COX Inhibitors in Cancer Prevention and Therapy

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Development of COX Inhibitors in Cancer Prevention and Therapy.Umar A, Viner JL, Anderson WF, Hawk ET.On the strength of in vitro, in vivo, observational, and clinical data, nonsteroidal antiinflammatory drugs (NSAIDs)-also referred to as COX inhibitors-have emerged as lead compounds for cancer prevention, and possible adjuncts to cancer therapy. Thus far, the routine use of NSAIDs for these indications is limited, largely owing to toxicity concerns, the paucity of efficacy data for any specific target organ, and uncertainties with regard to the most appropriate regimen (i.e., the best agent, formulation, dose, route of administration, and duration). Strategies to address these concerns primarily aim to improve the therapeutic index (i.e., benefit:risk ratio) of COX inhibitors by 1) minimizing systemic exposures whenever feasible, 2) achieving greater mechanistic specificity, 3) coadministering agents that provide prophylaxis against common toxicities, and 4) coadministering other effective anticancer agents. Clinical trials testing most of these strategies have been completed or are under way. The National Cancer Institute has a substantial research portfolio dedicated to the identification, testing, and development of NSAIDs as preventive and therapeutic anticancer agents. Discovering how to apply NSAIDs in persons with-or at risk for-cancer, although challenging, has the potential for considerable clinical and public health benefits.COX-2 Inhibitors and Cancer Therapeutics: Potential Roles for Inhibitors of COX-2 in Combination With Cytotoxic Therapy: Reports From a Symposium Held in Conjunction With the Radiation Therapy Oncology Group June 2001 Meeting.Dicker AP.Tumor growth and angiogenesis are interdependent. Cyclooxygenase (COX) catalyzes the synthesis of prostaglandins (PGs) from arachidonic acid. Nonsteroidal antiinflammatory drugs (NSAIDs) inhibit COX-mediated synthesis of PGs. Although COX-1 is constitutively expressed in a wide range of tissues, COX-2 is cytokine inducible. Enhanced COX-2 expression has been attributed a key role in the development of inflammation and related processes observed in pathologically altered disease states. Two specific COX-2 inhibitors, namely, rofecoxib (Vioxx) and celecoxib (Celebrex), both oral agents and FDA approved, have been shown preclinically and clinically to have efficacy comparable to that of NSAIDs for relief of pain and inflammation in osteoarthritis, with decreased risk of gastrointestinal damage. Significant preclinical evidence strongly supports the potential role for these inhibitors for the treatment of cancer. On June 29, 2001, the Radiation Therapy Oncology Group (www.rtog.org), a National Cancer Institute-sponsored cooperative group, held a 1-day symposium focusing on the potential role of inhibitors of COX-2 in the treatment of cancer. This issue of the American Journal of Clinical Oncology contains the summary of those presentations.J Coll Physicians Surg Pak. 2003 Jun;13(6):361-5. Related Articles, LinksRole of COX-2 specific inhibitors in oncogenesis.Gumgumji AA, Dawood T, Parvez T.Department of Gastroenterology, King Fahad Hospital, Al Madina Al Munawra, KSA.Cyclooxygenase-2 (COX-2) is over expressed in a variety of premalignant and malignant conditions. It may contribute to carcinogenesis by modulating xenobiotic metabolism, apoptosis, immune surveillance, and angiogenesis. Selective COX-2 inhibitors suppress the formation of tumors in experimental models. Selective COX-2 inhibitors also suppress the growth and metastases of established tumors and enhance the anticancer activity of both radiotherapy and chemotherapy in experimental animals. This review aims at discussing evidence that inhibition of COX-2 represents a promising strategy to treat, prevent or possibly prevent human malignancies. Importantly, selective COX-2 inhibitors do not inhibit platelet function and cause fewer gastrointestinal side effects (peptic ulcer disease) than traditional nonsteroidal anti-inflammatory drugs (NSAIDS). More clinical trials are warranted to define the role of selective COX-2 inhibitors in the prevention and treatment of cancer along with their assessment of toxicity.