Chemoprevention strategies using NSAIDs and COX-2 inhibitors

Area of Science:

• Oncology
• Pharmacology
• Gastroenterology

Background:

• Non-steroidal anti-inflammatory drugs (NSAIDs) have demonstrated chemopreventive efficacy against colorectal cancer.
• NSAIDs may also reduce the incidence of various other carcinomas, including those of the esophagus, stomach, breast, lung, prostate, urinary bladder, and ovary.
• Current clinical application is primarily limited to patients with familial adenomatous polyposis (FAP), benefiting from sulindac or celecoxib.

Purpose of the Study:

• To review the molecular and clinical aspects of chemoprevention of the adenoma-carcinoma sequence using NSAIDs or COX-2 inhibitors.
• To discuss the established and potential chemopreventive roles of NSAIDs beyond colorectal cancer.
• To explore the ongoing debate regarding the mechanisms of NSAID chemoprevention and the need for further research.

Main Methods:

• Literature review of molecular and clinical studies on NSAIDs and COX-2 inhibitors in cancer chemoprevention.
• Discussion of proposed molecular targets and mechanisms underlying NSAID chemopreventive effects.
• Analysis of current limitations, resistance mechanisms, and potential for combination therapies.

Main Results:

• NSAIDs are effective in preventing colorectal cancer and show potential for other cancers.
• COX-2 inhibition is a significant, but not the sole, mechanism for NSAID chemoprevention.
• NSAID efficacy is incomplete, and resistance mechanisms require further investigation.

Conclusions:

• NSAIDs and selective COX-2 inhibitors hold promise for cancer chemoprevention, particularly for the adenoma-carcinoma sequence.
• Understanding the complex molecular mechanisms and addressing resistance are crucial for optimizing NSAID-based chemoprevention.
• Combination therapies may offer enhanced efficacy and reduced toxicity, warranting further study.