Cancer Treatment Reviews
Volume 26, Issue 5 , Pages 319-332 , October 2000

Farnesyl transferase inhibitors: current developments and future perspectives

References 

    REFERENCES
  1. Bos JL. ras oncogenes in human cancer: a review. Cancer Res. 1989;49:4682–4689
  2. Gibbs JB. Ras C-terminal processing enzymes, new drug targets?. Cell. 1991;65:1–4
  3. Gibbs JB, Oliff A, Kohl NE. Farnesyl transferase inhibitors: Ras reseach yields a potential cancer therapeutic. Cell. 1994;77:175–178
  4. Gibbs JB, Kohl NE, Koblan KS. Farnesyl transferase inhibitors and anti-Ras therapy. Breast Cancer Res Treat. 1996;38:75–83
  5. Gibbs JB, Oliff A. The potential of farnesyl transferase inhibitors as cancer chemotherapeutics. Annu Rev Pharmacol Toxicol. 1997;37:143–166
  6. Lowy DR, Willumsen BM. Function and regulation of Ras. Annu Rev Biochem. 1993;62:851–891
  7. Lebowitz PF, Davide JP, Prendergast GC. Evidence that farnesyl transferase inhibitors suppress Ras transformation by interferring with Rho activity. Moll Cell Biol. 1995;15:6613–6622
  8. Prendergast GC. Targeting farnesyl transferase: is Ras relevant?. Am Soc Clin Oncol Ed Book. 1999;22–28
  9. Hara M, Akasaka K, Akinaga S. Identification of Ras farnesyl transferase inhibitors by microbial screening. Proc Natl Acad Sci USA. 1993;90:2281–2285
  10. Tamanoi F. Inhibitors of Ras farnesyltransferases. Trends Biochem Sci. 1993;18:349–353
  11. Ito T, Kawata S, Tamura S. Suppression of human pancreatic cancer growth in BALB/c nude mice by manumycin, a farnesyl protein transferase inhibitor. Jpn J Cancer Res. 1996;87:113–116
  12. Kainamu O, Asano T, Hasegawa M, Isono K. Growth inhibition of human pancreatic cancer by farnesyl transferase inhibitor. Gan To Kagaku Ryoho. 1996;23:1657–1659
  13. Yonemoto M, Satoh T, Arakawa H. J-104,871, a novel farnesyl transferase inhibitor, blocks Ras farnesylation in vivo in a farnesylpyrophosophate-competitive manner. Mol Pharmacol. 1998;54:1–7
  14. Mailliet P, Lelievre E, Chevé M. Synthesis and in-vitro structure-activity relationship of a new promising series of non peptidic protein farnesyl transferase inhibitors. Proc Am Ass Cancer Res. 1997;38:350
  15. Mailliet P, Riou JF, Duchesne M. Benzo[f]perhydroisoindoles: a series of potent and selective inhibitors of the farnesylation of Ki-Ras. Proc Am Ass Cancer Res. 1998;39:270
  16. Vrignaud P, Mailliet P, Bissery MC. Structure activity relationship and in vivo evaluation in a new promising family of nonpeptidomimetic farnesyl transferase inhibitors. Proc Am Ass Cancer Res. 1997;38:350
  17. Vrignaud P, Bello A, Bissery MC. RPR 130401, a non-peptidomimetic farnesyl transferase inhibitor with in vivo activity. Proc Am Ass Cancer Res. 1998;39:270
  18. Vrignaud P, Bissery MC, Maillet P, Lavelle F. In vivo combination of RPR 130401, a non-peptidomimetic farnesyl transferase inhibitor, with chemotherapy. Proc Am Ass Cancer Res. 1999;40:523
  19. Przybranowski SA, Vincent PW, Lathia C. In vivo evaluation of farnesyl transferase inhibitor PD 169451 versus a panel of human tumor xenografts. Proc Am Ass Cancer Res. 1998;39:269
  20. James GL, Goldstein JL, Brown MS. Benzodiazepine peptidomimetics: potent inhibitors of Ras farnesylation in animal cells. Science. 1993;260:1937–1942
  21. James GL, Brown MS, Cobb MH, Goldstein JL. Benzodiaze pine peptidomimetic BZA-5B interrupts the MAP kin- ase activation pathway in H- ras transformed Rat-1 cells, but not in untransformed cells. J Biol Chem. 1994;269:27705–27714
  22. Garcia AM, Rowell C, Ackerman K, Kowalczyk JJ, Lewis MD. Peptidomimetic inhibitors of Ras farnesylation and function in whole cells. J Biol Chem. 1993;268:18415–18418
  23. Cox AD, Garcia AM, Westwick JK. The CAAX peptidomimetic compound B581 specifically blocks farnesylated, but not geranylgeranylated or myristilated oncogenic ras signaling and transformation. J Biol Chem. 1994;269:19203–19206
  24. Nagasu T, Yoshimatsu K, Rowell C, Lewis MD, Garcia AM. Inhibition of human tumor xenograft by treatment with the farnesyl transferase inhibitor B956. Cancer Res. 1995;55:5310–5314
  25. Yoshimatsu K, Nagasu T. Anti tumor activity of farnesyl transferase inhibitor. Gan To Kagaku Ryoho. 1997;24:145–155
  26. Aklilu F, Park M, Goltzman D, Rabbani SA. Induction of parathyroid hormone-related peptide by the ras oncogene: role of Ras farnesylation inhibitors as potential therapeutic agents for hypercalcemia of malignancy. Cancer Res. 1997;57:4517–4522
  27. Kohl NE, Mosser SD, deSolms SJ. Selective inhibition of Ras dependent transformation by a farnesyl transferase inibitor. Science. 1993;260:1934–1937
  28. Kohl NE, Wilson FR, Mosser SD. Protein farnesyltransferase inhibitors block the growth of ras -dependent tumors in nude mice. Proc Natl Acad Sci USA. 1994;91:9141–9145
  29. Omer CA, Kohl NE. CA1A2X competitive inhibitors of farnesyl transferase as anti-cancer agents. Trends in Pharmacol Sci. 1997;18:437–445
  30. Lebowitz PF, Sakamuro D, Prendergast GC. Farnesyltransferase inhibitors induce apoptosis of Ras-transformed cells denied substratum attachment. Cancer Res. 1997;57:708–713
  31. Prendergast GC, Davide JP, Jane deSolms S. Farnesyltransferase inhibition causes morphological reversion of ras -transformed cells by a complex mechanism that involves regulation of the actin cytoskelton. Mol Cell Biol. 1994;14:4193–4204
  32. Lebowitz PF, Davide JP, Prendergast GC. Evidence that farnesyl transferase inhibitors suppress Ras transformation by interfering with Rho activity. Mol Cell Biol. 1995;15:6613–6622
  33. Lebowitz PF, Prendergast GC. Non-Ras targets of farnesyl transferase inhibitors; focus on Rho. Oncogene. 1998;17:1439–1445
  34. Sepp-Lorenzino L, Ma Z, Rands E. A peptidomimetic inhibitor of farnesyl protein transferase blocks the anchorage dependent and -independent growth of human tumor cell lines. Cancer Res. 1995;55:5302–5309
  35. Kohl NE, Omer CA, Conner MW. Inhibition of farnesyltransferase induces regression of mammary and salivary carcinomas in ras transgenic mice. Nat Med. 1995;1:792–797
  36. Mangues R, Corral T, Kohl NE. Antitumor effect of a farnesyl protein transferase inhibitor in mammary and lymphoid tumors overexpressing N-ras in transgenic mice. Cancer Res. 1998;58:1253–1259
  37. Norgaard P, Law B, Joseph H. Treatment with farnesyl protein transferase inhibitor induces regressio of mammary tumors in transforming growth factor (TGF) α and TGF α/ neu transgenic mice by inhibition of mitogenic activity and induction of apoptosis. Clin Cancer Res. 1999;5:35–42
  38. Feldkamp MM, Lau N, Guha A. The farnesyl transferase inhibitor L-744,832 inhibits the growth of astrocytomas through a combination of anti-proliferative, anti-angiogenic and pro-apoptotic activities. Proc Am Ass Cancer Res. 1999;40:523
  39. McGuire TF, Qian Y, Blaskovich MA. CaaX peptidomimetic FTI 244 decreases platelet-derived growth factor tyrosine phosphorylation levels and inhibits stimulation of phosphatidylinositol 3-kinase but not mitogen-activated protein kinase. Biochem Biophys Res Commun. 1995;214:295–303
  40. Sun J, Qian Y, Hamilton AD, Sebti SM. Ras CAAX peptidomimetic FTI 276 blocks tumor growth in nude mice of a human lung carcinoma with K-Ras mutation. Cancer Res. 1995;55:4243–4247
  41. Sun J, Knowles D, Augeri DJ, Rosenberg SH, Hamilton AD, Sebti SM. Antitumor activity of non-thiol containing farnesyl transferase inhibitors. Proc Am Ass Cancer Res. 1998;39:269
  42. Lantry LE, Zhang Z, Sebti S. Chemotherapeutic effect of the farnesyl transferase inhibitor FTI-276 on 4-(methyl-nitrosamino)-1-(3-pyridil)-1-butanone induced tumorigenesis in A/J mouse lung. Proc Am Ass Cancer Res. 1998;39:269
  43. Sun J, Marfurt J, Blaskovich MA. Effective combination therapy with the non-thiol farnesyl transferase inhibitor FTI-2148 and taxol, gemcitabine or cisplatinum for human tumor xenografts in nude mice. Proc Am Ass Cancer Res. 1999;40:522
  44. Moasser MM, Sepp-Lorenzino L, Kohl NE. Farnesyl transferase inhibitors cause enhanced mitotic sensitivity to taxol and epithelones. Proc Natl Acad Sci USA. 1998;95:1369–1374
  45. Bishop WR, Bond R, Petrin J. Novel tricyclic inhibitors of farnesyl protein transferase. Biochemical characterization and inhibition of Ras modification in transfected Cos cells. J Biol Chem. 1995;270:30611–30618
  46. Njoroge FJ, Vibulbhan B, Rane D. Structure activity relationship of 3-substituted n-(pyridinylacetyl)-4-(8-chloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridine-11-ylidene)-piperidine inhibitors of farnesyl protein transferase: design and synthesis of in vivo active antitumor compounds. J Med Chem. 1997;40:4290–4301
  47. Liu M, Chen P, Lee S. SCH 59228, a novel tricyclic inhibitor of farnesyl protein transferase, potently blocks the growth of Ras transformed fibroblasts and human tumor cell lines in nude mice. Proc Am Ass Cancer Res. 1997;38:349
  48. Liu M, Bryant MS, Chen J. Effects of SCH 59228, an orally bioavailable farnesyl protein transferase inhibitor, on the growth of oncogene-transformed fibroblasts and a human colon carcinoma xenograft in nude mice. Cancer Chemother Pharmacol. 1999;43:50–58
  49. Liu M, Lee S, Yaremko B. SCH 66336, an orally bioavailable tricyclic farnesyl protein transferase inhibitor, demonstrates broad and potentin-vivo antitumor activity. Proc Am Ass Cancer Res. 1998;39:270
  50. Liu M, Bryant M, Chen J. Tumor activity of SCH 66336, an orally bioavailable tricyclic inhibitor of farnesyl protein transferase in human tumor xenograft models in wap- ras transgenic mice. Cancer Res. 1998;58:4947–4956
  51. Shi B, Gurnani M, Yaremko B. Enhanced efficacy of the farnesyl protein transferase inhibitor SCH 66336 in combination with paclitaxel. Proc Am Ass Cancer Res. 1999;40:524
  52. End D, Skrzat S, Devine A. R115777, a novel imidazole farnesyl protein transferase inhibitor (FTI); biochemical and cellular effects in H-ras and K-ras dominent systems. Proc Am Ass Cancer Res. 1998;39:270
  53. Smets G, van Eyck N, Devine A, Bowden C, Wouters W, End DW. R115777, a selectice farnesyl protein transferase inhibitor (FTI), induces predominantly apoptotic activity in C32 melanoma tumor xenografts. Proc Am Ass Cancer Res. 1999;40:522
  54. Skrzat S, Bowden C, End D. Interaction of the farnesyl protein transferase inhibitor (FTI) R115777 with cytotoxic chemotherapeutics in vitro and in vivo. Proc Am Ass Cancer Res. 1999;40:523
  55. Ranganathan S, McCauley R, Hudes G. Combined cell cycle and cytotoxic effects of paclitaxel and R115777, a specific inhibitor of p21 ras function and protein farnesylation in human prostate and breast carcinoma cell lines. Proc Am Ass Cancer Res. 1999;40:523
  56. Patel DV, Schmidt RJ, Biller SA, Gordon EM, Robinson SS, Manne V. Farnesyl diphosphate-based inhibitors of Ras farnesyl protein transferase. J Med Chem. 1995;38:2906–2921
  57. Patel D, Gordon E, Schmidt R. Phosphinyl-acid based bisubstrate analog inhibitors of Ras farnesyl protein transferase. J Med Chem. 1995;38:435–442
  58. Manne V, Yan N, Carboni J. Bisubstrate inhibitors of farnesyl transferase: a novel class of specific inhibitors of ras transformed cells. Oncogene. 1995;10:1763–1779
  59. Britten CD, Rowinsky E, Yao S-L. The farnesyl protein transferase (FPTase) inhibitor L-778,123 in patients with solid cancers. Proc Am Soc Clin Oncol. 1999;18:155a
  60. Adjei AA, Erlichman Ch, Davis JN. A phase I and pharmacologic study of the farnesyl protein transferase (FPT) inhibitor SCH 66336 in patients with locally advanced or metastatic cancer. Proc Am Soc Clin Oncol. 1999;18:156a
  61. Eskens F, Awada A, Verweij J, Cutler DL, Hanauske A, Piccart M. Phase I and pharmacologic study of continuous daily oral SCH 66336, a novel farnesyl transferase inhibitor, in patients with solid tumors. Proc Am Soc Clin Oncol. 1999;18:156a
  62. Hurwitz HI, Colvin OM, Petros WP. Phase I and pharmacokinetic study of SCH 66336, a novel FPTI, using a 2-week on, 2-week off schedule. Proc Am Soc Clin Oncol. 1999;18:156a
  63. Awada A, Eskens F, Piccart MJ. A clinical; pharmacodynamic and pharmacokinetic phase I study of SCH 66336 (SCH), an oral inhibitor of the enzyme farnesyl transferase, given once daily in patients with solid tumors. Clin Cancer Res. 1999;5:3733s
  64. Zujewski J, Horak ID, Bol C. Phase I and pharmacokinetic study of farnesyl transferase inhibitor R1157777 in advanced cancer. Proc Am Soc Clin Oncol. 1999;18:192a
  65. Hudes G, Schol J, Baab A. Phase I clinical and pharmacokinetic trial of the farnesyl transferase inhibitor R115777 on a 21-day dosing schedule. Proc Am Soc Clin Oncol. 1999;18:156a
  66. Schellens J, De Klerk G, Swart M. Phase I and pharmacologic study with the novel farnesyl transferase inhibitor (FTI) R115777. Proc Am Soc Clin Oncol. 2000;19:184a
  67. Peeters M, van Cutsem H, Marsé H, Palmer P, Walraven V, Willems L. Phase I combination trial of the farnesyl transferase inhibitor (FTI) R115777 with a 5FU/LV regimen in advanced colorectal and pancreatic cancer. Proc Am Soc Clin Oncol. 1999;18:223a
  68. Khosravi-Far R, Der CJ. The Ras signal transduction pathway. Cancer Met Rev. 1994;13:67–89
  69. Rowinsky EK, Windle JJ, Von Hoff DD. Ras protein farnesyl transferase: A strategic target for anticancer therapeutic development. J Clin Oncol. 1999;17:3631–3652

PII: S0305-7372(00)90187-7

doi: 10.1053/ctrv.2000.0187

Cancer Treatment Reviews
Volume 26, Issue 5 , Pages 319-332 , October 2000

Article Tools