Role of farnesyltransferase inhibitors in hematologic malignancies

References

• Lowenberg B, Downing JR, Burnett A. Medical progress: acute myeloid leukemia. NEngif Med. 341(14), 1051–1062 (1999).
   PubMed Web of Science ®Google Scholar
• Cheson BD, Bennett JM, Kopecky KJ et al Revised recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. j Gun. 21(24), 4642–4649 (2003).
   Google Scholar
• Rowe JM, Neuberg D, Friedenberg W et al A Phase III study of three induction regimens and of priming with GM-CSF in older adults with acute myeloid leukemia: a trial by the Eastern Co-operative Oncology Group. Blood 103(2), 479–485 (2004).
   PubMed Web of Science ®Google Scholar
• Mayer RJ, Davis RB, Schiffer CA et al Intensive postremission chemotherapy in adults with acute leukemia. N Engl. I Med. 331(14), 896–903 (1994).
   Google Scholar
• Cassileth PA, Harrington DP, Appelbaum FR et al Chemotherapy compared with autologous or allogeneic bone marrow transplantation in the management of acute myeloid leukemia in first remission. N. Engl. Med. 339(23), 1649–1656 (1998).
   Google Scholar
• Huang ME, Ye YC, Chen SR et al All-trans retinoic acid with or without low dose cytosine arabinoside in acute promyelocytic leukemia. Report of 6 cases. Chin. Med. flgT1.)100(12), 949–953 (1987).
   Google Scholar
• •Report of the first cases of acute promyelocytic leukemia treated with all-trans retinoic acid.
   Google Scholar
• Warrell RP, de The H, Wang ZY, Degos L. Acute promyelocytic leukemia. N. Engl. Med. 329(3), 177–189 (1993).
   Google Scholar
• Fenaux P, Chastang C, Chevret S et al A Randomized comparison of all transretinoic acid (ATRA) followed by chemotherapy and ATRA plus chemotherapy and the role of maintenance therapy in newly diagnosed acute promyelocytic leukemia. B/ooc/94(4), 1192–1200 (1999).
   Google Scholar
• Sievers EL, Larson RA, Stadtmauer EA et al Efficacy and safety of gemtuzumab ozogamicin in patients with CD33-positive acute myeloid leukemia in first relapse.j Clin. Oncol 19 (13), 3244–3254 (2001).
   Google Scholar
• Prendergast GC. Farnesyltransferase inhibitors: antineoplastic mechanism and clinical prospects. CUI7: Opin. Cell Biol. 12(2), 166–173 (2000).
   Google Scholar
• 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. B/ooc/97(11), 3361–3369 (2001).
   Google Scholar
• ••Landmark study on the clinical activity offarnesyltransferase inhibitors (FTIs) in poor-risk myeloid leukemia, and correlative biologic effects.
   Google Scholar
• Liesveld JL, Lancet JE, Rosell KE et al Effects of the farnesyl transferase inhibitor R11577 on normal and leukemic hematopoiesis. Leukemia 17 (9), 1806–1812 (2003).
   Google Scholar
• Haluska P, Dy GK, Adjei AA. Farnesyl transferase inhibitors as anticancer agents. Eur. Cancer38(13), 1685–1700 (2002).
   Google Scholar
• Karp JE, Kaufmann SH, Adjei AA, Lancet JE, Wright JJ, End DW. Current status of clinical trials of farnesyltransferase inhibitors. Gun-. Opin. Oncol 13(6), 470–476 (2001).
   Google Scholar
• Lancet JE, Karp JE. Farnesyl transferase inhibitors in myeloid malignancies. Blood Rev 17(3), 123–129 (2003).
   PubMed Web of Science ®Google Scholar
• ••Description of Ras-mediated signalingpathways in myeloid malignancies. Reviews several clinical trials using FTIs in myeloid disorders.
   Google Scholar
• Baum C, Kirschmeier P Preclinical and clinical evaluation of farnesyltransferase inhibitors. Curt: Oncol Rep. 5(2), 99–107 (2003).
   Google Scholar
• Rowinsky EK, Windle JJ, Von Hoff DD. Ras protein farnesyl-transferase: a strategic target for anticancer therapeutic development. J. Clin. Oncol 17(11), 3631–3652 (1999).
   Google Scholar
• ••Summarizes the role of Ras proteins in thecontrol of normal and transformed cell growth. It also describes the prenylation and farnesylation of proteins, as well as the activation of several effector pathways.
   Google Scholar
• Sinensky M, Lutz RJ. The prenylation of proteins. Bioessays 14(1), 25–31 (1992).
   PubMed Web of Science ®Google Scholar
• Prendergast GC, Oliff A. Farnesyltransferase inhibitors: antineoplastic properties, mechanism of action, and clinical prospects. Semin. Cancer Biol. 10(6), 443–452 (2000).
   PubMed Web of Science ®Google Scholar
• Ashar HR, James L, Gray K et al Farnesyl transferase inhibitors block farnesylation of CENP-E and CENP-F and alter the association of CENP-E with the microtubules. j Biol. Chem. 275 (39), 30451–30457 (2000).
   Web of Science ®Google Scholar
• Casey PJ, Solski PA, Der CJ, Buss JE. p2lras is modified by a famesyl isoprenoid. Proc. Natl Acad. Sri. USA 86(21), 8323–8327 (1989).
   Google Scholar
• •Original work that demonstrated that the addition of a farnesyl moiety (farnesylation) is necessary for processing Ras, and it may be important for membrane localization and transforming activity of Ras proteins.
   Google Scholar
• Lebowitz PF, Casey PJ, Prendergast GC, Thissen JA. Famesyltransferase inhibitors alter prenylation and growth-stimulating function of RhoB. j Biol. Chem. 272(25), 15591–15594 (1997).
   Web of Science ®Google Scholar
• •Description of the importance of FTIs in the prenylation process and their effect on RhoB proteins.
   Google Scholar
• Prendergast GC. Farnesyltransferase inhibitors define a role for RhoB in controlling neoplastic pathophysiology. klistol Ilistopathol 16(1), 269–275 (2001).
   Web of Science ®Google Scholar
• Sebti SM, Der CJ. Opinion: searching for the elusive targets of farnesyltransferase inhibitors. Nature Rev Cancer3(12), 945–951 (2003).
   PubMed Web of Science ®Google Scholar
• ••Review of mechanism of action of FTIs andpossible other targets in addition to Ras.
   Google Scholar
• Lerner EC, Zhang TT, Knowles DB, Qian Y, Hamilton AD, Sebti SM. Inhibition of prenylation of K-Ras, but not H- or N-Ras, is highly resistant to CAAX peptidomimetics and requires both a famesyltransferase and a geranylgeranyltransferase I inhibitor in human tumor cell lines. Oncogene 15(11), 1283–1288 (1997).
   PubMed Web of Science ®Google Scholar
• 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 16(11), 1467–1473 (1998).
   PubMed Web of Science ®Google Scholar
• •Role of alternative prenylation pathway and its impact on Ras oncogenic protein inhibition.
   Google Scholar
• Yonemoto M, Satoh T, Arakawa H et al J-104 871, a novel in a farnesyl pyrophosphate-competitive manner. Mal Pharmacol 54(1), 1–7 (1998).
   Google Scholar
• Russo P, Ottoboni C, Crippa A, Riou JF, O'Connor PM. RPR-115135, a newer non peptidomimetic farnesyltransferase inhibitor, induces Go/G1 arrest only in serum starved cells. Int. j Oncol 18(4), 855–862 (2001).
   Google Scholar
• Patnaik A, Rowinsky EK. Early clinical experience with famesyl protein transferase inhibitors: from the bench to the bedside. In: Farnesyltransferase Inhibitors in Cancer Therapy Setbi SM, Hamilton AD (Eds), Humana Press, NJ, USA, 233–249 (2001).
   Google Scholar
• 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. Gun. Cancer Res. 7(12), 3894–3903 (2001).
   Google Scholar
• Manne V, Yan N, Carboni JM et al Bisubstrate inhibitors of farnesyltransferase: a novel class of specific inhibitors of ras transformed cells. Oncogene10(9), 1763–1779 (1995).
   PubMed Web of Science ®Google Scholar
• James GL, Goldstein JL, Brown MS. Polylysine and CVIM sequences of K-RasB dictate specificity of prenylation and confer resistance to benzodiazepine peptidomimetic in vitro. J. Biol. Chem. 270(11), 6221–6226 (1995).
   Google Scholar
• End DW, Smets G, Todd AV et al. Characterization of the antitumor effects of the selective farnesyl protein transferase inhibitor R115777 in vivo and in vitro. Cancer Res. 61(1), 131–137 (2001).
   Google Scholar
• ••Thorough description of the preclinicaleffects of tipifarnib, the first FTI to reach clinical use.
   Google Scholar
• Lancet JE, Liesveld JL, Ludlow J et al Effects of farnesyl transferase inhibitor R115777 on hematopoiesis, leukemic cell proliferation, and signaling through the mitogen-activated protein kinase (MAPK) pathway. B/ooc/94(10), 149b (1999) (Abstract 3835).
   Google Scholar
• Liu M, Bryant MS, Chen J et al Antitumor activity of 5CH66336, an orally bioavailable tricyclic inhibitor of farnesyl protein transferase, in human tumor xenograft models and wap-ras transgenic mice. Cancer Res. 58(21), 4947–4956 (1998).
   Google Scholar
• •Antineoplastic effects of His in H-Ras transgenic models involve both cell cycle inhibition and p53-independent apoptosis.
   Google Scholar
• Peters DG, Hoover RR, Gerlach MJ et al Activity of the farnesyl protein transferase inhibitor 5CH66336 against BCR/ABL-induced murine leukemia and primary cells from patients with chronic myeloid leukemia. B/ooc/97(5), 1404–1412 (2001).
   Google Scholar
• •FTIs, as a single agents, can target the Bcr-Abl oncoprotein. Provides rationale for clinical trials of FTI use in chronic myeloid leukemia (CML), including imatinib-resistant patients.
   Google Scholar
• Reichert A, Heisterkamp N, Daley GQ, Groffen J. Treatment of BcriAbl-positive acute lymphoblastic leukemia in P190 transgenic mice with the farnesyl transferase inhibitor 5CH66336. Blooc197 (5), 1399–1403 (2001). 854
   Google Scholar
• Rose WC, Lee FY, Fairchild CR et al Preclinical antitumor activity of BMS-214662, a highly apoptotic and novel farnesyltransferase inhibitor. Cancer Res. 61(20), 7507–7517 (2001).
   Google Scholar
• •The FTI BMS-214662 has a distinctive activity that confers cytotoxicity unlike pure FTIs, which are generally considered to be cytostatic.
   Google Scholar
• Ranganathan S, McCauley RA, Hudes GR. 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. Assoc. Cancer Res. 40 (1999) (Abstract 3448).
   Google Scholar
• Sonnichsen D, Damle B, Manning J et al Pharmacokinetics (PK) and pharmacodynamics (PD) of the farnesyltransferase (FT) inhibitor BMS-214662 in patients with advanced solid tumors. Proc. Am. Soc. Clin. Oncol 19 (2000) (Abstract 691).
   Google Scholar
• Shields JM, Pruitt K, McFall A, Shaub A, Der CJ. Understanding Ras: 'it ain't over 'EA it's over'. Trends Cell Biol. 10(4), 147–154 (2000).
   PubMed Web of Science ®Google Scholar
• Cox AD, Der CJ. Farnesyltransferase inhibitors: promises and realities. 6.117: Opin. Pharmacol 2(4), 388–393 (2002).
   Google Scholar
• Cox AD, Der CJ. Farnesyltransferase inhibitors and cancer treatment: targeting simply Ras? Biochem. Biophys. Acta 1333(1), F51—F71 (1997).
   PubMed Web of Science ®Google Scholar
• Prendergast GC, Rane N. Farnesyltransferase inhibitors: mechanism and applications. Expert Opin. Investig. Drugs10(12), 2105–2116 (2001).
   Google Scholar
• Prendergast GC, Du W Targeting farnesyltransferase: is Ras relevant? Drug Resist. Update 2(2), 81–84 (1999).
   Google Scholar
• Du W, Lebowitz PF, Prendergast GC. Cell growth inhibition by farnesyltransferase inhibitors is mediated by gain of geranylgeranylated RhoB. Mal Cell Biol. 19(3), 1831–1840 (1999).
   Web of Science ®Google Scholar
• Liu A, Prendergast GC. Geranylgeranylated RhoB is sufficient to mediate tissue-specific suppression of Akt kinase activity by farnesyltransferase inhibitors. FEBS Lett. 481(3), 205–208 (2000).
   Google Scholar
• •The importance of RhoB proteins is described in relation to FTI responsiveness.
   Google Scholar
• Jiang K, Coppola D, Crespo NC et al The phosphoinositide 3-0H kinase/AKT2 pathway as a critical target for farnesyltransferase inhibitor-induced apoptosis. Mal Cell Biol. 20(1), 139–148 (2000).
   Google Scholar
• Adini I, Rabinovitz I, Sun JF et al. RhoB controls Akt trafficking and stage-specific survival of endothelial cells during vascular development. Genes Dev. 17(21), 2721–2732 (2003).
   Google Scholar
• ••Novel function of RhoB protein, whichinvolves the regulation of endothelial cell survival during vascular development, is described. Also discusses the potential utility of RhoB as a therapeutic target.
   Google Scholar
• Chen Z, Sun J, Pradines A, Favre G, Adnane J, Sebti SM. Both farnesylated and geranylgeranylated RhoB inhibit malignant transformation and suppress human tumor growth in nude mice. j Biol. Chem. 275(24), 17974–17978 (2000).
   Web of Science ®Google Scholar
• ••Landmark study that demonstrated thatin Panc-1 human pancreatic carcinoma cells, both RhoB forms are growth-inhibitory factors, hence arguing the hypothesis of the mechanism of action of FTI involving a shift from RhoB-F to RhoB-GG.
   Google Scholar
• Falugi C, Trombino S, Granone P, Margaritora S, Russo P Increasing complexity of farnesyltransferase inhibitor activity: role in chromosome instability. Corr. Cancer Drug Targets3(2), 109–118 (2003).
   PubMed Web of Science ®Google Scholar
• Crespo NC, Ohkanda J, Yen TJ, Hamilton AD, Sebti SM. The farnesyltransferase inhibitor, F11-2153, blocks bipolar spindle formation and chromosome alignment and causes prometaphase accumulation during mitosis of human lung cancer cells. j Biol. Chem. 276(19), 16161–16167 (2001).
   Google Scholar
• Skorski T, Bellacosa A, Nieborowska-Skorska M et al Transformation of hematopoietic cells by BCIVABL requires activation of a PI3IdAkt dependent pathway. EMI30 16(20), 6151–6161 (1997).
   Google Scholar
• Cowley S, Paterson H, Kemp P, Marshall CJ. Activation of MAPK kinase is necessary and sufficient for PC12 differentiation and for transformation of NIH 3T3 cells. Ce1177(6), 841–852 (1994).
   Google Scholar
• Mansour SJ, Matten WT, Hermann AS et al Transformation of mammalian cells by constitutively active MAPK kinase. Science 265(5174), 966–970 (1994).
   PubMed Web of Science ®Google Scholar
• Bennett AM, Tonics NK. Regulation of distinct stages of skelet al muscle differentiation by mitogen-activated protein kinases. Science 278(5341), 1288–1291 (1997).
   PubMed Web of Science ®Google Scholar
• Whalen AM, Galasinski SC, Shapiro PS, Nahreini TS, Ahn NG. Megakaryocytic differentiation induced by constitutive activation of mitogen-activated protein kinase kinase. Mol Cell Biol. 17(4), 1947–1958 (1997).
   PubMed Web of Science ®Google Scholar
• Raponi M, Belly R, Atkins D et al Pharmacogenomic analysis reveals signaling pathway modulated by R115777 (Zarnestra) in acute myeloid leukemia. Proc. Am. Soc. Clin. Oncol 21,265a (2002) (Abstract 1057).
   Google Scholar
• Schnittger S, Schoch C, Dugas M et al Analysis of FLT3 length mutations in 1003 patients with acute myeloid leukemia: correlation to cytogenetics, FAB subtype, and prognosis in AMLCG study and usefulness as a marker for the detection of minimal residual disease. Blood100(1), 59–66 (2002).
   Google Scholar
• Stirewalt DL, Kopecky KJ, Meshinchi S et al FLT3, RAS, and TP53 mutations in elderly patients with acute myeloid leukemia. B/ooc/97(11), 3589–3595 (2001).
   Google Scholar
• Mizuki M, Fenski R, Halfter H et al F1t3 mutations from patients with acute myeloid leukemia induce transformation of 32D cells mediated by the Ras and STAT5 pathways. B/ooc/96(12), 3907–3914 (2000).
   Google Scholar
• Hayakawa F, Towatari M, Kiyoi H et al Tandem-duplicated Rt3 constitutively activates STAT5 and MAPK and introduces autonomous cell growth in IL-3-dependent cell lines. Oncogene 19(5), 624–631 (2000).
   Google Scholar
• Adjei AA, Erlichman C, Davis JN et al A Phase I trial of the famesyl transferase inhibitor 5CH66336: evidence for biological and clinical activity. Cancer Res. 60(7), 1871–1877 (2000).
   Google Scholar
• Adjei AA, Davis JN, Erlichman C, Svingen PA, Kaufmann SH. Comparison of potential markers of farnesyltransferase inhibition. Clin. Cancer Res. 6(6), 2318–2325 (2000).
   Google Scholar
• •Describes several surrogate markers to determine the FIT dose necessary to inhibit the target farnesyltransferase enzyme.
   Google Scholar
• Adnane J, Bizouarn FA, Chen Z et al Inhibition of farnesyltransferase increases TGF-0 Type II receptor expression and enhances the responsiveness of human cancer cells to TGF-13. Oncogene 19(48), 5525–5533 (2000).
   Google Scholar
• Alcock RA, Dey S, Chendil D et al Famesyltransferase inhibitor (L-744,832) restores TGF-fi Type II receptor expression and enhances radiation sensitivity in K-ras mutant pancreatic cell line MIA PaCa-2. Oncogene 21(51), 7883–7890 (2002).
   Google Scholar
• Medeiros BC, Landau HA, Morrow MC, Eckhardt SG. The farnesyl transferase inhibitor zarnestra (R115777) exhibits a dual mechanism of action against P-glycoprotein overexpressing leukemia cell lines. B/ooc/102, 610a (2003) (Abstract 2250).
   Google Scholar
• Gotlib J, Loh M, Vattikuti S et al Phase I/II study of Zamestra (farnesyltransferase inhibitor [F11] R115777, tipifamib) in patients with myeloproliferative disorders (MPDs): preliminary results. Blood100, 798a (2002) (Abstract 3153).
   Google Scholar
• Cortes J, Albitar M, Thomas D et al. Efficacy of the farnesyl transferase R115777 in chronic myeloid leukemia and other hematologic malignancies. Blood 101 (5), 1692–1697 (2003).
   Google Scholar
• Kurzrock R, Kantarjian HM, Cortes JE et al Farnesyltransferase inhibitor R115777 in myelodysplastic syndrome: clinical and biologic activities in the Phase I setting. B/ooc/102(13), 4527–4534 (2003).
   Google Scholar
• Cortes J, Kurzrock R, O'Brien SM et al. Phase I Study of a farnesyl transferase inhibitor (FTI), BMS-214662, in patients with refractory or relapsed acute leukemias. B/ooc/98, 594a (2001) (Abstract 2489).
   Google Scholar
• List AF, DeAngelo D, O'Brien S et al Phase I study of continuous oral administration of lonafamib (Sarasar) in patients with advanced hematologic malignancies. Blood100, 789a (2002) (Abstract 3120).
   Google Scholar
• Ravoet C, Mineur P, Robin V et al. Phase I—II study of famesyl transferase inhibitor (FTI), 5CH66336, in patients with myelodysplastic syndrome (MDS) or secondary acute myeloid leukemia (sAML). Blood 100, 794a (2002) (Abstract 3136).
   Google Scholar
• Harousseau J-L, Reiffers J, Lowenberg B et al Zamestra (R115777) in patients with relapsed and refractory acute myelogenous leukemia (AML): results of a multicenter Phase II study. B/ooc/102, 176a (2003) (Abstract 614).
   Google Scholar
• Kurzrock R, Albitar M, Cortes JE et al Phase II study of R115777, a famesyl transferase inhibitor, in myelodysplastic syndrome. j Clin. Oncol 22 (7), 1287–1292 (2004).
   Google Scholar
• Lancet JE, Gojo I, Gotlib J et al Tipifamib (Zarnestra) in previously untreated poor-risk AML and MDS: interim results of a Phase II trial. Blood102, 176a (2003) (Abstract 613).
   Google Scholar
• Gotlib J, Loh M, Lancet JE et al. Phase I/II study of tipifarnib (Zarnestra, farnesyltransferase inhibitor [F11] R115777) in patients with myeloproliferative disorders (MPDs): interim results. B/ooc/102, 921a (2003) (Abstract 3425).
   Google Scholar
• Morgan MA, Sebil T, Ganser A, Reuter CWM. Potent inhibition of multiple myeloma cell migration by lovastatin. Blood 102, 443a (2003) (Abstract 1618).
   Google Scholar
• Ochiai N, Yamada N, Uchida R et al Incadronate augments the inhibitory effect of farnesyl transferase inhibitor R115777 (Zarnestra) on the growth of fresh and cloned myeloma cells in vitro. Blood 102, 689a (2003) (Abstract 2552).
   Google Scholar
• Le Gouill S, Pellat-Deceunynck C, Harousseau JL et al Farnesyl transferase inhibitor R115777 induces apoptosis of human myeloma cells. Leukemia 16(9), 1664–1667 (2002).
   Google Scholar
• Alsina M, Fonseca R, Wilson EF et al Famesyltransferase inhibitor tipifarnib is well-tolerated, induces stabilization of disease, and inhibits farnesylation and oncogenic/tumor survival pathways in patients with advanced multiple myeloma. B/ooc/103(9), 3271–3277 (2004).
   Google Scholar
• Cortes J, Holyoake TL, Silver RT et al Continuous oral lonafarnib (Sarasar) for the treatment of patients with advanced hematologic malignancies: a Phase II study. Blood100, 793a (2002) (Abstract 3132).
   Google Scholar
• Feldman EJ, Cortes J, Holyoake TL et al Continuous oral lonafarnib (Sarasar) for the treatment of patients with myelodysplastic syndrome. Blood 102, 421a (2003) (Abstract 1531).
   Google Scholar
• Cortes J, Garcia-Manero G, O'Brien S et al Phase I study of a imatinib and tipifarnib (Zamestra, R115777) in patients with chronic myeloid leukemia in chronic phase refractory to imatinib. Blood 102, 909a (2003) (Abstract 3383).
   Google Scholar
• Gotlib J, Mauro M, O'Dwyer ME et al Tipifarnib (Zarnestra) and imatinib (Gleevec) combination therapy in patients with advanced chronic myelogenous leukemia (CML): preliminary results of a Phase I study. Blood 102, 909a (2003) (Abstract 3384).
   Google Scholar
• Cortes J, O'Brien S, Ferrajoli A et al Phase I study of imatinib and lonafarnib (5CH66336) in patients with chronic myeloid leukemia (CML) refractory to imatinib mesylate. Blood 102, 909a (2003) (Abstract 3382).
   Google Scholar
• Sebti SM, Adjei AA. Famesyltransferase inhibitors. Semin. Oncol 31(1 Suppl. 1), 28–39 (2004).
   Google Scholar