Enhancing radiotherapy with cyclooxygenase-2 enzyme inhibitors

A rational advance?

Hak Choy, Luka Milas

Research output: Contribution to journalArticle

140 Citations (Scopus)

Abstract

Results of preclinical studies suggesting that the efficacy of molecular therapies is enhanced when they are combined with radiation have generated a surge of clinical trials combining these modalities. We reviewed the literature to identify the rationale and experimental foundation supporting the use of cyclooxygenase-2 (COX-2) inhibitors with standard radiotherapy regimens in current clinical trials. Radiation affects the ability of cells to divide and proliferate and induces the expression of genes involved in signaling pathways that promote cell survival or trigger cell death. Future advances in radiotherapy will hinge on understanding mechanisms by which radiation-induced transcription of genes governs cell death and survival, the selective control of this process, and the optimal approaches to combining this knowledge with existing therapeutic modalities. COX-2 is expressed in all stages of cancer, and in several cancers its overexpression is associated with poor prognosis. Evidence from clinical and preclinical studies indicates that COX-2-derived prostaglandins participate in carcinogenesis, inflammation, immune response suppression, apoptosis inhibition, angiogenesis, and tumor cell invasion and metastasis. Clinical trial results have demonstrated that selective inhibition of COX-2 can alter the development and the progression of cancer. In animal models, selective inhibition of COX-2 activity is associated with the enhanced radiation sensitivity of tumors without appreciably increasing the effects of radiation on normal tissue, and preclinical evidence suggests that the principal mechanism of radiation potentiation through selective COX-2 inhibition is the direct increase in cellular radiation sensitivity and the direct inhibition of tumor neovascularization. Results of current early-phase studies of non-small-cell lung, esophageal, cervical, and brain cancers will determine whether therapies that combine COX-2 inhibitors and radiation will enter randomized clinical trials.

Original languageEnglish (US)
Pages (from-to)1440-1452
Number of pages13
JournalJournal of the National Cancer Institute
Volume95
Issue number19
StatePublished - Oct 1 2003

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Cyclooxygenase 2 Inhibitors
Enzyme Inhibitors
Cyclooxygenase 2
Radiotherapy
Radiation
Neoplasms
Radiation Tolerance
Clinical Trials
Cell Survival
Cell Death
Radiation Effects
Esophageal Neoplasms
Non-Small Cell Lung Carcinoma
Brain Neoplasms
Uterine Cervical Neoplasms
Prostaglandins
Carcinogenesis
Therapeutics
Randomized Controlled Trials
Animal Models

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Enhancing radiotherapy with cyclooxygenase-2 enzyme inhibitors : A rational advance? / Choy, Hak; Milas, Luka.

In: Journal of the National Cancer Institute, Vol. 95, No. 19, 01.10.2003, p. 1440-1452.

Research output: Contribution to journalArticle

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