[Frontiers in Bioscience 2, d482-500, October 1, 1997]

	[Frontiers in Bioscience 2, d482-500, October 1, 1997] Reprints PubMed CAVEAT LECTOR
	PROSTAGLANDINS AND CANCER Susan M. Fischer The University of Texas M. D. Anderson Cancer Center, Science Park-Research Division, Smithville, TX 78957 Received 9/3/97 Accepted 9/23/97 2. INTRODUCTION The concept that PGs or other eicosanoids derived from fatty acids may play a role in the development of cancer is not a new one. A review written over twenty years ago (1) focused on three areas of involvement: i) humoral PGs as mediators of the symptoms of medullary carcinoma of the thyroid; ii) the role of PGs in hypercalcemia and bone resorption associated with neoplasia; and iii) the effects of inhibitors of PG synthesis, particularly indomethacin, on tumor growth. Subsequent work, reviewed by Karmali (2), was concerned with demonstrating an elevation of PGs in human and experimental tumors and showing that this affected tumor growth. Since this time, the literature has blossomed with reports on the effect of PGs on carcinogen metabolism, tumor cell proliferation, metastatic potential and the efficacy of inhibitors of PG synthesis in preventing tumor development (3, 4, 5). Not all of the reports are in agreement, however, leading to the conclusion that we do not yet know the exact role of PGs in cancer development and progression. Overall, however, several general observations can be made: i) there appears to be a direct relationship between the level of PGs synthesized, in humans or experimental animal models, and cancer incidence; and ii) for several experimental models and in some types of human cancer, particularly colon, inhibitors of PG synthesis are protective against cancer development. Although these latter observations have suggested that PGs (or other eicosanoids) can promote the development of tumors, there is also evidence that the inhibitors of PG synthesis commonly employed have anti-tumor functions independent of PG synthesis (4). This review focuses on how PG synthesis is regulated in animal and human studies and on the role of PGs in the major types of cancer, including skin, colon and breast. The several possible mechanisms by which high levels of PG synthesis may contribute to tumor development are also discussed. The ultimate goal of understanding the function and contribution of PGs to cancer is the use of this knowledge in designing better cancer prevention or intervention strategies.

[Frontiers in Bioscience 2, d482-500, October 1, 1997]
Reprints
PubMed
CAVEAT LECTOR

PROSTAGLANDINS AND CANCER

Susan M. Fischer

The University of Texas M. D. Anderson Cancer Center, Science Park-Research Division, Smithville, TX 78957

Received 9/3/97 Accepted 9/23/97

2. INTRODUCTION

The concept that PGs or other eicosanoids derived from fatty acids may play a role in the development of cancer is not a new one. A review written over twenty years ago (1) focused on three areas of involvement: i) humoral PGs as mediators of the symptoms of medullary carcinoma of the thyroid; ii) the role of PGs in hypercalcemia and bone resorption associated with neoplasia; and iii) the effects of inhibitors of PG synthesis, particularly indomethacin, on tumor growth. Subsequent work, reviewed by Karmali (2), was concerned with demonstrating an elevation of PGs in human and experimental tumors and showing that this affected tumor growth. Since this time, the literature has blossomed with reports on the effect of PGs on carcinogen metabolism, tumor cell proliferation, metastatic potential and the efficacy of inhibitors of PG synthesis in preventing tumor development (3, 4, 5). Not all of the reports are in agreement, however, leading to the conclusion that we do not yet know the exact role of PGs in cancer development and progression. Overall, however, several general observations can be made: i) there appears to be a direct relationship between the level of PGs synthesized, in humans or experimental animal models, and cancer incidence; and ii) for several experimental models and in some types of human cancer, particularly colon, inhibitors of PG synthesis are protective against cancer development. Although these latter observations have suggested that PGs (or other eicosanoids) can promote the development of tumors, there is also evidence that the inhibitors of PG synthesis commonly employed have anti-tumor functions independent of PG synthesis (4).

This review focuses on how PG synthesis is regulated in animal and human studies and on the role of PGs in the major types of cancer, including skin, colon and breast. The several possible mechanisms by which high levels of PG synthesis may contribute to tumor development are also discussed. The ultimate goal of understanding the function and contribution of PGs to cancer is the use of this knowledge in designing better cancer prevention or intervention strategies.