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Current application of selective COX-2 inhibitors in cancer prevention and treatment
M Suzanne Stratton1, David S Alberts
1Arizona Cancer Center, Tucson 85719, USA. msstratton@azcc.arizona.edu
Abstract:
The multistep process of carcinogenesis, which can take many years, provides many opportunities for intervention to inhibit disease progression. Effective chemoprevention agents may reduce the risk of cancer by inhibiting the initiation stage of carcinoma through induction of apoptosis or DNA repair in cells harboring mutations, or they may act to prevent promotion of tumor growth. Similarly, chemoprevention may entail blocking cancer progression to an invasive phenotype. Over the past decade, in vitro, preclinical, and clinical data have supported the hypothesis that cyclooxygenase (COX)-2 plays a central role in oncogenesis and that treatment with COX-2 inhibitors offers an effective chemoprevention strategy, as exemplified by the activity of celecoxib (Celebrex) in familial adenomatous polyposis. These COX-2 data have contributed to initiation of clinical trials testing COX-2 inhibitors for the chemoprevention of a wide variety of cancers that overexpress COX-2.
Insights
Chemoprevention strategies targeting cyclooxygenase (COX)-2 show promise in inhibiting cancer development. COX-2 inhibitors may prevent cancer initiation, promotion, and progression, offering a new avenue for cancer risk reduction.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Carcinogenesis is a multistep process offering intervention opportunities.
- Cyclooxygenase (COX)-2 is implicated in oncogenesis.
- COX-2 inhibitors are being investigated for cancer chemoprevention.
Purpose of the Study:
- To evaluate the role of COX-2 in cancer development.
- To explore the potential of COX-2 inhibitors as chemopreventive agents.
Main Methods:
- Review of in vitro, preclinical, and clinical data on COX-2 and its inhibitors.
- Analysis of celecoxib's activity in familial adenomatous polyposis.
- Initiation of clinical trials for various cancers overexpressing COX-2.
Main Results:
- Data support COX-2's central role in oncogenesis.
- COX-2 inhibitors demonstrate chemopreventive potential.
- Celecoxib shows activity in familial adenomatous polyposis.
Conclusions:
- Targeting COX-2 with inhibitors is a viable chemoprevention strategy.
- Further clinical trials are investigating COX-2 inhibitors for diverse cancers.
- COX-2 inhibitors may reduce cancer risk by blocking key stages of tumorigenesis.