Targeting cyclooxygenase-2 in hematological malignancies: rationale and promise

Curr Pharm Des. 2008;14(21):2051-60. doi: 10.2174/138161208785294654.

Abstract

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, Hodgkin's lymphoma, non-Hodgkin's 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Cyclooxygenase 2 / drug effects*
  • Cyclooxygenase 2 / metabolism
  • Cyclooxygenase 2 Inhibitors / pharmacology*
  • Cyclooxygenase 2 Inhibitors / therapeutic use
  • Drug Delivery Systems
  • Gene Expression Regulation, Neoplastic
  • Hematologic Neoplasms / drug therapy*
  • Hematologic Neoplasms / physiopathology
  • Humans

Substances

  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase 2