A strategy for screening anti-tumor drugs utilizing oncogenes encoded in retroviral vectors.

摘要: A novel strategy for isolating potential anti-tumor drugs is presented. It predicated on the idea that future will be specific inhibitors of signal-transduction pathways responsible cell proliferation. Briefly, retroviral vectors are used to introduce focus-forming oncogenes into a test population target cells, which grown confluence and treated with inhibitors. The screened ability suppress development transformed foci without killing confluent monolayer non-transformed quiescent cells. For this work, panel was first against oncogene ras. protein kinase C (PKC) inhibitor CGP 41251 tyrosine (PTK) 45047 suppressed ras-induced focus formation left viable Focus inhibition reversible; conversely, drug addition developing retarded further expansion. generally blocked proliferation ras or control suggesting cannot substitute PKC. PTK erbstatin 520 phosphatase okadaic acid failed inhibit at concentrations toxic monolayer. Lavendustin 47778A showed neither nor toxicity. In complementary screen, single (CGP 41251) tested several oncogenes, including src, raf polyomavirus middle T antigen. by all suppressed. has advantages over current drug-screening assays, it can adapted large-scale screening many oncogenes. © 1996 Wiley-Liss, Inc.