ref>
Two lawsuits arose over the discovery of celecoxib. Daniel L. Simmons of Brigham Young University (BYU) discovered the COX-2 enzyme in 1988,<ref name="ScientistBYULitig">{{#invoke:citation/CS1|citation
|CitationClass=web
}}</ref> and in 1991, BYU entered into a collaboration with Monsanto to develop drugs to inhibit it. Monsanto's pharmaceutical division was later purchased by Pfizer, and in 2006, BYU sued Pfizer for breach of contract, claiming Pfizer did not properly pay contractual royalties back to BYU.<ref name="Deseret News">{{#invoke:citation/CS1|citation
|CitationClass=web
}}</ref> A settlement was reached in April 2012, in which Pfizer agreed to pay $450 million.<ref name="Settlement">Template:Cite news</ref><ref>Template:Cite news</ref> Other important discoveries in COX-2 were made at University of Rochester, which patented the discoveries.<ref>{{#if: 6048850
|[{{#ifeq:|uspto|http://patft.uspto.gov/netacgi/nph-Parser?patentnumber=%7Chttps://patents.google.com/patent/US}}{{#iferror:{{#expr:6048850 }}|6048850}} U.S. patent {{#ifeq:Template:Replace|Template:Digits|Template:Replace| 6048850}}]
|{{US patent|123456|link text}}
}}</ref> When the patent was issued, the university sued Searle (later Pfizer) in a case called, University of Rochester v. G.D. Searle & Co., 358 F.3d 916 (Fed. Cir. 2004). The court ruled in favor of Searle in 2004, holding in essence that the university had claimed a method requiring, yet provided no written description of, a compound that could inhibit COX-2, and therefore the patent was invalid.<ref name="hodgsonruss">{{#invoke:citation/CS1|citation
|CitationClass=web
}}</ref><ref name="kayescholer">Ranjana Kadle (2004) CAFC Court Decision Reach-Through Claims Declared Invalid</ref>
According to the National Academy of Sciences, Philip Needleman, who was vice president of Monsanto in 1989 and president of Searle in 1993<ref name="NASO" /> oversaw research into COX-2 that led to the development of the anti-inflammatory drug celecoxib (Celebrex).<ref name="NASO" /> He became senior executive vice president and chief scientist of Pharmacia from 2000 to 2003.<ref name="NASO">{{#invoke:citation/CS1|citation
|CitationClass=web
}}</ref> Celecoxib was discovered and<ref>{{#if: 5466823
|[{{#ifeq:|uspto|http://patft.uspto.gov/netacgi/nph-Parser?patentnumber=%7Chttps://patents.google.com/patent/US}}{{#iferror:{{#expr:5466823 }}|5466823}} U.S. patent {{#ifeq:Template:Replace|Template:Digits|Template:Replace| 5466823}}]
|{{US patent|123456|link text}}
}}</ref> developed by G. D. Searle & Company and was approved by the FDA on 31 December 1998.<ref>{{#invoke:citation/CS1|citation
|CitationClass=web
}}</ref> It was co-promoted by Monsanto Company (parent company of Searle) and Pfizer under the brand name Celebrex. Monsanto merged with Pharmacia, from which the Medical Research Division was acquired by Pfizer, giving Pfizer ownership of Celebrex. The drug was at the core of a major patent dispute that was resolved in Searle's favor (later Pfizer) in 2004.<ref name="hodgsonruss" /><ref name="kayescholer" /> In University of Rochester v. G.D. Searle & Co., 358 F.3d 916 (Fed. Cir. 2004), the University of Rochester claimed that United States Pat. No. 6,048,850 (which claimed a method of inhibiting COX-2 in humans using a compound, without actually disclosing what that compound might be) covered drugs such as celecoxib. The court ruled in favor of Searle, holding in essence that the university had claimed a method requiring, yet provided no written description of, a compound that could inhibit COX-2, and therefore the patent was invalid.
After the withdrawal of rofecoxib from the market in September 2004, celecoxib enjoyed a robust increase in sales. However, the results of the APC trial in December of that year raised concerns that Celebrex might carry risks similar to those of rofecoxib, and Pfizer announced a moratorium on direct-to-consumer advertising of Celebrex soon afterward. Sales reached $2 billion in 2006.<ref name="AHA2007"/> Before its availability in generic form, it was one of Pfizer's "best-selling drugs, amounting to more than $2.5 billion in sales [by 2012], and was prescribed to 2.4 million" people in 2011.<ref name=NYT2012 /> By 2012, 33 million Americans had taken celecoxib.<ref name=NYT2012>Template:Cite news</ref>
Pfizer resumed advertising Celebrex in magazines in 2006,<ref name="Berenson">Template:Cite news</ref> and resumed television advertising in April 2007 with an unorthodox, Template:Frac-minute advertisement which extensively discussed the adverse effects of Celebrex in comparison with other anti-inflammatory drugs. The ad drew criticism from the consumer advocacy group Public Citizen, which called the ad's comparisons misleading.<ref name="Saul">Template:Cite news</ref> Pfizer responded to Public Citizen's concerns with assurances that they are truthfully advertising the risk and benefits of Celebrex as set forth by the FDA.<ref name="Saul"/>
In 2025, Australian Therapeutic Goods Administration decided to include celecoxib 200mg as the first Schedule 3 (Pharmacist Only Medicine) selective COX-2 inhibitor in a primary pack containing not more than 10 dosage units for the short-term treatment of acute pain due to primary dysmenorrhoea or musculoskeletal or soft tissue injury in adults.<ref name=psa/>
Society and cultureEdit
Fabricated efficacy studiesEdit
Pfizer and its partner, Pharmacia presented findings from their study that Celebrex was "better in protecting the stomach from serious complications than other drugs."<ref name=NYT2012 /> This became Celebrex's main selling point. However, following federal investigations it was revealed that Pfizer and Pharmacia "only presented the results from the first six months of a year-long study rather than the whole thing." These partial results were then published in The Journal of the American Medical Association.<ref name=NYT2012 /> In 2001, the US Food and Drug Administration (FDA) released the full results of the Pfizer and Pharmacia study which showed that they had withheld crucial data.<ref name=NYT2012 /> By 2012, a federal judge unsealed "thousands of pages of internal documents and depositions" in a "long-running securities fraud case against Pfizer."<ref name=NYT2012 />
In March 2009, Scott S. Reuben, former chief of acute pain at Baystate Medical Center, Springfield, Massachusetts, revealed that the data for 21 studies he had authored for the efficacy of the drug (along with others such as Vioxx) had been fabricated. The analgesic effects of the drugs had been exaggerated. Reuben was also a former paid spokesperson for Pfizer. Although from 2002 to 2007 Pfizer underwrote much of Dr. Reuben's research and "many of his trials found that Celebrex and Lyrica, Pfizer drugs, were effective against postoperative pain," Pfizer was not aware of the fraudulent data.<ref name="nyt0311">Template:Cite news</ref>Template:Failed verification None of the retracted studies were submitted to either the US Food and Drug Administration or the European Union's regulatory agencies before the drug's approval. Although Pfizer issued a public statement declaring, "It is very disappointing to learn about Dr. Scott Reuben's alleged actions. When we decided to support Dr. Reuben's research, he worked for a credible academic medical center and appeared to be a reputable investigator",<ref name="WSJ-3-2009">Template:Cite news</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> the documents unsealed in 2012, revealed that by February 2000, Pharmacia employees had devised a strategy to present the findings.<ref name=NYT2012 />
Brand namesEdit
Pfizer markets celecoxib under the brand name Celebrex, and it is available as oral capsules containing 50, 100, 200, or 400 mg of celecoxib.<ref name="Celebrex FDA label" />
It is legally available in many jurisdictions as a generic under several brand names.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> In the US, celecoxib was covered by three patents, two of which expired on 30 May 2014, and one of which (US RE44048<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>) was due to expire 2 December 2015. On 13 March 2014, that patent was found to be invalid for double patenting.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Upon the patent expiry on 30 May 2014, the FDA approved the first versions of generic celecoxib.<ref>Template:Cite press release</ref>
In the US, Celebrex is marketed by Viatris after Upjohn was spun off from Pfizer.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>
ResearchEdit
PsychiatryEdit
On the theory that inflammation plays a role in the pathogenesis of major mental disorders, celecoxib has been trialed for a number of psychiatric disorders, including major depression, bipolar disorder, and schizophrenia.<ref name="repurposed2021">Template:Cite journal</ref><ref>Template:Cite journal</ref><ref name=":0">Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> A 2014 meta-analysis concluded that adjunctive treatment with celecoxib improved depressive symptoms, response, and remission rates compared to placebo.<ref name=":0" />
Bipolar disorderEdit
A meta-analysis considering trials of celecoxib as an adjunctive treatment in bipolar disorder was inconclusive citing low evidence quality.<ref name="repurposed2021"/>
Familial adenomatous polyposisEdit
It has been used to reduce colon and rectal polyps in people with familial adenomatous polyposis, but it is not known if it decreases rates of cancer,<ref name=AHFS2019/> so it is not a good choice for this reason.<ref name=AHFS2019/>
Cancer preventionEdit
The use of celecoxib to reduce the risk of colorectal cancer has been investigated, but neither celecoxib nor any other drug is indicated for this use.<ref>Template:Cite journal</ref> Small-scale clinical trials in very high-risk people (belonging to FAP families) showed celecoxib can prevent polyp growth. Hence, large-scale randomized clinical trials were undertaken.<ref name="Bertagnolli">Template:Cite journal</ref> Results show a 33 to 45% polyp recurrence reduction in people treated with celecoxib each day. However, serious cardiovascular events were significantly more frequent in the celecoxib-treated groups. Aspirin shows a similar (and possibly larger) protective effect,<ref name="Baron">Template:Cite journal</ref><ref name="Sandler">Template:Cite journal</ref><ref name="Bosetti">Template:Cite journal</ref> has demonstrated cardioprotective effects and is significantly cheaper, but no head-to-head clinical trials have compared the two drugs.
Cancer treatmentEdit
Different from cancer prevention, cancer treatment is focused on the therapy of tumors that have already formed and have established themselves inside the patient. Many studies are going on to determine whether celecoxib might be useful for this latter condition.<ref name="Dannenberg">Template:Cite journal</ref> However, during molecular studies in the laboratory, it became apparent that celecoxib could interact with other intracellular components besides its most famous target, COX-2. The discovery of these additional targets has generated much controversy, and the initial assumption that celecoxib reduces tumor growth primarily by the inhibition of COX-2 became contentious.<ref>Template:Cite journal</ref>
Certainly, the inhibition of COX-2 is paramount for the anti-inflammatory and analgesic function of celecoxib. However, whether inhibition of COX-2 also plays a dominant role in this drug's anticancer effects is unclear. For example, a recent study with malignant tumor cells showed celecoxib could inhibit the growth of these cells in vitro, but COX-2 played no role in this outcome; even more strikingly, the anticancer effects of celecoxib were also obtained with the use of cancer cell types that do not even contain COX-2.<ref name="Chuang">Template:Cite journal</ref> Karen Seibert and colleagues have published research showing antiangiogenic and antitumor activity of celecoxib in animal models.<ref>Template:Cite journal</ref>
Additional support for the idea that other targets besides COX-2 are important for celecoxib's anticancer effects has come from studies with chemically modified versions of celecoxib. Several dozen analogs of celecoxib were generated with small alterations in their chemical structures.<ref name="zhu">Template:Cite journal</ref> Some of these analogs retained COX-2 inhibitory activity, whereas many others did not. However, when the ability of all these compounds to kill tumor cells in cell culture was investigated, the antitumor potency did not at all depend on whether or not the respective compound could inhibit COX-2, showing the inhibition of COX-2 was not required for the anticancer effects.<ref name="zhu"/><ref name="Schönthal-analogs">Template:Cite journal</ref> One of these compounds, 2,5-dimethyl-celecoxib, which entirely lacks the ability to inhibit COX-2, actually displayed stronger anticancer activity than celecoxib.<ref name="Schönthal-antitumor">Template:Cite journal</ref>
ReferencesEdit
Further readingEdit
External linksEdit
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