DTP’s anticancer screening program generates vast quantities of data that are captured in a computerized database. The development of COMPARE algorithm has greatly enhanced the value of the human tumor cell line assay as a discovery tool.
The current in vitro anticancer screen, which is used to evaluate the efficacy of synthetic compounds and natural products, was developed over several years and initiated in April 1990. The current version employs 59 human tumor cell lines that have been grouped in disease subpanels. At maximum capacity, the screen evaluated approximately 1,000 compounds and natural product extracts each month. The decision that there would be no alteration of the assay method and cell lines employed in the screen for an extended period of time permitted the evaluation of thousands of compounds under identical conditions.
To date, DTP has evaluated more than 88,000 pure compounds and more than 34,000 crude extracts against the panel of human tumor cell lines. The resultant data are analyzed using a program called COMPARE. A probe or “seed” compound can be specified by using the compound’s NCI accession number (the NSC number). The COMPARE algorithm then proceeds to rank the entire database of tested compounds in the order of the similarity of the responses, shown as mean cell graph “fingerprints” or patterns, of the cell lines to the compounds in the database to the responses of the cell lines to the seed compound. Similarity of pattern to that of the seed is expressed quantitatively as a Pearson correlation coefficient. The results obtained with the COMPARE algorithm indicate that compounds high in this ranking may possess a mechanism of action similar to that of the seed compound.
In 1985, the hypothesis was put forward that the screen could discover cell-type specific agents with clinical activity against solid tumors. The emerging reality is that correlation of in vitro histology to clinical activity is poor, but the pattern of cellular sensitivity and resistance of the cell lines to the drug correlates with molecular target expression.
For public access to all public data
Use the PUBLIC COMPARE web site.
For suppliers and DTP personnel
Use the PRIVATE COMPARE web site.
Bates SE. Molecular targets in the National Cancer Institute drug screen. J Cancer Res Clin Oncol 1995;121:495-500.
Sausville EA, Johnson JI. Molecules for the millennium: how will they look? New drug discovery year 2000. Br J Cancer 2000;83:1401-1404.
Monks A, Scudiero DA, Johnson GS, Paull KD, Sausville EA. The NCI anti-cancer drug screen: a smart screen to identify effectors of novel targets. Anti-Cancer Drug Des 1997;12:533-541.