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Research Articles

Anticancer medicines in development: assessment of bioactivity profiles within the National Cancer Institute anticancer screening data

¹ National Cancer Institute-Frederick, Developmental Therapeutics Program, Screening Technologies Branch, Laboratory of Computational Technologies and ² Laboratory of Computational Technologies, Science Applications International Corporation-Frederick, Inc., National Cancer Institute-Frederick, Frederick, Maryland

Requests for reprints: David G. Covell, National Cancer Institute-Frederick, Developmental Therapeutics Program, Screening Technologies Branch, Laboratory of Computational Technologies, Frederick, MD 21702. Phone: 301-846-5785; Fax: 301-846-6978. E-mail: covell{at}ncifcrf.gov

Abstract

We present an analysis of current anticancer compounds that are in phase I, II, or III clinical trials and their structural analogues that have been screened in the National Cancer Institute (NCI) anticancer screening program. Bioactivity profiles, measured across the NCI 60 cell lines, were examined for a correspondence between the type of cancer proposed for clinical testing and selective sensitivity to appropriately matched tumor subpanels in the NCI screen. These results find strongest support for using the NCI anticancer screen to select analogue compounds with selective sensitivity to the leukemia, colon, central nervous system, melanoma, and ovarian panels, but not for renal, prostate, and breast panels. These results are extended to applications of two-dimensional structural features to further refine compound selections based on tumor panel sensitivity obtained from tumor screening results. [Mol Cancer Ther 2007;6(8):2261–70]

Grant support: Federal funds from the National Cancer Institute, NIH, under contract no. NO1-CO-12400, and the Developmental Therapeutics Program of the National Cancer Institute Division of Cancer Treatment and Diagnosis.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

³ http://www.phrma.org

⁴ Supplementary data for this article are available at Molecular Cancer Therapeutics Online (http://mct.aacrjournals.org/). Supplementary Figs. S1 and S2 provide histograms for the number of AMIDs in each cancer class and the number count of AMIDs in each cancer class, respectively.

⁵ http://www.phrma.org/medicines_in_developments

⁶ http://integrity.prous.com

Received 3/20/07; revised 5/25/07; accepted 6/18/07.