Targeting Cyclooxygenase-2 in Hematological Malignancies: Rationale and Promise
M. P. Bernard, S. Bancos, P. J. Sime and R. P. Phipps
Affiliation: Box 850, MRBX 3-11001,Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Rochester, NY 14642,USA.
Keywords: cyclooxygenase-2 (Cox-2), inflammation, hematological malignancies, chronic lymphocytic, leukemia, chronic myeloid leukemia, Hodgkin's lymphoma, multiple myeloma, anti-tumor immunity, angiogenesis
There is much interest in the potential use of Cox-2 selective inhibitors in combination with other cancer therapeutics. Malignancies of hematopoietic and non-hematopoietic origin often have increased expression of cyclooxygenase- 2 (Cox-2), a key modulator of inflammation. For example, hematological malignancies such as chronic lymphocytic leukemia, chronic myeloid leukemia, Hodgkins lymphoma, non-Hodgkins lymphoma and multiple myeloma often highly express Cox-2, which correlates with poor patient prognosis. Expression of Cox-2 enhances survival and proliferation of malignant cells, while negatively influencing anti-tumor immunity. Hematological malignancies expressing elevated levels of Cox-2 potentially avoid immune responses by producing factors that enhance angiogenesis and metastasis. Cellular immune responses regulated by natural killer cells, cytotoxic T lymphocytes, and T regulatory cells are also influenced by Cox-2 expression. Therefore, Cox-2 selective inhibitors have promising therapeutic potential in patients suffering from certain hematological malignancies.
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