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A multivariate insight into the in vitro antitumour screen database of the National Cancer Institute: classification of compounds, similarities among cell lines and the influence of molecular targets

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Abstract

A multivariate insight into the in vitro antitumour screen database of the NCI by means of the SIMCA package allows to propose hypotheses on the mechanism of action of novel anticancer compounds. As an example, the application of multivariate analysis to the NCI standard database provided clues to the classification of drugs whose mechanism is either unknown or controversial. Moreover, the influence of intrinsic biochemical cell line properties (molecular targets) on the sensitivity to drug treatment could be evaluated simultaneously for classes of compounds which act by the same mechanism. Interestingly, the present approach can also provide a correlation between the molecular targets and the therapeutical fingerprint of novel active compounds thus suggesting specific biochemical studies for the investigation of new mechanisms of drug action and resistance. The statistical approach reported here represents a valuable tool for handling the enormous data sets deriving from recent genome-wide investigations of gene expression in the NCI cell lines.

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References

  1. Database resources currently available on the World Wide Web: http://www.dtp.nci.nih.gov/.

  2. Weinstein, J. N., et al. Science, 258 (1992) 447.

    Google Scholar 

  3. Weinstein, J. N., Myers, T., Buolamwini, J., Raghavan, K., van Osdol, W., Licht, J., Viswanadhan, V. N., Kohn, K. W., Rubinstein, L. V., Koutsoukos, A. D. et al., Stem Cells, 12 (1994) 13; b. Chabner, B. A., Weinstein, J. N., Paull, K. D., Grever, M. R., (Eds.: Banzet, P., Holland, J. F., Khayat, D., Weil, M.), in Cancer Treatment, an Update, Springer-Verlag, Paris, 1994, pp. 10-16; c. Koutsoukos, A. D., Rubinstein, L. V., Faraggi, D., Simon, R. M., Kalyandrug, S., Weinstein, J. N., Kohn, K. W., Paull, K. D., Stat. Med., 13 (1994) 719; d. Bates, S. E. et al., J. Cancer Res. Clin. Oncol., 121 (1995) 495.

    Google Scholar 

  4. Wold, S., & Sjöström, M., American Chemical Society Symposium Series 52, 1977, pp. 243-282.

  5. SIMCA 7.0 Manual Umetri AB, Umeå, Sweden.

  6. Wold, S., Chemometr. Intell. Lab. Syst., 2 (1987) 37.

    Google Scholar 

  7. Wold, S., Technometrics, 20 (1978) 397.

  8. Mardia, K. V., Kent, J. T., Biddy, J. M., in Multivariate Analysis, Academic Press, London, 1979.

    Google Scholar 

  9. Wold, S., Albano, C., Dunn, W. J., Esbensen, K., Hellberg, S., Johannsson, E., Sjöström, M. (Eds.: Martens, H. and Russwurm, H.), in Food Research and Data Analysis, Applied Science, London, 1983, pp. 147-162.

    Google Scholar 

  10. Wold, S., Albano, C., Dunn, W. J., Edlund, U., Esbensen, K., Geladi, P., Hellberg, S., Lindenberg, W., Sjöström, M. (Ed. B. R. Kowalski NATO ASI Series C.), Chemical Mathematics and Statistics in Chemistry, D. Reidel, Dordrecht, 1984, pp. 17-95.

    Google Scholar 

  11. Clementi, S., Cruciani, G., Curti, G., Anal. Chimica Acta, 191 (1986) 149.

    Google Scholar 

  12. WWW under http://www.unict.it/dipchi/.

  13. Koutsoukos, A. D., Rubinstein, L. V., Faraggi, D., Simon, R. M., Kalyandrug, S., Weinstein, J. N., Kohn, K. W., Paull, K. D., Stat. Med., 13 (1994) 719.

    Google Scholar 

  14. Chen, H., Patel D. J., J. Mol. Biol., 246 (1995) 164.

    Google Scholar 

  15. Ren, J., Chaires, J. B., Biochemistry, 38 (1999) 16067.

    Google Scholar 

  16. Pommier, Y., Fesen, M. R., Goldwasser, F., (Eds. B. A. Chabner and D. L. Longo), Cancer Chemoterapy: Principles and Practice 2nd ed., J. B. Lippincott Co., Philadelphia, 1995.

    Google Scholar 

  17. Malone, H., Atassi, G., Anticancer Drugs, 8 (1997) 811.

    Google Scholar 

  18. Jayaran, H. N., Lui, M. S., Plowman, J., Pillwein, K., Reardon, M. A., Elliot, W. L., Weber, G., Cancer Chemother. Pharmacol., 26 (1990) 88.

    Google Scholar 

  19. Ross, D. T., Scherf, U., Eisen, M. B., Perou, C. M., Rees, C., Spellman, P., Iyer, V., Jeffrey, S. S., Van De Rijn, M., Waltham, M., Pergamenschikov, A., Lee, J. C., Lashkari, D., Shalon, D., Myers, T. G., Weinstein, J. N., Botstein, D., Brown, P. O., Nat Genet. 24 (2000) 227.

    Google Scholar 

  20. Scherf, U., Ross, D., Waltham, M., Smith, L., Lee, J., Tanabe, L., Kohn, K., Reinhold, W., Myers, T., Andrews, D., Scudiero, D., Eisen, M., Sausville, E., Pommier, Y., Botstein, D., Brown, P., Weinstein, J., Nat Genet., 24 (2000) 236.

    Google Scholar 

  21. Peters, A. C., Smythe, A. M., Wu, L., Monks, A., Boyd, M. R. and Shoemaker, R. H., Oncology Reports, 1 (1994) 907.

    Google Scholar 

  22. O'Connor, P. M., Jackman, J., Bae, I., Myers, T. G., Fan, S., Mutoh, M., Scudiero, D. A., Monks, A., Sausville, E. A., Weinstein, J. N., Friend, S., Fornace, A. J. J., Kohn, K. W., CancerRes., 57 (1997) 4285.

    Google Scholar 

  23. Weinstein, J. N., Myers, T. G., O'Connor, P. M., Friend, S. H., Fornace, A. J. J., Kohn, K. W., Foyo, T., Bates, S. E., Rubinstein, L. V., Anderson, N. L., Buolamwini, J. K., Van Osdol, W. W., Monks, A. P., Scudiero, D. A., Sausville, E. A., Zaharevitz, D. W., Bunow, B., Viswanadhan, V. N., Johnson, G. S., Wittes, R. E., Paull, K. D., Science, 275 (1997) 343.

    Google Scholar 

  24. Shi, L. M., Myers, T. G., Fan, Y., O'Connor, P. M., Paull, K. D., Friend, S. H., Weinstein, J. N., Mol. Pharmacol., 53 (1998) 241.

    Google Scholar 

  25. Shi, L. M., Fan, Y., Myers, T. G., O' Connor, P. M., Paull, K. D., Friend, S. H., Weinstein, J. N., J. Chem. Inf. Comput. Sci., 38 (1998) 189.

    Google Scholar 

  26. Hollstein, M., Sidransky, D., Vogelstein, B., Harris, C. C., Science, 253 (1991) 49.

    Google Scholar 

  27. Hollstein, M., Herenhahn, M., Yang, Q., Bartsch, H., Wang, Z. Q., Hainaut, P., Mutat. Res., 431 (1999) 199.

    Google Scholar 

  28. Harris, C. C., J. Natl. Cancer Inst., 88 (1996) 1442.

    Google Scholar 

  29. Lee, J.S., Paull, K., Alvarez, M., Hose, C., Monks, A., Grever, M., Fojo, A. T. and Bates, S., Mol. Pharm., 46 (1994) 628.

    Google Scholar 

  30. Flens, M. J., Scheffer, G. L., Van der Valk, P., Broxterman, H. J., Eijdems, E. W., Huysmans, A. C., Izquierdo, M. A., Scheper, R. J., Int. J. Cancer, 73 (1997) 249.

    Google Scholar 

  31. Alvarez, M., Robey, R., Sandor, V., Nishiyama, K., Matsumoto, Y., Paull, K., Bates, S., Fojo, T., Mol. Pharmacol., 54 (1998) 802.

    Google Scholar 

  32. Izquierdo, M. A., Shoemaker, R. H., Flens, M. J., Scheffer, G. L., Wu, L., Prather, T. R., Scheper, R. J., Int J. Cancer, 65 (1996) 230.

    Google Scholar 

  33. Berggren, M., Gallegos, A., Gasdaska, J. R., Gasdaska, P. Y., Warneke, J. and Powis, G., Anticancer Res., 16 (1996) 3459.

    Google Scholar 

  34. Lazo, J. S., Kuo, S. M., Woo, E. S., Pitt, B. R., Chem. Biol. Interact., 111-112 (1998) 255.

    Google Scholar 

  35. Woo, E. S., Monks, A., Watkins, S. C., Wang, A. S., Lazo, J. S., Cancer Chem. Pharmacol., 41 (1997) 61.

    Google Scholar 

  36. Kasahara, K., Fujiwara, Y., Nishio, K., Ohmori, T., Sugimoto, Y., Komiya, K., Matsuda, T., Saijo, N., Cancer. Res., 51 (1991) 3237.

    Google Scholar 

  37. Wold, S., Sjöström, M., Chemometr. Intell. Lab. Syst., 44 (1998) 3.

    Google Scholar 

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Authors and Affiliations

  1. Dipartimento di Scienze Chimiche, Università di Catania, Viale A. Doria 6, 95125, Catania, Italy

    Giuseppe Musumarra, Daniele F. Condorelli, Alessandro S. Costa & Maria Fichera

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  1. Giuseppe Musumarra
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  2. Daniele F. Condorelli
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  3. Alessandro S. Costa
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  4. Maria Fichera
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Musumarra, G., Condorelli, D.F., Costa, A.S. et al. A multivariate insight into the in vitro antitumour screen database of the National Cancer Institute: classification of compounds, similarities among cell lines and the influence of molecular targets. J Comput Aided Mol Des 15, 219–234 (2001). https://doi.org/10.1023/A:1008171426412

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