NSAIDS, COXIBS, CLOXIBS and cancer pain

Abstract

Cancer pain is the major cause of suffering in more than two thirds of cancer patients. Cancer pain affects quality of life and mental health status of majority of these patients and therapeutic intervention is often essential to give relief to cancer patients. Chronic inflammation can promote cancer and cancer in turn induces Inflammation. Cyclooxygenase (COX) and lipoxygenase (LOX) pathways are critical components of inflammation. Cyclooxygenases are lipid dioxygenases that oxygenate polyunsaturated fatty acids like arachidonic acid to give rise to 'hormone like' fatty acid derivatives such as prostaglandins, which mediate inflammation and pain. COX-2 derived prostaglandins are the principal mediators of inflammation and pain in pathological conditions and dramatic up-regulation of COX-2 was observed in premalignant and malignant conditions of various cancers. COX-2 is also up-regulated in several cancers such as breast, prostate and lung that metastasize to bone and bone pain is one of the severe forms of cancer pain in majority of the cancer patients. Non-steroidal anti-inflammatory drugs (NSAIDs) are the front line of therapeutic options for alleviating variety of pains, including cancer pain. The first generation NSAIDs are non-selective in nature and inhibit both COX-1 and COX-2 leading to gastrointestinal side effects. The COX-2 selective NSAIDs (COXIBS), on the other hand, have shown promise in clinical trials to inhibit cancer and cancer pain without gastric side effects. However, long-term administration of COXIBs resulted in cardiovascular complications emphasizing the need to develop safer inhibitors of COX-2 to treat inflammation and cancer pain. In this connection, COX-2/5-LOX dual inhibitors (CLOXIBs) such as Licofelone and Curcumin appear promising with the potential to alleviate cancer pain with minimum or no side effects. © 2011 Nova Science Publishers, Inc.