The development of alkylphosphocholines as signal transduction inhibitors: experimental and clinical challenges.

Alkylphosphocholines are a new class of anticancer agents. Their mode of action is considered to be related to the inhibition of phospholipase C and protein kinase C. These enzymes play a major role in intracellular signalling pathways. Their inhibition by alkylphosphocholines leads in the dimethylbenzanthracene-induced mammary carcinoma of the rat to a response pattern similar to that of the antiestrogen zindoxifene. This suggests that the inhibition of transcription factor formation might be the common pathway for alkylphosphocholines and antihormones. Based on the experimental dose-response pattern, new clinical strategies for dose finding and response evaluation will have to be developed for inhibitors of signal transduction, such as alkylphosphocholines.