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Biomedical subjects

Ernest T Hawk

Publications and source records attributed to Ernest T Hawk.

28 records · Page 2Linked to original sources
PubMed2003

Development of COX inhibitors in cancer prevention and therapy.

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.

Animals↗
PubMed2003

Cyclooxygenase inhibition in cancer prevention and treatment.

Several lines of evidence suggest that the cyclooxygenase enzymes (specifically COX-2) might be an important molecular target for the intervention of cancer at both early and late stages of some cancers, providing an opportunity for both cancer prevention and therapy. COX-2 is overexpressed during carcinogenesis, and appears to have a role in both tumour initiation and promotion and is amenable to intervention. This review discusses the importance of COX modulation via non-specific, as well as COX-2 specific COX inhibitors (NSAIDs and COX-2 selective inhibitors [COXIB]). A brief discussion on the pharmacoeconomic considerations of NSAID and COXIB use and safety issues that have recently been the focus of debate, will be presented.

Anticarcinogenic Agents↗
PubMed2002

Chemoprevention of colorectal carcinogenesis.

The field of cancer prevention is advancing rapidly, largely owing to post-genomic technology that has revolutionized our ability to identify and characterize molecular profiles for cancer. Advances in colorectal cancer screening (e.g., endoscopy, fecal occult blood testing, and mutational analysis) have made the detection and eradication of preinvasive neoplastic lesions the standard of care. Basic and translational sciences are building on these advances, and continue to expose molecular hallmarks of carcinogenesis that can be exploited as targets for molecularly targeted preventive interventions (i.e., chemoprevention). These targets will help identify more effective and better tolerated preventive agents. Carcinogenesis is now recognized as a disease in itself and has become the target of an ever-expanding array of preventive interventions.

Adenomatous Polyposis Coli↗
PubMed2002

Epidemiology and prevention of colorectal cancer.

CRC, the second-leading cause of cancer death in the United States, is a highly preventable disease. Ironically, available and effective screening technologies are not consistently applied, even as new ones are developed. This discordance between preventive opportunity and practice conveys a sobering message regarding nontechnologic issues that must be addressed if the promise of CRC prevention is to be realized. Our response to this message will determine the public health impact of cancer prevention. In the 1980s, cancer chemoprevention was regarded as scientific speculation. Within the last decade, however, cancer has been recognized as a late, nonobligate stage of carcinogenesis, a chronic process that provides time and targets for preventive intervention. Further advances are emerging out of rigorous clinical testing, which remains the limiting factor in transforming ingenious concepts into useful tools for the prevention of CRC. The challenges and rewards of participation in chemoprevention research--both as patients and health care providers-have never been greater.

Biomarkers, Tumor↗
PubMed2002

Chemoprevention of colorectal cancer: problems, progress, and prospects.

Chemoprevention holds great promise as a complement to traditional CRC screening and treatment. Effective chemopreventive agents might improve patient outcomes by reducing the number of missed lesions, the morbidity associated with their identification and treatment, and their malignant potential. In addition, chemoprevention may reduce neoplastic potential simultaneously in several organs and improve clinical outcomes for persons at risk for cancers at multiple sites (e.g., colorectal and extracolonic cancers in HNPCC cohorts). Complex molecular circuits underlie the disease mosaic that is associated with aging. Several of these diseases share common mechanisms against which preventive interventions appear to be effective, such as NSAIDs for colorectal neoplasia and neurodegenerative disease, and statins for cardiovascular disease and colorectal neoplasia. Understanding these mechanisms and effects could raise prevention science to an entirely new level. The number of trials that are investigating chemopreventives against CR neoplasia is relatively small; if these agents live up to a fraction of their promise, the public health impact may be great (see Table 6).

Chemoprevention↗
PubMed2002

The role of cyclooxygenase inhibitors in cancer prevention.

Carcinogenesis results from the long-term accumulation of genetic and epigenetic aberrations at the molecular level, which are under constant selection pressure for growth advantage. Recognizing that cancer is the result of this long-term, multi-step process provides opportunities for molecularly targeted cancer prevention. Ideally, chemopreventive agents should be low in toxicity, morbidity, and cost. Several individual agents and agent combinations are currently under evaluation in the U.S. National Cancer Institute s (NCI) chemoprevention agent development program. Nonsteroidal anti-inflammatory drugs (NSAIDs) that inhibit cyclooxygenase (COX) -1 and -2 are among the most promising classes of agents for targeted molecular prevention.

Animals↗
PubMedDate not supplied

Mechanisms and applications of non-steroidal anti-inflammatory drugs in the chemoprevention of cancer.

Biological and chemical irritants can be the cause of irritation in a variety of organ sites. It is becoming well understood that chronic irritation in any form can initiate and accelerate the cancer process in these same organs. This understanding comes in part from the many epidemiologic studies which point out that chronic inflammation correlates with increased risk of developing cancer in that organ which is affected. One of the hallmarks of chronic irritation is the increased activity in the arachidonic acid pathway which provides many of the necessary inflammatory biochemical mediators to this process. Arachidonic acid metabolism diverges down two main pathways, the cyclooxygenase (COX) and the lipoxygenase (LOX) pathways. The COX pathway leads to prostaglandin and thromboxane production and the LOX pathway leads to the leukotrienes (LTs) and hydroxyeicosatetraenoic acids (HETEs). These classes of inflammatory molecules exert profound biological effects which enhance the development and progression of human cancers. A large number of synthetic drugs and natural products have been discovered that block many of these key pathways. Much experimental evidence in animals has shown that inhibition of the key enzymes which drive these pathways can, in fact, prevent, slow or reverse the cancer process. The data are convincing in a number of organ sites including colon, breast, lung, bladder and skin. More recently, double-blinded randomize clinical trials in humans have shown the prevention of colonic polyps by anti-inflammatory agents. These studies have primarily used non-steroidal anti-inflammatory drugs (NSAIDS) which block the COX pathways. Recent preclinical studies indicate that the LOX pathway also may be an important target for cancer prevention strategy. The expression of high levels of these enzymes in cancerous tissues make them an obvious first target for cancer prevention strategies. As newer more specific drugs are developed with few adverse effects this important prevention strategy may become a reality.

Anti-Inflammatory Agents, Non-Steroidal↗