Ether lipids in cancer chemotherapy.

Abstract

There is considerable evidence that certain ether lipids such as 1-0-octadecyl-2-0-methyl-rac-glycero-3-phosphocholine represent a new class of antineoplastic agents. These ether lipids have been shown to be cytotoxic for a wide variety of tumors. The site of action of ether lipids appears to be the cell membrane, where they inhibit the biosynthesis of phosphatidylcholine as well as the activity of protein kinase C. However, it remains uncertain that these effects represent the only mechanism for the cytotoxic action of these ether lipids. Further experiments to elucidate the molecular mechanisms of the cytotoxic action of these compounds are necessary. Clinical phase I pilot trials have been completed showing encouraging tumor response in a small number of patients treated. Some of these ether lipids are selectively cytotoxic to leukemic cells sparing of normal cells within a certain dose range. Thus, they are uniquely suitable for purging residual leukemic cells from remission marrow used for autologous bone marrow transplantation. A phase I/II study of autologous bone marrow transplantation in acute leukemia using bone marrow cells treated with ether lipids is in progress.