COX-2 expression achieves its zenith at a particular stage of the cancer progression.Hence, the timing of cancer treatment to block the enzyme is vital
KATHMANDU, APRIL 4
Cyclooxygenase (COX) inhibitors are 'sophisticated' non-steroidal anti-inflammatory drugs (NSAIDs). Research 'wraps up' the idea that conventional cyclooxygenase-2 (COX-2), or coxib inhibitors, represent an advance one that provides conventional treatment with a well-defined place in clinical practice. But, what bogs down the frenzied enthusiasm is not about efficacy in isolation, or long-term, because coxibs also seem to be more than a match to classical, or traditional, non-steroidal anti-inflammatory drugs (NSAIDs) in easing acute and chronic pain, besides presenting with the prospect of 'somewhat less' serious side-effects.
The negatives aside the amount of information now available to us for arriving at a definitive conclusion in favour of conventional coxibs is approximate, albeit the fundamental facts vis-à-vis their efficiency are rather mixed, varied, or just controversial.
In addition to this, as evidence for damage continues to ascend with traditional, or conventional, NSAIDs in causing deaths,reports suggest that on an average 1 in 1,200 patients taking them for at least four weeks could die from gastro-duodenal complications.
In an editorial published in "The Journal of the American Medical Association", it was estimated that for low-risk patients for whom the hazard of developing a NSAID-related ulcer complication is 0.4 per cent, the cost of preventing a single complication was US$350,000.
It may also be emphasised that conventional NSAIDs and COX-2 inhibitors subdue renal, or kidney, activity. Research suggests that this could be accountable for certain cases of peripheral oedema (swelling) seen in clinical trials. A meta-analysis (research synthesis) on the effect of NSAIDs on post-operative kidney function reports a clinically unimportant and short-lived reduction in renal function with NSAIDs. In another study, a randomised comparison of coxib drugs, such as celebrex and indomethacin, suggested that they caused clinically inconsequential and transitory retention of sodium, but no real slump in kidney filtration rate.
This is, indeed, the fun-damental reason why researchers have designed coxibs with a definitive purpose: to crush inflammation.
But, this isn't all.
COX-2 inhibitors have emerged as lead players for preventing cancer, an inflammatory disorder; also, its recurrence. Gary J Kelloff, MD, a researcher at the National Cancer Institute, US, who lists the requirements for a molecular tar-get, such as the COX-2 enzyme, says it must be highly expressed in pre-cancer, or cancer cells, and not in others. Blocking it, he adds, isn't harmful, because it doesn't disrupt normal function. According to Makoto Taketo, MD, DMedSc, a professor of pharmacology at Japan's Kyoto University Graduate School of Medicine, these "aspirin-like NSAIDs" act pharmacologically as anti-inflammatory agents and analgesics and, in so doing, they reduce fever. Coxibsalso cause 'minimal' side-effects, unlike aspirin, which causes gastro-intestinal ulceration and bleeding.
NSAIDs weaken two forms of the coxib enzymes and, of the two it is only one, COX-1, which causes adverse effects. They also inhibit COX-2 enzymes, which are synthesised from arachidonic acid in cell membranes. In otherwords, COX-1, the 'housekeeping' variant', is expressed in several cells; it provides the basic functions of life. In contrast, COX-2, which can be, more or less, 'influenced' by means fair and square, is not made in normal epithelium or layers of cells that line hollow organs and glands. It causes inflammation and promotes tumour formation in response to growth factors, cytokines protein molecules, or communication links, between immune systemcells or oncogene, a gene that can cause a cell to develop into a tumour, or cancer.
COX-2 stimulates the production of a particular type of prostaglandins, which activates a specific epithelium receptor. This activity sets off a process for the tumour to spread.
When Taketo and his group deciphered the route to this corridor, they "knocked them out".
As a matter of fact, the first evidence that COX-2 enzymes were involved in causing DNA damage associated with cancer was provided in a University of Pennsylvania study. The finding offered a new insight into how aspirin, along with diets rich in fruits, grains and vegetables, seemed to decrease the risk of some forms of cancer. This also suggested that COX-2 inhibitor drugs may prevent DNA damage caused by COX-2 enzymes.
COX-2 expression achieves its zenith at a particular stage of the cancer pathogenesis (disease progression).
Hence, the timing of cancer treatment to block the enzyme is vital.
More importantly, cancer specialists are optimistic that COX-2 inhibitors that work well on FAP (Familial adenomatous polyposis, an inherited disorder) could help individuals who suffer from common forms of colon cancer.
In one study, Kelloff and his group of researchers measured the effects of six months of celebrex at lowor high-dose versus placebo, or dummy pill, on the duodenum in FAP patients.
When they monitored the progress, the polyp area had decreased substantially (14.5 per cent) in patients given high doses of coxibs, in comparison to placebo group (1.4 per cent). Celebrex reduced the affected locale by 31 per cent.
COX-2 inhibitors may also be effective on cancers that originate in the small intestine, aside from other types of cancer. Researchers from Hirosaki University School of Medicine in Japan, to illustrate just one study, found COX-2 production in all 26 patients they examined with Helicobacter pylori-associated intestinal-type gastric cancer, except in four patients with scattered gastric cancer.
They found that COX-2 was predominant in the pre-cancerous (metaplasia) stage. They proposedthat it would be useful to employ coxibs early enough to treat cancer.
A version of this article appears in the print on April 5, 2023, of The Himalayan Times.
