A phase I trial of the farnesyl transferase inhibitor SCH66336: Evidence for biological and clinical activity

Cancer Research

Volumn 60, Issue 7, 2000, Pages 1871-1877

  Adjei, Alex A ^a   Erlichman, Charles ^a   Davis, Jenny N ^a   Cutler, David L ^b   Sloan, Jeff A ^a   Marks, Randolph S ^a   Hanson, Lorelei J ^a   Svingen, Phyllis A ^a   Atherton, Pamela ^a   Bishop, W Robert ^b   Kirschmeier, Paul ^b   Kaufmann, Scott H ^a  

^a MAYO CLINIC   (United States)

^b MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

LAMIN A; LONAFARNIB; PROTEIN FARNESYLTRANSFERASE INHIBITOR;

ADULT; AGED; ANTINEOPLASTIC ACTIVITY; ARTICLE; CHEEK MUCOSA; CLINICAL ARTICLE; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DIARRHEA; DRUG EFFICACY; ENZYME INHIBITION; FATIGUE; FEMALE; GALLBLADDER CANCER; HUMAN; HUMAN CELL; IMMUNOHISTOCHEMISTRY; KIDNEY CANCER; KIDNEY FAILURE; LEUKOPENIA; LUNG NON SMALL CELL CANCER; MALE; MAXIMUM PERMISSIBLE DOSE; NAUSEA; NEUTROPENIA; PANCREAS CANCER; PHASE 1 CLINICAL TRIAL; PRIORITY JOURNAL; PROSTATE CANCER; SARCOMA; SOLID TUMOR; THROMBOCYTOPENIA; VOMITING;

ADULT; AGED; AGED, 80 AND OVER; ALKYL AND ARYL TRANSFERASES; ANTINEOPLASTIC AGENTS; DOSE-RESPONSE RELATIONSHIP, DRUG; ENZYME INHIBITORS; FARNESYLTRANSTRANSFERASE; FEMALE; HUMANS; LAMINS; MALE; MIDDLE AGED; MOUTH MUCOSA; NEOPLASMS; NUCLEAR PROTEINS; PIPERIDINES; PROTEIN PRECURSORS; PYRIDINES;

EID: 0034071688     PISSN: 00085472     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (34)

1. Farnsworth, C. C., Wolda, S. L., Gelb, M. H., and Glomset, J. A. Human lamin B contains a farnesylated cysteine residue. J. Biol. Chem., 264: 20422-20429, 1989.
2. Sinensky, M., Fantle, K., Trujillo, M. A., McLain, T., Kupfer, A., and Dalton, M. The processing pathway of prelamin A. J. Cell Sci., 107: 61-67, 1994.
3. Inglese, J., Glickman, J. F., Lorenz, W., Caron, M. G., and Lefkowitz, R. J. Isoprenylation of a protein kinase. Requirement of farnesylation/α-carboxyl methylation for full enzymatic activity of rhodopsin kinase. J. Biol. Chem., 267: 1422-1425, 1992.
4. Lai, R. K., Perez-Sala, D., Canada, F. J., and Rando, R. R. The γ subunit of transducin is farnesylated. Proc. Natl. Acad. Sci. USA, 87: 7673-7677, 1990.
5. Lowy, D. R., and Williamson, B. M. Function and regulation of Ras. Annu. Rev. Biochem., 62: 851-891, 1993.
6. Downward, J. Ras signalling and apoptosis. Curr. Opin. Genet. Dev., 8: 9-54, 1998.
7. Bos, J. L. Ras oncogenes in human cancer: a review. Cancer Res., 49: 4682-4689, 1989.
8. Kato, K., Cox, A. D., Hisaka, M. M., Graham, S. M., Buss, J. E., and Der, C. J. Isoprenoid addition to Ras proteins is the critical modification for its membrane association and transforming activity. Proc. Natl. Acad. Sci., 89: 6403-6407, 1992.
9. Whyte, D. B., Kirschmeier, P., Hockenberry, T. N., Nunez-Oliva, I., James, L., Catino, J. J., Bishop, W. R., and Pai, J. K. K-and N-ras are geranylgeranylated in cells treated with farnesyl protein transferase inhibitors. J. Biol. Chem., 272: 14459-14464, 1997.
10. Sepp-Lorenzino, L., Ma, Z., Rands, E., Kohl, N. E., Gibbs, J. B., Oliff, A., and Rosen, N. A peptidomimetic inhibitor of farnesyl:protein transferase blocks the anchorage-dependent and -independent growth of human tumor cell lines. Cancer Res., 55: 5302-5309, 1995.
11. Cox, A. D., and Der, C. J. Farnesyltransferase inhibitors and cancer treatment: targeting simply Ras? Biochim. Biophys. Acta, 1333: F51-F71, 1997.
12. Lebowitz, P. F., and Prendergast, G. C. Non-Ras targets of farnesyltransferase inhibitors: focus on Rho. Oncogenc, 17: 1439-1445, 1998.
13. Bishop, W. R., Bond, R., Petrin, J., Wang, L., Patton, R., Doll, R., Njoroge, G., Catino, J., Schwartz, J., and Windsor, W. Novel tricyclic inhibitors of farnesyl transferase. J. Biol. Chem., 270: 30611-30618, 1995.
14. Liu, M., Bryant, M. S., Chen, J., Lee, S., Yaremko, B., Lipari, P., Malkowski, M., Ferrari, E., Nielsen, L., Prioli, N., Dell, J., Sinha, D., Syed, J., Korfmacher, W. A., Nomeir, A. A., Lin, C. C., Wang, L., laveras, A. G., Doll, R. J., Njoroge, F. G., Mallams, A. K., Remiszewski, S., Catino, J. J., Girijavallabhan, V. M., and Bishop, W. R. Antitumor activity of SCH66336, an orally bioavailable tricyclic inhibitor of farnesyl protein transferase, in human tumor xenograft models and wap-ras transgenic mice. Cancer Res., 58: 4947-4956, 1998.
15. Anonymous. Common Toxicity Criteria Version 2.0. Bethesda, MD: National Cancer Institute, 1998.
16. Loewinger, L., and McKeon, F. Mutations in the nuclear lamin proteins resulting in their aberrant assembly in the cytoplasm. EMBO J., 7: 2301-2309, 1988.
17. Sinensky, M., Fantle, K., and Dalton, M. An antibody which specifically recognizes prelamin A but not mature lamin A: application to detection of blocks in farnesylation-dependent protein processing. Cancer Res., 54: 3229-3232, 1994.
18. Kaufmann, S. H., Svingen, P. A., Gore, S. D., Armstrong, D. K., Cheng, Y-C., and Rowinsky, E. K. Altered formation of topotecan-stabilized topoisomerase I-DNA adducts in human leukemia cells. Blood. 89: 2098-2104, 1997.
19. Smith, P. K., Krohn, R. I., Hermanson, G. T., Mallia, A. K., Gartner, F. H., Provenzano, M. D., Fujimoto, E. K., Goeke, N. M., Olson, B. J., and Klenk, D. C. Measurement of protein using hicinchoninic acid. Anal. Biochem., 150: 76-85, 1985.
20. James, G. L., Goldstein, J. L., Pathak, R. K., Anderson, R. G., and Brown, M. S. PxF, a prenylated protein of peroxisomes. J. Biol. Chem., 269: 14182-14190, 1994.
21. Beck, L. A., Hosick, T. J., and Sinensky, M. Isoprenylation is required for the processing of the lamin A precursor. J. Cell Biol., 110: 1489-1499, 1990.
22. Lutz, R. J., Trujillo, M. A., Denham, K. S., Wenger, L., and Sinensky, M. Nucleoplasmic localization of prelamin A: implications for prenylation-dependent lamin A assembly into the nuclear lamina. Proc. Natl. Acad. Sci. USA, 89: 3000-3004, 1992.
23. Kilic, F., Dalton, M. B., Burrell, S. K., Mayer, J. P., Patterson, S. D., and Sinensky, M. In vino assay and characterization of the farnesylation-dependent prelamin A endoprotease. J. Biol. Chem., 272: 5298-5304, 1997.
24. Heasley, L. E., Thaler, S., Nicks, M., Price, B., Skorecki, K., and Nemenoff, R. A. Induction of cytosolic phospholipase A2 by oncogenic ras in human non-small cell lung cancer. J. Biol. Chem., 272: 14501-14504, 1997.
25. Kaufmann, S. H. Additional members of the rat liver lamin polypeptide family: structural and immunological characterization. J. Biol. Chem., 264: 13946-13955, 1989.
26. Gibbs, J. B., and Oliff, A. The potential of farnesyltransferase inhibitors as cancer therapeutics. Annu. Rev. Pharmacol. Toxicol., 37: 143-166, 1997.
27. Norgaard, P., Law, B., Mays, D., Pietenpol, J. A., Kohl, N. E., Oliff, A. I., Poulsen, H. S., and Moses, H. L. Inhibition of cell cycle progression and milogenic signal transducers in vivo by farnesyltransferase inhibitor. Proc. Am. Assoc. Cancer Res., 39: 1839, 1998.
28. Liu, M., Lee, S., Yaremko, B., Chen, J., Dell, J., Nielsen, L., Lipari, P., Ferrari, E., Malkowski, M., Bryant, M. S., Njoroge, F. G., Traveras, A. G., Doll, R. J., Kirschmeier, P., Nomeir, A. A., Kelly, J., Remiszewski, S., Mallams, A. K., Afonso, A., Hollinger, F. P., Cooper, A. B., Liu, Y-T., Rane, D., Girijavallabhan, V., Ganguly, A. K., and Bishop, W. R. SCH66336 an orally bioavailable tricyclic farnesyl protein transferase inhibitor, demonstrates broad and potent in vivo antitumor activity. Proc. Am. Assoc. Cancer Res., 39: 1843, 1998.
29. Przybranowski, S. A., Vincent, P. W., Lathia, C., Hollembaek, J., Quin, J., Shuler, K. R., Dykes, D. J., Sebolt-Leopold, J. S., and Leopold, W. R. In vivo evaluation of farnesyltransferase inhibitor, PD169451. Proc. Am. Assoc. Cancer Res., 39: 1841, 1998.
30. Zujewski, J., Horak, I. D., Woestcnborghs, R., Chiao, J., Cusack, G., Kohler, D., Kremer, A. B., and Cowan, K. H. Phase I trial of farnesyl-transferase inhibitor R115777 in advanced cancer. Proc. Am. Assoc. Cancer Res., 39: 1848, 1998.
31. Vrignaud, P., Bello, A., Bissery, M. C., Jenkins, R., Hasnain, A., Mailliet, P., and Lavelle, F. RPR 130401, a non-peptidomimetic farnesyltransferase inhibitor with in vivo activity. Proc. Am. Assoc. Cancer Res., 39: 1846, 1998.
32. Sinensky, M., and Lutz, R. J. The prenylation of proteins. Bioessays, 14: 25-31, 1992.
33. James, G. L., Goldstein, J. L., Brown, M. S., Rawson, T. E., Somers, T. C., McDowell, R. S., Crowley, C. W., Lucas, B. K., Levinson, A. D., and Marsters, J. C. Benzodiazepine peptidomimeytics: potent inhibitors of ras farnesylation in animal cells. Science (Washington DC), 260: 1937-1942, 1993.
34. Weber, K., Plessman, U., and Traub, P. Maturation of nuclear lamin A involves a specific carboxy-terminal trimming, which removes the polyisoprenylation site from the precursor; implications for the structure of nuclear lamina. FEBS Lett., 257: 411-414, 1989.