31
Views
19
CrossRef citations to date
0
Altmetric
Review

Protein farnesyltransferase inhibitors

&
Pages 163-178 | Published online: 02 Mar 2005

Bibliography

  • PARKIN DM: Global cancer statistics in the year 2000. Lancet Oncol (2001) 2(9):533–543.
  • EINHORN EH: Testicular cancer: an oncological success story. Clip. Cancer Res. (1997) 3(12):2630–2632.
  • BARBACID M: Ras genes. Ann. Rev Biochem. (1987) 56:779–827.
  • SHIH C, PADHY LC, MURRAY M, WEINBERG RA: Transforming genes of carcinomas and neuroblastomas introduced into mouse fibroblasts. Nature (1981) 290(5803):261–264.
  • ADAMS JM, CORY S: Transgenic models of tumor development. Science (1991) 254(5035):1161–1167.
  • BOS JL, FEARON ER, HAMILTON SR et al.: Prevalence of ras gene mutations in human colorectal cancers. Nature (1987) 327(6120):293–297.
  • VISVANATHAN KV, POCOCK RD, SUMMERHAYES IC: Preferential and novel activation of H-ras in human bladder carcinomas. Oncogene Res. (1988) 3(1):77–86.
  • BEAUPRE DM, KURZROCK R: RAS and leukemia: from basic mechanisms to gene-directed therapy. Clio. Oncol (1999) 17(3):1071–1079.
  • •Overview of the literature linking Ras signalling to leukaemia.
  • CLARK GJ, DER CJ: Ras protein activation in human malignancy. In: Cellular Cancer. Markers CT, Garret T & Sell S (Eda), Humana Press, Totowa, USA (1995):17–52.
  • CLARK GJ, DER CJ: Aberrant function of the Ras signal transduction pathway in human breast cancer. Breast Cancer Res. Treat. (1995) 35(1):133–144.
  • ••Important summary describing the role ofRas signalling pathways in breast cancer.
  • GOLDSTEIN JL, BROWN MS: Regulation of the mevalonate pathway. Nature (1990) 343(6257):425–430.
  • CASEY PJ, THISSEN JA, MOOMAW JF: Enzymatic modification of proteins with a geranylgeranyl isoprenoid. Proc. Natl. Acad. Sci. USA (1991) 88(19):8631–8635.
  • YOKOYAMA K, GOODWIN G, GHOMASHCHI F et al: A protein geranylgeranyl transferase from bovine brain: implications for protein prenylation specificity. Proc. Natl. Acad. Sci. USA (1991) 88:5302–5306.
  • CLARKE S: Protein isoprenylation and methylation at carboxyl-terminal cysteine residues. Ann. Rev Biochem. (1992) 61:355–386.
  • LEEVERS SJ, PATERSON HF, MARSHALL CJ: Requirement for Ras in Raf activation is overcome by targeting Raf to the plasma membrane. Nature (1994) 369(6479):411–414.
  • MARSHALL CJ: Cell signalling. Raf gets it together. Nature (1996) 383(6596):127–128.
  • KODAKI T, WOSCHOLSKI R, HALLBERG B, RODRIGUEZ-VICIANA P, DOWNWARD J, PARKER PJ: The activation of phosphatidylinositol 3-kinase by Ras. Carr: Biol. (1994) 4(9):798–806.
  • KENNEDY SG, WAGNER AJ, CONZEN SD et al: The P13-kinase/Akt signaling pathway delivers an anti-apoptotic signal. Genes Dev. (1997) 11(6):701–713.
  • LANGE-CARTER CA, PLEIMAN CM, GARDNER AM, BLUMER KJ, JOHNSON GL: A divergence in the MAP kinase regulatory network defined by MEK kinase and Raf. Science (1993) 260(5106):315–319.
  • RIDLEY AJ, HALL A: The small GTP-binding protein rho regulates the assembly of focal adhesions and actin stress fibers in response to growth factors. Cell (1992) 70(3):389–399.
  • OSTEROP AP, MEDEMA RH, VD ZON GC, BOS JL, MOLLER W, MAASSEN JA: Epidermal-growth-factor receptors generate Ras GTP more efficiently than insulin receptors. Eur. Biochem. (1993) 212(2):477–482.
  • KATO K, COX AD, HISAKA MM, GRAHAM SM, BUSS JE, DER CJ: Isoprenoid addition to Ras protein is the critical modification for its membrane association and transforming activity. Proc. Nati Acad. Sci. USA (1992) 89(14):6403–6407.
  • LEONARD D: Ras farnesyltransferase: a new therapeutic target. I Med. Chem. (1997) 40(19):2971–2990.
  • ROWINSKY EK, WINDLE JJ, VON HOFF DD: Ras protein farnesyltransferase: a strategic target for anticancer therapeutic development.j Clin. Oncol (1999) 17(11):3631–3652.
  • ••Comprehensive review of the molecularbiology of Ras and FT.
  • SEPP-LORENZINO L, MA Z, RANDS E et al.: A peptidomimetic inhibitor of farnesyl:protein transferase blocks the anchorage-dependent and -independent growth of human tumor cell lines. Cancer Res. (1995) 55(22):5302–5309.
  • KOHL NE, OMER CA, CONNER MW et al.: Inhibition of farnesyltransferase induces regression of mammary and salivary carcinomas in ras transgenic mice. Nat. Med. (1995) 1(8):792–797.
  • QIAN Y, BLASKOVICH MA, SALEEM M et al: Design and structural requirements of potent peptidomimetics inhibitors of p21 ras farnesyltransferase. Biol. Chem. (1994) 269(17):12410–12413.
  • MANNE V, YAN N, CARBONI JM et al: Bisubstrate inhibitors of farnesyltransferase: a novel class of specific inhibitors of ras transformed cells. Oncogene (1995) 10(9):1763–1779.
  • LAVELLE F: American Association for Cancer Research 1998: promises and prospects for the next century. Expert Opin. Investig. Drugs (1998) 7(6):1015–1021.
  • END DW, SMETS G, TODD AV: Characterization of the antitumor effects of the selective farnesyl protein transferase inhibitor R115777 in vivo and in vitro. Cancer Res. (2001) 61(1):131–137.
  • •Preclinical summary of antiturnour effects of R115777.
  • COX AD, DER J: Farnesyl transferase inhibitors and cancer treatment: targeting simply ras? Biochem. Biophys. Acta (1997) 1333(1):F51–F71.
  • •Review outlining the evidence that FTIs target proteins other than Ras.
  • LIU M, BRYANT MS, CHEN J et al: Antitumor activity of SCH 66336, an orally bioavailable tricyclic inhibitor of farnesyl protein transferase, in human tumor xenograft models and wap-ras transgenic mice. Cancer Res. (1998) 58(21):4947–4956.
  • •Preclinical summary of antiturnour activity of SCH66336.
  • WHYTE DB, KIRSCHMEIER P, HOCKENBERRY TN et al.: K-ras and N-ras are geranylgeranylated in cells treated with farnesyl protein transferase inhibitors. Biol. Chem. (1997) 272(22):14459–14464.
  • PRENDERGAST GC, DAVIDE JP, DE SOLMS SJ et al.: Farnesyltransferase inhibition causes morphological reversion of ras-transformed cells by a complex mechanism that involves regulation of the actin cytoskeleton. Ma Cell Biol. (1994) 14(6):4193–4202.
  • MIQUEL K, PRADINES A, SUN J et al.: GGTI-298 induces GO- G1 block and apoptosis whereas FTI-277 causes G2-M enrichment in A549 cells. Cancer Res. (1997) 57(10):1846–1850.
  • SEPP-LORENZINO L, ROSEN N: A farnesyl-protein transferase inhibitor induces p21 expression and G1 block in p53 wild-type tumor cells. J. Biol. Chem. (1998) 273(32):20243–20251.
  • ASHAR HR, ARMSTRONG L, JAMES LJ et al.: Biological effects and mechanism of action of farnesyl transferase inhibitors. Chem. Res. Toxicol (2000) 13:949–952.
  • DU W, LIU A, PRENDERGAST GC: Activation of the PI3'K-AKT pathway masks the proapoptotic effects of farnesyltransferase inhibitors. Cancer Res. (1999) 59(17):4208–4212.
  • ••Elegant data on the effect of the PI3Kpathway on the antitumour properties of FTIs.
  • KELLAND LR, SMITH V, VALENTI M et al.: Preclinical antitumor activity and pharmacodynamic studies with the farnesyl protein transferase inhibitor R115777 in human breast cancer. Clin. Cancer Res (2001) 7(11):3544–3550.
  • •Preclinical evidence of in vivo activity of FTIs in a breast cancer.
  • ASHAR HR, JAMES LJ, GRAY K et al:Farnesyl transferase inhibitors block the farnesylation of CENP-E and CENP-F and alter the association of CENP-E with the microtubules. Biol. Chem. (2000) 275(39):30451–30457.
  • WOOD KW, SAKOWICZ R, GOLDSTEIN LS, CLEVELAND DW: CENP-E is a plus end-directed kinetochore motor required for metaphase chromosome alignment. Cell (1997) 91(3):357–366.
  • LIAO H, WINKFEIN RJ, MACK G, RATTNER JB, YEN TJ: CENP-F is a protein of the nuclear matrix that assembles onto kinetochores at late G2 and is rapidly degraded after mitosis. Cell Biol. (1995) 130(3):507–518.
  • YAO X, ANDERSON KL, CLEVELAND DW: The microtubule-dependent motor centromere-associated protein E (CENP-E) is an integral component of kinetochore corona fibers that link centromeres to spindle microtubules. Cell Biol. (1997) 139(2)435–447.
  • DU W, PRENDERGAST GC: Geranylgeranylated RhoB mediates suppression of human tumor cell growth by farnesyltransferase inhibitors. Cancer Res. (1999) 59(21):5492–5496.
  • SUN J, QIAN Y, HAMILTON AD, SEBTI SM: Both farnesyltransferase and geranylgeranyltransferase I inhibitors are required for inhibition of oncogenic K-Ras prenylation but each alone is sufficient to suppress human tumor growth in nude mouse xenografts. Oncogene (1998) 16(11):1467–1473.
  • JIANG K, COPPOLA D, CRESPO NC et al.: The phosphoinositide 3-0H kinase/ AKT2 pathway as a critical target for farnesyltransferase inhibitor-induced apoptosis. Mol. Cell Biol. (2000) 20(1):139–148.
  • NAGASU T, YOSHIMATSU K, ROWELL C, LEWIS MD, GARCIA AM: Inhibition of human tumor xenograft growth by treatment with the farnesyl transferase inhibitor B956.Cancer Res. (1995) 55(22):5310–5314.
  • ADJEI AA, ERLICHMAN C, DAVIS JN et al.: A Phase I trial of the farnesyl transferase inhibitor 5CH66336: evidence for biological and clinical activity. Cancer Res. (2000) 60(7):1871–1877.
  • •First full paper of Phase I with SCH66336 using prelamin A from buccal mucosal cells as a PD marker.
  • ESKENS FA, AWADA A, CUTLER DL et al.: Phase I and pharmacokinetic study of the oral farnesyl transferase inhibitor SCH 66336 given twice daily to patients with advanced solid tumors. J. Clin. Oncol (2001) 19(4):1167–1175.
  • HURWITZ H, COLVIN OM, PETROS W et al.: 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:A599.
  • AWADA A, ESKENS FA, PICCART M et al.: A Phase I and pharmacological study of the oral farnesyl transferase inhibitor SCH 66336 given once daily to patients with advanced solid tumours. Ear: J. Cancer (2001) 38(17):2272–2278.
  • LIST A, CORTES J, DEANGELO D et al.:Phase I study of continuous oral administration of lonafarnib (SCH 66336) in patients with advanced myelodysplastic syndrome (MDS), acute myeloid leukaemia (AML), chronic myeloid leukaemia (CML), chronic myleoid leukaemia blast crisis (CML-BC) and acute lymphoblastic leukaemia (ALL). Cancer Invest. (2002) 21\(Suppl. 1):A67.
  • WINQUIST E, MOORE MJ, CHI K et al: NCIC CTG IND.128: a Phase II study of a farnesyl transferase inhibitor (5CH66336) in patients with unresectable or metastatic transitional cell carcinoma of the urothelial tract failing prior chemotherapy. Proc. Am. Soc. Clin. Oncol. (2001) 20:A785.
  • LERSCH C, VAN CUTSEM E, AMADO R et al.: Randomized Phase II study of SCH 66336 and gemcitabine in the treatment of metastatic adenocarcinoma of the pancreas. Proc. Am. Soc. Clin. Oncol. (2001) 20:A680.
  • SHARMA S, KEMENY N, KELSEN DP et al.: A Phase II trial of farnesyl protein transferase inhibitor SCH 66336, given by twice-daily oral administration, in patients with metastatic colorectal cancer refractory to 5-fluorouracil and irinotecan. Ann. Oncol. (2002) 13:1067–1071.
  • SHI B, YAREMKO B, HAJIAN G et al.:The farnesyl protein transferase inhibitor SCH 66336 synergizes with taxanes M vitro and enhances their antitumour activity M vivo. Cancer Chemother. Pharmacol. (2000) 46:387–393.
  • •Important data on the synergism of FTIs with taxanes.
  • HURWITZ H, AMADO R, PRAGER D et al.: Phase I pharmocokinetic trial of the farnesyl transferase inhibitor SCH 66336 plus gemcitabine in advanced cancer. Proc. Am. Soc. Clin. Oncol. (2000) 19:A717.
  • KHURI FR, GLISSON B, MEYERS ML et al.: Phase I study of farnesyl transferase inhibitor (FTI) 5CH66336 with paclitaxel in solid tumors: dose finding, pharmacokinetics, efficacy/safety. Proc. Am. Soc. Clin. Oncol. (2000) 19:A799.
  • PIERSON AS, HOLDEN SN, BASCHE M et al: A Phase I pharmacokinetic (PK) and biological study of the farnesyl transferase inhibitor (FTI) sarasar (SCH 66336), cisplatin and gemcitabine in patients with advanced solid tumours. Proc. Am. Soc. Clin. Oncol. (2002) 21:A365.
  • ZAKNEON SL, CRAWFORD J, SHEPHERD F et al.: Phase I study of oral lonafarnib plus docetaxel as second-line treatment for advanced solid tumors. Proc. Am. Soc. Clin. Oncol. (2002) 21:A2136.
  • SPRAGUE E, VOLKES EE, GARLAND LL et al.: Phase I study of continuous lonafarnib plus paclitaxel and carboplatin in refractory or advanced solid tumors. Proc. Am. Soc. Clin. Oncol. (2002) 21:A1920.
  • LIPTON A, READY N, BUKOWSKI RM et al.: Phase I study of continuous oral lonafarnib plus weekly paclitaxel for advanced cancer. Proc. Am. Soc. Clin. Oncol. (2002) 21:A364.
  • KIM ES, KIES MS, FOSSELLA FV et al.: A Phase I/II study of the farnesyl transferase inhibitor (FTI) SCH 66336 with paclitaxel in patients with solid tumors. Proc. Am. Assoc. Cancer Res. (2002) 43:A2735.
  • PUNT CJ, VAN MAANEN L, BOL CJ, SEIFERT WF, WAGENER DJ: Phase land pharmacokinetic study of the orally administered farnesyl transferase inhibitor R115777 in patients with advanced solid tumors. Anticancer Drugs (2001) 12(3):193–197.
  • HUDES GR, SCHOL J, BAAB J et al: Phase I clinical and pharmacokinetic trial of the farnesyltransferase inhibitor R115777 on a 21-day dosing schedule. Proc. Am. Soc. Clin. Oncol. (1999) 18:A601.
  • CRUL M, DE KLERK G, SWART M et al.: Phase I clinical and pharmacologic study of chronic oral administration of the farnesyl protein transferase inhibitor R115777 in advanced cancer.' Clin. Oncol. (2002) 20:2726–2735.
  • NAKAGAWA K, YAMAMOTO N, NISHIO K et al: A Phase I, pharmacokinetic (PK) and pharmacodynamic (PD) study of the farnesyl transferase inhibitor (FTI) R115777 in Japanese patients with advanced non-hematological malignancies. Proc. Am. Soc. Clin. Oncol. (2001) 20:A317.
  • ZUJEWSKI J, HORAK ID, BOL CJ et al: Phase I and pharmacokinetic study of farnesyl protein transferase inhibitor R115777 in advanced cancer. J. Clin. Oncol. (2000) 18(4):927–941.
  • •First full paper of Phase I study with R115777.
  • WIDEMANN BC, SALZER WL, ARCECI RJ et al.: Phase I trial of R115777, an oral farnesyltransferase (FTase) inhibitor, in children with refractory solid tumors and neurofibromatosis Type I (NF1). Proc. Am. Soc. Clin. Oncol. (2001) 20:A1467.
  • KUHN JG, PRADOS M, ROBINS HI et al.: Phase I trial of R115777 (Zarnestra) in patients with recurrent malignant glioma taking enzyme inducting antiepileptic drugs (EIAED). A North American Brain Tumor Consortium (NABTC) report. Proc. Am. Soc. Clin. Oncol. (2002) 21:A342.
  • KARP JE, LANCET JE, KAUFMANN SH et al.: Clinical and biologic activity of the farnesyltransferase inhibitor R115777 in adults with refractory and relapsed acute leukemias: a Phase I clinical-laboratory correlative trial. Blood (2001) 97(11):3361–3369.
  • •Phase I evidence of activity for FTIs in haematological malignancy.
  • KURZROCK R, WILSON EF, SEBTI SM: Clinical activity and inhibition of protein farnesylation in FTI-R115777 treated patients with myelodysplastic syndrome (MDS). Proc. Am. Assoc. Cancer Res. (2002) 43:A4959.
  • GOTLIB J, DUGAN K, KATAMNENI U et al.: Phase I/II study of ZarnestraTM (farnesyltransferase inhibitor R115777) in patients with myeloproliferative disorders (MPDs): preliminary results. Proc. Am. Soc. Clin. Oncol. (2002) 21:A14.
  • LANCET J, ROSENBLATT J, LIESVELD D et al.: Use of farnesyl transferase inhibitor R115777 in relapsed and refractory acute leukemias: preliminary results of a Phase I trial. Proc. Am. Soc. Clin. Oncol. (2000) 19:A5B.
  • PATNAIK A, ECKHARDT SG, IZBICKA E et al.: Administration of biologically and clinically relevant doses of the farnesyl transferase inhibitor R115777 and gemcitabine are feasible without pharmacokinetic (PK) interactions: a Phase I and PK study. Clin. Cancer Res. (2000) 6(Suppl.):A255.
  • HOLDEN SN, ECKHARDT SG, FISHERS et al: A Phase I pharmacokinetic (PK) and biological study of the farnesyl transferase inhibitor (FTI) R115777 and capecitabine in patients (PTS) with advanced solid malignancies. Proc. Am. Soc. Clin. Oncol. (2001) 20:A316.
  • VERSLYPE C, VAN STEENBURGEN W, HUMBLET Y et al.: Phase I trial of 5-FU/ LV in combination with the farnesyltransferase inhibitor (FTI) R115777.Proc. Am. Soc. Clin. Oncol. (2001) 20:A681.
  • PEETERS M, VAN CUTSEM E, MARSE H et al.: Phase I combination trial of the farnesyltransferase inhibitor R-115777 with a 5-FU/LV regimen in advanced colorectal or pancreatic cancer. Proc. Am. Soc. Clin. Oncol. (1999) 18:A859.
  • PICCART GEBHART MJ, BRANLE F, DE VARIOLA D et al.: A Phase I, clinical and pharmacokinetic (PK) trial of the farnesyl transferase inhibitor (FTI) R115777 + docetaxel: a promising combination in patients (pts) with solid tumors. Proc. AM. Soc. Clin. Oncol. (2001) 20:A318.
  • ADJEI AA, ERLICHMAN C, MARKS RS et al.: A Phase I trial of the farnesyltransferase inhibitor R115777, in combination with gemcitabine and cisplatin in patients with advanced cancer. Proc. Am. Soc. Clin. Oncol. (2001) 20:A320.
  • VERWEIJ J, KEHRER DFS, PLANTING A et al.: Phase I trial of irinotecan in combination with the farnesyl transferase inhibitor (FTI) R115777.Proc. Am. Soc. Clin. Omni (2001) 20:A319.
  • SCHWARTZ G, ROWINSKY EK, RHA SY et al.: A Phase I, pharmacokinetic and biologic correlative study of RU 5777 and trastuzumab (Herceptin) in patients with advanced cancer. Proc. Am. Soc. Clin. Omni (2001) 20:A322.
  • LIEBES L, HOCHSTER H, SPEYER J et al.: Enhanced myelosuppression of topotecan when combined with the farnesyl transferase inhibitor R115777: a Phase I and pharmacodynamic study. Proc. Am. Soc. Clin. Omni (2001) 20:A321.
  • PATNAIK A, IZBICKA E, ECKHARDT SG et al.: Inhibition of HDJ2 protein farnesylation in peripheral blood mononuclear cells as a pharmacodynamic endpoint in a Phase I study of R115777 and gemcitabine. Proc. Am. Assoc. Cancer Res. (2001) 42:A2682.
  • JOHNSTON SR, HICKISH T, HOUSTON S et al.: Efficacy and tolerability of two dosing regimens of R115777 (Zarnestra), a farnesyl transferase inhibitor, in patients with advanced breast cancer. Proc. Am. Soc. Clin. Omni (2002) 21:A138.
  • CLOUGHESY TF, KUHN J, WEN P et al.: Phase II trial of R115777 (Zarnestra) in patients with recurrent glioma not taking enzyme inducing antiepileptic drugs (EIAED). A North American Brain Tumor Consortium (NABTC) report. Proc. Am. Soc. Clin. Oncol. (2002) 21:A317.
  • ADJEI AA, MAUER A, MARKS R et al.: A Phase II study of the farnesyltransferase inhibitor RU 5777 in patients with advanced non-small cell lung cancer. Proc. Am. Soc. Clin. Oncol. (2002) 21:A1157.
  • HEYMACH JV, DE PORR P, DE VORE III RF et al.: Phase II study of the farnesyl transferase inhibitor (FTI) R115777 (Zarnestra' l in patients with relapsed small cell lung cancer (SCLC). Proc. Am. Soc. Clin. Oncol. (2002) 21:A1275.
  • MACDONALD JS, CHANSKY K, WHITEHEAD R et al: A Phase II study of farnesyl transferase inhibitor R115777 in pancreatic cancer: a Southwest Oncology Group (SWOG) study. Proc. Am. Soc. Clin. Oncol. (2002) 21:A548.
  • COHEN SJ, HO L, RANGANATHAN S et al.: Phase II And pharmacodynamic trial of the farnesyltransferase inhibitor R115777 as initial therapy in patients with metastatic pancreatic adenocarcinoma. Proc. Am. Soc. Clin. Oncol. (2002) 21:A545.
  • HAROUSSEAU JL, STONE R, THOMAS X et al.: Interim results from a Phase II study of R115777 (Zarnestra TM) in patients with relapsed and refractory acute myelogenous leukaemia. Proc. Am. Soc. Clin. Oncol. (2002) 21:A1056.
  • ALSINA M, OVERTON R, BELLE N et al.: Farnesyl transferase inhibitor FTI-R115777 is well tolerated, induces stabilization of disease and inhibits farnesylation and oncogenic/tumor survival pathways in patients with advanced multiple myeloma. Proc. Am. Assoc. Cancer Res. (2002) 43:A4960.
  • CUNNINGHAM D, DE GRAM ONT A, SCHEITHAUER W et al.: Randomized double-blind placebo controlled trial of the farnesyltransferase inhibitor R-115777 (Zarnestra) in advanced refractory colorectal cancer. Proc. Am. Soc. Clin. Oncol. (2002) 21:A502.
  • VAN CUTSEM E, KARASEK P, OETTLE H et al.: Phase III trial comparing gemcitabine + R115777 (ZarnestraTM) versus gemcitabine + placebo in advanced pancreatic cancer (PC). Proc. Am. Soc. Clin. Oncol. (2002) 21:A517.
  • ROSE WC, LEE FYF, FAIRCHILD CR et al.: Preclinical antitumour activity of BMS-214662, a highly apoptotic and novel farnesyltransferase inhibitor. Cancer Res. (2001) 61:7507–7517.
  • •Predinical summary of the antiturnour properties of BMS-214,662.
  • RYAN DP, EDER J, SUPKO JG et al.: Phase I clinical trial of the farnesyltransferase inhibitor BMS-214662 in patients with advanced solid tumours. Proc. Am. Soc. Clin. Oncol. (2000) 19:A720.
  • SONNICHSEN D, DAMLE B, MANNING J et al.: Pharmacokinetics and pharmacodynamics of the farnesyltransferase inhibitor BMS-214662 in patients with advanced solid tumours. Proc. Am. Soc. Clin. Omni (2000) 19:A691.
  • TABERNERO J, MARMON I, ALBANELL J et al.: A Phase I dose-escalation study of the farnesyltransferase inhibitor BMS-214662 administered as continuous weekly 1-hour infusion in patients with advanced solid tumours. Clin. Cancer Res. (2000) 6(Suppl.):A532.
  • vol M, TABERNERO J, COOPER MR et al.: A Phase I study of the farnesyltransferase inhibitor BMS-214662 administered as a weekly 1-hour infusion in patients with advanced solid tumours; clinical findings. Proc. Am. Soc. Clin. Oncol. (2001) 20:A312.mo. KIM KB, SHIN D, SUMMEY CC et al: Phase I study of farnesyltransferase inhibitor BMS-214662 in solid tumours. Proc. Am. Soc. Clin. Oncol. (2001) 20:A313.
  • CORTES J, KURZROCK R, O'BRIEN S et al.: Phase I study of a farnesyl transferase inhibitor BMS-214662 in patients with refractory or relapsed acute leukaemias. Blood(2001) 98(594a):A2489.
  • CAMACHO LH, SOIGNET S, PEZZULLI S et al.: Dose escalation study of oral farnesyltransferase inhibitor BMS-214662 in patients with solid tumours. Proc. Am. Soc. Clin. Omni (2001) 20:A311.
  • TABERNO J, ALBANELL J, ROJO F et al.: A Phase I pharmacokinetic and serial tumour and PBMC pharmacodynamic study of weekly 24-infusion BMS-214662, a farnesyltransferase inhibitor in patients with advanced solid tumours. Clin. Cancer Res. (2001) 7(3775s):A604.
  • ZHU AX, SUPKO JG, RYAN DP et al: A Phase I clinical, pharmacokinetic and pharmacodynamic study of the farnesyltransferase inhibitor BMS-214662 given as a 24 hour continuous intravenous infusion once weekly x 3 in patients with advanced solid tumours. Proc. Am. Soc. Clin. Oncol. (2002) 21:A366.
  • BAILEY HH, MARNOCHA R, ARZOOMANIAN R et al: Phase I trial of weekly paclitaxel and BMS-214662 in patients with advanced solid tumours. Proc. Am. Soc. Clin. Omni (2001) 20:A314.
  • MACKAY HJ, HOEKSTRA R, ESKENS F et al.: A Phase I dose escalating study of BMS-214662 in combination with cisplatin in patients with advanced solid tumours. Proc. Am. Soc. Clin. Oncol. (2001) 20:A315.
  • DY GK, BRUZEK LM, CROGHAN GA et al.: A Phase I trial of the novel farnesyl protein transferase inhibitor BMS-214662 in combination with paclitaxel and carboplatin in patients with advanced cancer. Proc. Am. Assoc. Cancer Res. (2002) 43:A2736.
  • BRITTEN CD, ROWINSKY EK, YAO SL et al.: The farnesyl transferase (FPTase) inhibitor L-778,123 in patients with solid cancers. Proc. Am. Soc. Clin. Oncol. (1999) 18:A597.
  • BRITTEN CD, ROWINSKY EK, SOIGNET S et al.: A Phase I and pharmacological study of the farnesyl protein transferase inhibitor L-778,123 in patients with solid malignancies. Clin. Cancer Res. (2001) 7(12):3894–3903.
  • GUPTA AK, BAKANAUSKASV, CERMIGLIA GJ et al: The ras radiation resistance pathway. Cancer Res. (2001) 61(10):4278–4282.
  • COHEN-JONATHAN E, EVANS SM, KOCK CJ et al.: The farnesyltransferase inhibitor L744,832 reduces hypoxia in tumors expressing activated H-ras. Cancer Res. (2001) 61(5):2289–2293.
  • HAHN SM, BERNHARD EJ, REGINA W et A Phase I trial of the farnesyltransferase inhibitor L-778,123 and radiotherapy for locally advanced lung and head and neck cancer. Clin. Cancer Res. (2002) 8:1065–1072.
  • •First report of a clinical trial of FTIs in combination with radiotherapy.
  • BOLICK SC, CAMPBELL K, HAMILTON A et al.: Myeloma cells with activated N-Ras are sensitive to FTI-227.Proc. Am. Assoc. Cancer Res. (1999) 40:A832.
  • DELARUE FL, ADNANE J, BIZOUARN F et al.: RhoB is transcriptionally induced by farnesyltransferase and geranylgeranyltransferae inhibitors: induction of RhoB does not correlate with human cancer cell growth inhibition. Proc. Am. Assoc. Cancer Res. (2002) 43:A1671.
  • NG SSW, TSAO MS, HEADLEY DW. Inhibition of the phosphatidylinositide 3-kinase/protein kinase B cell survival pathway enhances gemcitabine toxicity in human pancreatic cancer cells. Proc. Am. Assoc. Cancer Res. (2000) 41:A454.
  • BARRET JM, MAHE A, ETIEVANT C, HILL BT: Effects on human A549 non-small cell lung cancer cells of the protein farnesyltransferase inhibitors, FTI-277, 5CH66336 or L778,123 in combination with DNA-damaging anticancer drugs. Proc. Am. Assoc. Cancer Res. (2002) 43:A4670.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.