An Information-Intensive Approach to the Molecular Pharmacology of Cancer-Reference-Cited by-同舟云学术

An Information-Intensive Approach to the Molecular Pharmacology of Cancer

Published:1997-01-17 Issue:5298 Volume:275 Page:343-349
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Weinstein John N.¹,Myers Timothy G.¹,O'Connor Patrick M.¹,Friend Stephen H.²,Fornace Albert J.¹,Kohn Kurt W.¹,Fojo Tito³,Bates Susan E.³,Rubinstein Lawrence V.⁴,Anderson N. Leigh⁵,Buolamwini John K.¹,van Osdol William W.¹,Monks Anne P.⁶,Scudiero Dominic A.⁶,Sausville Edward A.⁷,Zaharevitz Daniel W.⁸,Bunow Barry¹,Viswanadhan Vellarkad N.¹,Johnson George S.⁹,Wittes Robert E.¹⁰,Paull Kenneth D.⁸

Affiliation:

1. J. N. Weinstein, T. G. Myers, P. M. O'Connor, A. J. Fornace Jr., K. W. Kohn, J. K. Buolamwini, W. W. van Osdol, and V. N. Viswanadhan are at the Laboratory of Molecular Pharmacology (LMP), Division of Basic Science, National Cancer Institute (NCI), National Institutes of Health (NIH), Building 37, Room 5C-25, 9000 Rockville Pike, Bethesda, MD 20892, USA.

2. S. H. Friend is at the Fred Hutchinson Cancer Research Center-NCI, Seattle, WA 98105, USA.

3. T. Fojo and S. E. Bates are in the Medicine Branch, Division of Clinical Science, NCI, NIH, Bethesda, MD 20892, USA.

4. L. V. Rubinstein is in the Biometric Research Branch, Cancer Therapy Evaluation Program, Division of Cancer Treatment, Diagnosis, and Centers (DCTDC), NCI, NIH, Bethesda, MD 20892, USA.

5. N. L. Anderson is with Large Scale Biology, Rockville, MD 20850, USA.

6. A. P. Monks and D. A. Scudiero are at the SAIC-NCI-Frederick Cancer Research and Development Center (FCRDC), Frederick, MD 21701, USA.

7. E. A. Sausville is in the Developmental Therapeutics Program (DTP), DCTDC, NCI, NIH, Bethesda, MD 20892, USA.

8. D. W. Zaharevitz and K. D. Paull are in the Information Technology Branch, DTP, DCTDC, NCI, NIH, Bethesda, MD 20892, USA.

9. G. S. Johnson is in the Grants and Contracts Operations Branch, DTP, DCTDC, NCI, NIH, Bethesda, MD 20892, USA.

10. R. E. Wittes is in the Office of the Director, DCTDC, NCI, NIH, Bethesda, MD 20892, USA.

Abstract

Since 1990, the National Cancer Institute (NCI) has screened more than 60,000 compounds against a panel of 60 human cancer cell lines. The 50-percent growth-inhibitory concentration (GI 50 ) for any single cell line is simply an index of cytotoxicity or cytostasis, but the patterns of 60 such GI 50 values encode unexpectedly rich, detailed information on mechanisms of drug action and drug resistance. Each compound's pattern is like a fingerprint, essentially unique among the many billions of distinguishable possibilities. These activity patterns are being used in conjunction with molecular structural features of the tested agents to explore the NCI's database of more than 460,000 compounds, and they are providing insight into potential target molecules and modulators of activity in the 60 cell lines. For example, the information is being used to search for candidate anticancer drugs that are not dependent on intact p53 suppressor gene function for their activity. It remains to be seen how effective this information-intensive strategy will be at generating new clinically active agents.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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