Hi Arvind,

have a look at this article: http://carcin.oxfordjournals.org/content/30/3/377.abstract

This should give you a general overview.

Best,

Kai

Hi,

Check this article

https://www.researchgate.net/publication/5473153_Synthesis_and_biological_evaluation_of_novel_sulfonanilide_compounds_as_antiproliferative_agents_for_breast_cancer

Bin Su et al, published several articles about COX-2 inhibitor with anticancer activity

best regard

Article Synthesis and Biological Evaluation of Novel Sulfonanilide C...

Look at this article:

https://www.researchgate.net/publication/234142126_Cyclooxygenase-2_Generates_the_Endogenous_Mutagen_trans-4-Hydroxy-2-nonenal_in_Enterococcus_faecalis-infected_Macrophages

COX-2 inhibitors can block production of endogenous mutagens, which may be a real mechanism how COX-2 inhibitors prevent cancer.

Article Cyclooxygenase-2 Generates the Endogenous Mutagen trans-4-Hy...

Since recent research has shown a correlation between inflammation and cancer and many inflamatory mediators such as cytokines/chemokines prostaglandins etc. can influence tumor growth and progression, using anti-inflamatories makes sense as an ajunct therapy to both surgery and chemotherapy.

The contributors above (Kai Albring, Carlos Gueto, Xingmin Wang, and Peter Thomas) have provided valuable resources on some of the potential basic science and preclinical motivations and mechanisms that may underlie anticancer benefits from COX-2 inhibitors and related NSAID agents, along with some shrewd points concerning the core inflammatory basis of maligancy and progression, and the Cancer Research UK Colorectal Tumour Biology Group review that Kai Albring cited remains one of the best analyses of the vital importance of the COX–prostaglandin pathway in carcinogenesis and tumorigenesis. I will therefore here restrict my attention to the wider domain of human clinical data on this issue, but only at the level of global anticancer preventive benefit; specific malignancies in particular breast, prostate, colorectal and lung cancer, require their own separate and cancer-type-specific review and critical appraisal, beyond the scope of my brief commentary here (my findings below are only a concise summary, distilled from a longer more comprehensive review [pending)].

First, we have compelling epidemiological evidence that consumption of aspirin or other NSAIDs is inversely related to cancer risk, with relative risk reductions in ranging between 50% and 90% [1,2].

Second, there is also compelling human clinical evidence of benefit of cancer-preventive effect of COX-2 inhibitors or NSAIDs: a growing body of evidence suggests that anti-inflammatory medications, such as aspirin, NSAIDs and COX-2 selective inhibitors, have a clinically relevant chemoprotective effect in many malignancy contexts [3]. Thus one well-designed trial [4] found that regular NSAID use reduced the risk of GI cancers (OR = 0.3), with a more pronounced protective effect among those with continuous NSAID use of more than 5 years (OR = 0.2). In addition, a recent meta-analysis [5] found a significant reduction in the incidence of gastric cancer in aspirin or non-aspirin NSAID users (OR = 0.74). And more recently still, a review of RCT data [6] examined the association between NSAID use and CRC mortality among 160,143 postmenopausal women enrolled in the Women's Health Initiative (WHI), finding that NSAID use is associated with lower CRC mortality among postmenopausal women who use these medications more consistently over time.

It is clear therefore that both clinical and epidemiological data, as well as preclinical in vitro and in vivo data, collectively provide strong evidence of a clinically relevant cancer risk reductive benefit derivable from COX-2 inhibitory or NSAID agents. It now remains, I would argue, to more definitely establish:

(1) the time-duration usage as well as dosage thresholds for beneficial effects to accrue;

(2) the range, and limits, of malignancy types where benefits are evidenced (colorectal cancer providing the strongest case, with some inconsistent data in most other malignancies);

(3) the optimal therapeutic partners - when these agents are used in the treatment setting, not just the prevention setting - to these agents (endocrine, biological, or chemotherapeutic) in order to maximize outcomes; (

4) the identification, management and minimization of the potential long-term adverse effects of these agents (especially GI effects and cardiovascular impact); and

(5) finally, the extent to which we may be able to deploy less toxic, more patient-tolerable natural agent substitutes (like high-dose standardized curcuminoids) for near-comparable activity but potentially superior QoL, research that is undergoing (including my myself) as we speak.

METHODOLOGY OF THIS REVIEW

A search of the PUBMED, Cochrane Library / Cochrane Register of Controlled Trials, MEDLINE, EMBASE, AMED (Allied and Complimentary Medicine Database), CINAHL (Cumulative Index to Nursing and Allied Health Literature), PsycINFO, ISI Web of Science (WoS), BIOSIS, LILACS (Latin American and Caribbean Health Sciences Literature), ASSIA (Applied Social Sciences Index and Abstracts), SCEH (NHS Evidence Specialist Collection for Ethnicity and Health) and SCIRUS databases was conducted without language or date restrictions, and updated again current as of date of publication, with systematic reviews and meta-analyses extracted separately. Search was expanded in parallel to include just-in-time (JIT) medical feed sources as returned from Terkko (provided by the National Library of Health Sciences - Terkko at the University of Helsinki). A further "broad-spectrum" science search using SCIRUS (410+ million entry database) was then deployed for resources not otherwise included. Unpublished studies were located via contextual search, and relevant dissertations were located via NTLTD (Networked Digital Library of Theses and Dissertations) and OpenThesis. Sources in languages foreign to this reviewer were translated by language translation software.

References

1. Zimmermann, K.C., Sarbia, M., Weber, A.A., et al., 1999. Cyclooxygenase-2 expression in human esophageal carcinoma. Cancer Res. 59, 198.

2. Wilson, K.T., Fu, S., Ramanujam, K.S., et al., 1998. Increased expression of inducible nitric oxide synthase and cyclooxigenase-2 in Barrett’s esophagus and associated adenocarcinomas. Cancer Res. 58, 2929.

3. Rubio, C.A., 1986. Further studies on the therapeutic effect of indomethacin on esophageal tumors. Cancer 58, 1029..

4. Coogan, P.F., Rosenberg, L., Palmer, J.R., et al., 2000. Nonsteroidal anti-inflammatory drugs and risk of digestive cancers at sites other than the large bowel. Cancer Epidemiol. Biomarkers Prev. 9, 119– 123.

5. Abnet, C.C., Freedman, N.D., Kamangar, F., et al., 2009. Nonsteroidal anti-inflammatory drugs and risk of gastric and oesophageal adenocarcinomas: results from a cohort study and a metaanalysis. Br. J. Cancer 100, 551–557.

6. Coghill AE, Phipps AI, … Newcomb PA. The association between NSAID use and colorectal cancer mortality: results from the women's health initiative. Cancer Epidemiol Biomarkers Prev 2012; 21(11):1966-73.

Whatever, don't forget the Rofecoxib (Vioxx®) failure.