Mechanisms of disease: Inflammatory mediators and cancer prevention

Jason R. Mann, Michael G. Backlund, Raymond N. DuBois

    Research output: Contribution to journalReview articlepeer-review

    133 Scopus citations

    Abstract

    Discovery of molecular pathways critical to carcinogenesis is revolutionizing the treatment and prevention of cancer. Traditional chemotherapeutic approaches usually cause'global'cytotoxicity to both normal and carcinoma cells. Over the past decade, however, investigators have developed compounds that inhibit tumor formation more selectively by targeting specific signaling pathways, including those involving the epidermal growth factor receptor (EGFR) and cyclooxygenase 2 (COX2). COX2-derived bioactive lipids, including prostaglandin E2, are potent inflammatory mediators that promote tumor growth and metastasis through stimulation of cell proliferation, invasion, and angiogenesis. Recent work has demonstrated significant crosstalk between the COX2 and EGFR pathways, while prechnical data demonstrates a synergistic effect when both pathways are targeted simultaneously. Combination therapy, a common strategy in cancer treatment, is likely to improve outcomes in cancer prevention as well. Ongoing clinical trials designed to assess whether low doses of COX2 and EGFR inhibitors used in combination could prove more effective and result in reduced toxicity than either agent alone may provide new options for cancer prevention and treatment. We discuss advances in cancer prevention by focusing on mechanisms by which bioactive lipids contribute to tumor formation. While cancer chemoprevention is a relatively young field, we argue that this approach to malignant disease bears significant potential.

    Original languageEnglish (US)
    Pages (from-to)202-210
    Number of pages9
    JournalNature Clinical Practice Oncology
    Volume2
    Issue number4
    DOIs
    StatePublished - Apr 2005

    Keywords

    • 15-PGDH
    • Cancer
    • Chemoprevention
    • Cyclooxygenase 2
    • Prostaglandins

    ASJC Scopus subject areas

    • Oncology

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