Nonsteroidal anti-inflammatory drugs as anticancer agents: mechanistic, pharmacologic, and clinical issues

Michael J Thun, S Jane Henley, Carlo Patrono

Risultato della ricerca: Contributo in rivistaArticolo in rivista

1226 Citazioni (Scopus)

Abstract

Numerous experimental, epidemiologic, and clinical studies suggest that nonsteroidal anti-inflammatory drugs (NSAIDs), particularly the highly selective cyclooxygenase (COX)-2 inhibitors, have promise as anticancer agents. NSAIDs restore normal apoptosis in human adenomatous colorectal polyps and in various cancer cell lines that have lost adenomatous polyposis coli gene function. NSAIDs also inhibit angiogenesis in cell culture and rodent models of angiogenesis. Many epidemiologic studies have found that long-term use of NSAIDs is associated with a lower risk of colorectal cancer, adenomatous polyps, and, to some extent, other cancers. Two NSAIDs, sulindac and celecoxib, have been found to inhibit the growth of adenomatous polyps and cause regression of existing polyps in randomized trials of patients with familial adenomatous polyposis (FAP). However, unresolved questions about the safety, efficacy, optimal treatment regimen, and mechanism of action of NSAIDs currently limit their clinical application to the prevention of polyposis in FAP patients. Moreover, the development of safe and effective drugs for chemoprevention is complicated by the potential of even rare, serious toxicity to offset the benefit of treatment, particularly when the drug is administered to healthy people who have low annual risk of developing the disease for which treatment is intended. This review considers generic approaches to improve the balance between benefits and risks associated with the use of NSAIDs in chemoprevention. We critically examine the published experimental, clinical, and epidemiologic literature on NSAIDs and cancer, especially that regarding colorectal cancer, and identify strategies to overcome the various logistic and scientific barriers that impede clinical trials of NSAIDs for cancer prevention. Finally, we suggest research opportunities that may help to accelerate the future clinical application of NSAIDs for cancer prevention or treatment.
Lingua originaleEnglish
pagine (da-a)252-262
Numero di pagine11
RivistaJournal of the National Cancer Institute
Volume94
Stato di pubblicazionePubblicato - 2002
Pubblicato esternamente

Keywords

  • Adenomatous Polyposis Coli
  • Angiogenesis Inhibitors
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal
  • Anticarcinogenic Agents
  • Antineoplastic Agents
  • Apoptosis
  • Aspirin
  • Clinical Trials as Topic
  • Colorectal Neoplasms
  • Humans

Fingerprint

Entra nei temi di ricerca di 'Nonsteroidal anti-inflammatory drugs as anticancer agents: mechanistic, pharmacologic, and clinical issues'. Insieme formano una fingerprint unica.

Cita questo