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Enhancement of tumor growth by drugs with some common molecular actions
Author(s) -
LaBella Frank S.,
Brandes Lorne J.
Publication year - 1996
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/(sici)1098-2744(199606)16:2<68::aid-mc2>3.0.co;2-j
Subject(s) - biology , antiestrogen , tamoxifen , ovarian cancer , cancer , pharmacology , pharmacophore , drug , cancer research , bioinformatics , breast cancer , genetics
A group of structurally related drugs representing diverse therapeutic classes share, among a number of pharmacological properties, enhancement 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 antiestrogen tamoxifen has been shown in controlled clinical studies to increase the incidence of uterine and gastrointestinal cancer and to accelerate the course of gastric cancer, and the tamoxifen analogue clomiphene has been linked to neuroblastoma and the tricyclic group of antidepressants to ovarian cancer. The determination of drug affinities for protein modulators of cell growth, proliferation, and transformation suggests a strategy for identifying at least some classes of chemicals that impart oncologic risks to humans. © 1996 Wiley‐Liss, Inc.