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Prostaglandins have long been known to impact the radiosensitivity of cells and tissues, and many studies have centered on exploiting nonspecific prostaglandin inhibitors such as NSAIDs for therapeutic gain. These studies have ultimately been unsuccessful due to the lack of targeted specificity against the tumor. The discovery of the inducible cyclooxygenase enzyme (COX-2) and development of some highly selective inhibitors (which spare the constitutive COX-1 activity) has renewed excitement for modulating tumor prostaglandins as a method of specific radiosensitization of tumors, while sparing normal tissues. This review discusses these new data and generates a rationale for use of COX-2 inhibitors as radiosensitizing agents in cancer therapy.

The spontaneous metastatic properties of six sarcomas and seven carcinomas syngeneic to C3Hf/Kam mice were investigated and the correlation between spontaneous metastasis, the lung colony forming efficiency (LCFE) of i.v. injected tumor cells, and s.c. tumor take was determined. The incidence and number of spontaneous metastases in the lung were determined in mice that had primary tumors in the leg removed 17 to 120 days earlier, depending on tumor type. There was a significant positive correlation between spontaneous metastasis and LCFE when all 13 tumors were compared, but the significance was lost when carcinomas and sarcomas were considered separately. No significant correlation between spontaneous metastasis and the s.c. tumor take was observed. Also, no correlation was found between LCFE and the s.c. tumor take of carcinomas, but there was a strong inverse relationship between these two properties of sarcomas. The number of cells shed from primary tumors was estimated and found to be more extensive in tumors with higher metastatic properties. Thus, in general, highly metastatic tumors were characterized by a high LCFE and a significant cell shedding. Furthermore, LCFE was greatly increased by treatment of animals with cyclophosphamide and by admixing heavily irradiated tumor cells to viable cells, implying that local environmental factors are important in determining the establishment of tumor cell clonogens into metastasis.

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