Matrix Metalloproteinase Inhibitors and Cancer—Trials and Tribulations

American Association for the Advancement of Science (AAAS) - Tập 295 Số 5564 - Trang 2387-2392 - 2002
Lisa M. Coussens1, Barbara Fingleton2, Lynn M. Matrisian2
1Department of Pathology and Cancer Research Institute, University of California, 2340 Sutter Street, San Francisco, CA 94143, USA.
2Department of Cancer Biology, Vanderbilt University, Nashville, TN 37232, USA

Tóm tắt

For at least 30 years, matrix metalloproteinases (MMPs) have been heralded as promising targets for cancer therapy on the basis of their massive up-regulation in malignant tissues and their unique ability to degrade all components of the extracellular matrix. Preclinical studies testing the efficacy of MMP suppression in tumor models were so compelling that synthetic metalloproteinase inhibitors (MPIs) were rapidly developed and routed into human clinical trials. The results of these trials have been disappointing. Here we review the studies that brought MPIs into clinical testing and discuss the design and outcome of the trials in light of new information about the cellular source, substrates, and mode of action of MMPs at different stages of tumor progression. The important lessons learned from the MPI experience may be of great value for future studies of MPIs and for cancer drug development in general.

Từ khóa


Tài liệu tham khảo

J. F. Woessner H. Nagase Matrix Metalloproteinases and TIMPs (Oxford Univ. Press New York ed. 1 2000).

McCawley L. J., Matrisian L. M., Curr. Opin. Cell Biol. 13, 534 (2001).

___, Mol. Med. Today 6, 149 (2000).

Stetler-Stevenson W. G., Am. J. Pathol. 148, 1345 (1996).

DeClerck Y. A., Imren S., Eur. J. Cancer 30A, 2170 (1994).

Montgomery A. M. P., Mueller B. M., Reisfeld R. A., Taylor S. M., DeClerck Y. A., Cancer Res. 54, 5467 (1994).

Khokha R., J. Natl. Cancer Inst. 86, 299 (1994).

Koop S., et al., Cancer Res. 54, 4791 (1994).

Schultz R. M., Silberman S., Persky B., Bajkowski A. S., Carmichael D. F., Cancer Res. 48, 5539 (1988).

Alvarez O. A., Carmichael D. F., DeClerck Y. A., J. Natl. Cancer Inst. 82, 589 (1990).

Khokha R., et al., Science 244, 947 (1989).

Buck T. B., Yoshiji H., Harris S. R., Bunce O. R., Thorgeirsson U. P., Ann. N.Y. Acad. Sci. 878, 732 (1999).

Martin D. C., Ruther U., Sanchez-Sweatman O. H., Orr F. W., Khokha R., Oncogene 13, 569 (1996).

Whittaker M., Floyd C. D., Brown P., Gearing A. J. H., Chem. Rev. 99, 2735 (1999).

Reich R., et al., Cancer Res. 48, 3307 (1988).

Sternlicht M. D., Bergers G., Emerg. Ther. Targets 4, 609 (2000).

Brown P. D., Expert. Opin. Investig. Drugs 9, 2167 (2000).

Sledge G. W., Qulali M., Goulet R., Bone E. A., Fife R., J. Natl. Cancer Inst. 87, 1546 (1995).

Nelson A. R., Fingleton B., Rothenberg M. L., Matrisian L. M., J. Clin. Oncol. 18, 1135 (2000).

J. D'Armiento et al. Mol. Cell. Biol. 15 5732 (1995).

Rudolph-Owen L. A., Chan R., Muller W. J., Matrisian L. M., Cancer Res. 58, 5500 (1998).

10.1016/S0092-8674(00)81009-0

Wilson C. L., Heppner K. J., Labosky P. A., Hogan B. L. M., Matrisian L. M., Proc. Natl. Acad. Sci. U.S.A. 94, 1402 (1997).

Masson R., et al., J. Cell Biol. 140, 1535 (1998).

Bergers G., et al., Nature Cell Biol. 2, 737 (2000).

10.1016/S0092-8674(00)00139-2

Heppner Goss K. J., Brown P. D., Matrisian L. M., Int. J. Cancer 78, 629 (1998).

Bergers G., Javaherian K., Lo K. M., Folkman J., Hanahan D., Science 284, 808 (1999).

Stetler-Stevenson W. G., J. Clin. Invest. 103, 1237 (1999).

Bird J., Montana J. G., Wills R. E., Baxter A. D., Owens D. A., Chem. Abstr. 129, 22571 (1998).

Nemunaitis J., et al., Clin. Cancer Res. 4, 1101 (1998).

Primrose J. N., et al., Br. J. Cancer 79, 509 (1999).

Rosemurgy A., et al., Am. J. Clin. Oncol. 22, 247 (1999).

M. Gore R. A'Hern

Stankiewicz M., Slevin M., Lancet 348, 263 (1996).

Bramhall S. R., Rosemurgy A., Brown P. D., Bowry C., Buckels J. A., J. Clin. Oncol. 19, 3447 (2001).

British Biotech PLC www.britbio.com/news/173 183analysis.pdf (2001).

Fielding J., et al., Proc. Am. Soc. Clin. Oncol. 19, 240A (2000).

Bayer Corporation www.bayerusa.com/news/co0221.asp (1999).

Moore M., et al., Proc. Am. Soc. Clin. Oncol. 19, 240a (2001).

Kruger A., et al., Cancer Res. 61, 1272 (2001).

Pozzi A., et al., Proc. Natl. Acad. Sci. U.S.A. 97, 2202 (2000).

Pozzi A., LeVine W. F., Gardner H. A., Oncogene 21, 272 (2002).

(2001).

Agouron Pharmaceuticals Inc. www.agouron.com/Pages/press_releases/pr080400.html (2000).

(2001).

(2001).

Wynn R. L., Gen. Dent. 47, 19 (1999).

Michael M., et al., J. Clin. Oncol. 17, 1802 (1999).

Hidalgo M., Eckhardt S. G., J. Natl. Cancer Inst. 93, 178 (2001).

Cianfrocca M., et al., J. Clin. Oncol. 20, 153 (2002).

Bremer C., Tung C. H., Weissleder R., Nature Med. 7, 743 (2001).

Glasspool R. M., Evans T. R., Eur. J. Cancer 36, 1661 (2000).

Louie A. Y., et al., Nature Biotechnol. 18, 321 (2000).

Druker B. J., Lydon N. B., J. Clin. Invest. 105, 3 (2000).

10.1056/NEJM200104053441401

British Biotech PLC www.britbio.com/news/131.pdf (2000).

British Biotech PLC www.britbio.com/news/140_result.pdf (2001).

British Biotech PLC www.britbio.com/news/186.pdf (2000).

We thank P. Brown A. Sandler M. Rothenberg D. Shalinsky Z. Werb G. Bergers and the referees for advice and for critically reviewing the manuscript. We also acknowledge our colleagues who provided valuable information on MMP function but were not mentioned because of space constraints. Supported by UCSF Comprehensive Cancer Center grant NCI CA72006 the V Foundation for Cancer Research and the Edward Mallinckrodt Foundation (L.M.C.) and by NCI grants R01CA60867 R01CA84360 P30CA68485 and P50CA90949 and the Vanderbilt-Ingram Cancer Center (B.F. and L.M.M.). L.M.M. receives research support from Pfizer Global Inc. and Abbott Laboratories and has served as a consultant for Bristol-Myers Squibb Roche Biosciences and Abbott Laboratories. B.F. has served as a consultant for Roche International and for Pfizer Global Inc.

Thông tin
Thông tin xuất bản

American Association for the Advancement of Science (AAAS)

Tập 295 Số 5564

2387-2392

Thông tin tác giả