ENHANCEMENT OF TUMOR-GROWTH BY DRUGS WITH SOME COMMON MOLECULAR ACTIONS

A group of structurally related drugs representing diverse therapeutic classes share, among a number of pharmacological properties, enhancem ent of tumor growth in several rodent models of malignancy. One common action, the inhibition of histamine binding to and catalytic activity of cytochrome P450 monooxygenases, is highly correlated with potency to enhance tumor growth. Among members of this drug ensemble, the anti estrogen tamoxifen has been shown in controlled clinical studies to in crease the incidence of uterine and gastrointestinal cancer and to acc elerate the course of gastric cancer, and the tamoxifen analogue clomi phene has been linked to neuroblastoma and the tricyclic group of anti depressants to ovarian cancer. The determination of drug affinities fo r protein modulators of cell growth, proliferation, and transformation suggests a strategy for identifying at least some classes of chemical s that impart oncologic risks to humans. (C) 1996 Wiley-Liss, Inc.