In vitro assays for anticancer drug discovery--a novel approach based on engineered mammalian cell lines.

Despite decisive progress in understanding the molecular biology of cancer development, cytotoxic anticancer drugs continue to be the cornerstone of modern antitumor therapies. The developmental therapeutics program, initiated by the US National Institutes of Health's National Cancer Institute in the early 1990s, pioneered massive-scale screening for agents able to phenotypically interfere with the growth and viability of neoplastic cell lines derived from a representative panel of human carcinogenic tissues. Capitalizing on advanced knowledge of molecular processes particular for neoplastic cell characteristics, target-specific screening scenarios became since increasingly popular. With drug targets defined, natural and synthetic (combinatorial) compound/peptide/nucleic acid libraries available and the high-throughput screening technology of the systems' biology era in place, the quo vadis of anticancer drug discovery seems to be well determined. We review recent advances in cytotoxic anticancer drug assay design with emphasis on a novel mammalian cell-based anticancer drug finder technology for the discovery of cytotoxic drugs with fewer side-effects on non-dividing cells.