Use of isogenic human cancer cells for high-throughput screening and drug discovery View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2001-10

AUTHORS

Christopher J. Torrance, Vijai Agrawal, Bert Vogelstein, Kenneth W. Kinzler

ABSTRACT

Cell-based screening for novel tumor-specific drugs has been compromised by the lack of appropriate control cells. We describe a strategy for drug screening based on isogenic human cancer cell lines in which key tumorigenic genes have been deleted by targeted homologous recombination. As a test case, a yellow fluorescent protein (YFP) expression vector was introduced into the colon cancer cell line DLD-1, and a blue fluorescent protein (BFP) expression vector was introduced into an isogenic derivative in which the mutant K-Ras allele had been deleted. Co-culture of both cell lines allowed facile screening for compounds with selective toxicity toward the mutant Ras genotype. Among 30,000 compounds screened, a novel cytidine nucleoside analog was identified that displayed selective activity in vitro and inhibited tumor xenografts containing mutant Ras. The present data demonstrate a broadly applicable approach for mining therapeutic agents targeted to the specific genetic alterations responsible for cancer development. More... »

PAGES

940-945

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nbt1001-940

DOI

http://dx.doi.org/10.1038/nbt1001-940

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1019670801

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/11581659


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