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Targeted therapies in the treatment of pancreatic carcinoma

Tratamientos dirigidos contra dianas moleculares en cáncer de páncreas

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Abstract

Pancreatic carcinoma is the fifth leading cause of cancer deaths in the western world. Although some progress has been made in the clinical management of pancreatic cancer, surgical resection remains the only potentially curative treatment. New strategies are urgently needed for the treatment of this disease. Advances in knowledge in genetics and molecular biology have led to the development of novel treatments targeting specific molecules. Todate, the results obtained with these new drugs have not been superior to those observed with conventional chemotherapy. In the present article we review some of the new therapies for pancreatic cancer such as the use of inhibitors of epidermal growth factor receptors, the inhibitors of metalloproteases of the extracellular matrix, the inhibitors of farnesyltransferase, and the use of anti-angiogenic treatment.

Resumen

El cáncer de páncreas es la quinta causa de muerte por cáncer en los países desarrollados. A pesar de ciertos avances en el tratamiento médico de esta enfermedad, la resección quirúrgica continúa siendo la única opción curativa. Se necesitan urgentemente nuevas estrategias en el tratamiento del cáncer de páncreas. Los avances en el conocimiento sobre genética y biología molecular han dado lugar al desarrollo de nuevos tratamientos dirigidos contra dianas moleculares específicas. Hasta el momento, los resultados obtenidos con el uso de estos nuevos fármacos no han sido superiores a los observados con el uso de quimioterapia convencional. En este artículo revisaremos algunos de estos nuevos tratamientos, en concreto el uso de inhibidores del receptor del factor de crecimiento epidérmico, los inhibidores de las metaloproteasas de la matriz extracelular, los inhibidores de farnesiltransferasa, y el empleo de tratamientos antiangiogénicos en el cáncer de páncreas.

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References

  1. Niederhuber JE, Brennan MF, Menck HR. The National Cancer Data Base report on pancreatic cancer. Cancer 1995;76(9):1671–7.

    Article  CAS  PubMed  Google Scholar 

  2. Warshaw AL, Fernandez-del Castillo C. Pancreatic carcinoma. N Engl J Med 1992;326(7):455–65.

    Article  CAS  PubMed  Google Scholar 

  3. Kern S, Hruban R, Hollingsworth MA, et al. A white paper: the product of a pancreas cancer think tank. Cancer Res 2001;61(12):4923–32.

    CAS  PubMed  Google Scholar 

  4. Ahrendt SA, Pitt HA. Surgical management of pancreatic cancer. Oncology (Huntingt) 2002;16(6):725–34: discussion 34. 36–8, 40, 43.

    Google Scholar 

  5. Hruban RH, Wilentz RE, Goggins M, Offerhaus GJ, Yeo CJ, Kern SE. Pathology of incipient pancreatic cancer. Ann Oncol 1999;10(Suppl 4):9–11.

    Article  PubMed  Google Scholar 

  6. Bardeesy N, DePinho RA. Pancreatic cancer biology and genetics. Nat Rev Cancer 2002;2(12):897–909.

    Article  CAS  PubMed  Google Scholar 

  7. Ullrich A, Schlessinger J. Signal transduction by receptors with tyrosine kinase activity. Cell 1990;61(2):203–12.

    Article  CAS  PubMed  Google Scholar 

  8. Olayioye MA, Neve RM, Lane HA, Hynes NE. The ErbB signaling network: receptor heterodimerization in development and cancer. EMBO J 2000;19(13):3159–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Woodburn JR. The epidermal growth factor receptor and its inhibition in cancer therapy. Pharmacol Ther 1999;82(2–3):241–50.

    Article  CAS  PubMed  Google Scholar 

  10. Lacroix H, Iglehart JD, Skinner MA, Kraus MH. Overexpression of erbB-2 or EGF receptor proteins present in early stage mammary carcinoma is detected simultaneously in matched primary tumors and regional metastases. Oncogene 1989;4(2):145–51.

    CAS  PubMed  Google Scholar 

  11. Klijn JG, Berns PM, Schmitz PI, Foekens JA. The clinical significance of epidermal growth factor receptor (EGFR) in human breast cancer: a review on 5232 patients. Endocr Rev 1992;13(1):3–17.

    CAS  PubMed  Google Scholar 

  12. Veale D, Kerr N, Gibson GJ, Kelly PJ, Harris AL. The relationship of quantitative epidermal growth factor receptor expression in non-small cell lung cancer to long term survival. Br J Cancer 1993;68(1):162–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Volm M, Rittgen W, Drings P. Prognostic value of ERBB-1, VEGF, cyclin A, FOS, JUN and MYC in patients with squamous cell lung carcinomas. Br J Cancer 1998;77(4): 663–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Ohsaki Y, Tanno S, Fujita Y, et al. Epidermal growth factor receptor expression correlates with poor prognosis in non-small cell lung cancer patients with p53 overexpression. Oncol Rep 2000;7(3):603–7.

    CAS  PubMed  Google Scholar 

  15. Fischer-Colbrie J, Witt A, Heinzl H, et al. EGFR and steroid receptors in ovarian carcinoma: comparison with prognostic parameters and outcome of patients. Anticancer Res 1997;17(1B):613–9.

    CAS  PubMed  Google Scholar 

  16. Ang KK, Berkey BA, Tu X, et al. Impact of epidermal growth factor receptor expression on survival and pattern of relapse in patients with advanced head and neck carcinoma. Cancer Res 2002;62(24):7350–6.

    CAS  PubMed  Google Scholar 

  17. Lemoine NR, Hughes CM, Barton CM, et al. The epidermal growth factor receptor in human pancreatic cancer. J Pathol 1992;166(1):7–12.

    Article  CAS  PubMed  Google Scholar 

  18. Yamanaka Y, Friess H, Kobrin MS, Buchler M, Beger HG, Korc M. Coexpression of epidermal growth factor receptor and ligands in human pancreatic cancer is associated with enhanced tumor aggressiveness. Anticancer Res 1993;13(3):565–9.

    CAS  PubMed  Google Scholar 

  19. Perrotte P, Matsumoto T, Inoue K, et al. Anti-epidermal growth factor receptor antibody C225 inhibits angiogenesis in human transitional cell carcinoma growing orthotopically in nude mice. Clin Cancer Res 1999;5(2): 257–65.

    CAS  PubMed  Google Scholar 

  20. Baselga J. The EGFR as a target for anticancer therapy-focus on cetuximab. Eur J Cancer 2001;37 (Suppl 4):S16–22.

    Article  Google Scholar 

  21. Gill GN, Kawamoto T, Cochet C, et al. Monoclonal anti-epidermal growth factor receptor antibodies which are inhibitors of epidermal growth factor binding and antagonists of epidermal growth factor binding and antagonists of epidermal growth factor-stimulated tyrosine protein kinase activity. J Biol Chem 1984;259(12):7755–60.

    CAS  PubMed  Google Scholar 

  22. Sato JD, Kawamoto T, Le AD, Mendelsohn J, Polikoff J, Sato GH. Biological effectsin vitro of monoclonal antibodies to human epidermal growth factor receptors. Mol Biol Med 1983;1(5):511–29.

    CAS  PubMed  Google Scholar 

  23. Liu B, Fang M, Schmidt M, Lu Y, Mendelsohn J, Fan Z. Induction of apoptosis and activation of the caspase cascade by anti-EGF receptor monoclonal antibodies in Di-Fi human colon cancer cells do not involve the c-jun N-terminal kinase activity. Br J Cancer 2000;82(12):1991–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Ciardiello F, Bianco R, Damiano V, et al. Antiangiogenic and antitumor activity of anti-epidermal growth factor receptor C225 monoclonal antibody in combination with vascular endothelial growth factor antisense oligonucleotide in human GEO colon cancer cells. Clin Cancer Res 2000;6(9):3739–47.

    CAS  PubMed  Google Scholar 

  25. Overholser JP, Prewett MC, Hooper AT, Waksal HW, Hicklin DJ. Epidermal growth factor receptor blockade by antibody IMC-C225 inhibits growth of a human pancreatic carcinoma xenograft in nude mice. Cancer 2000;89(1):74–82.

    Article  CAS  PubMed  Google Scholar 

  26. Goldstein NI, Prewett M, Zuklys K, Rockwell P, Mendelsohn J. Biological efficacy of a chimeric antibody to the epidermal growth factor receptor in a human tumor xenograft model. Clin Cancer Res 1995;1(11):1311–8.

    CAS  PubMed  Google Scholar 

  27. Bruns CJ, Harbison MT, Davis DW, et al. Epidermal growth factor receptor blockade with C225 plus gemcitabine results in regression of human pancreatic carcinoma growing orthotopically in nude mice by antiangiogenic mechanisms. Clin Cancer Res 2000;6(5):1936–48.

    CAS  PubMed  Google Scholar 

  28. Karashima T, Sweeney P, Slaton JW, et al. Inhibition of angiogenesis by the antiepidermal growth factor receptor antibody ImClone C225 in androgen-independent prostate cancer growing orthotopically in nude mice. Clin Cancer Res 2000;8(5):1253–64.

    Google Scholar 

  29. Prewett M, Hooper A, Bassi R, et al. Enhanced tumor activity of anti-epidermal growth factor receptor monoclonal antibody cetuximab (IMC-C225) in combination with irinotecan (CPT-11), 5-FU, and leucovorin against human colorectal carcinoma xenografts. 14 th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics 2002.

  30. Huang SM, Harari PM. Modulation of radiation response after epidermal growth factor receptor blockade in squamous cell carcinomas: inhibition of damage repair, cell cycle kinetics, and tumor angiogenesis. Clin Cancer Res 2000;6(6):2166–74.

    CAS  PubMed  Google Scholar 

  31. Harari PM, Huang SM. Radiation response modification following molecular inhibition of epidermal growth factor receptor signaling. Semin Radiat Oncol 2001;11(4):281–9.

    Article  CAS  PubMed  Google Scholar 

  32. Harari PM, Huang SM. Epidermal growth factor receptor modulation of radiation response: preclinical and clinical development. Semin Radiat Oncol 2002;12(3 Suppl 2): 21–6.

    Article  PubMed  Google Scholar 

  33. Bianco C, Bianco R, Tortora G, et al. Antitumor activity of combined treatment of human cancer cells with ionizing radiation and anti-epidermal growth factor receptor monoclonal antibody C225 plus type I protein kinase A antisense oligonucleotide. Clin Cancer Res 2000;6(11): 4343–50.

    CAS  PubMed  Google Scholar 

  34. Ciardiello F, Tortora G. Interactions between the epidermal growth factor receptor and type I protein kinase A: biological significance and therapeutic implications. Clin Cancer Res 1998;4(4):821–8.

    CAS  PubMed  Google Scholar 

  35. Ye D, Mendelsohn J, Fan Z. Augmentation of a humanized anti-HER2 mAb 4D5 induced growth inhibition by a human-mouse chimeric anti-EGF receptor mAb C225. Oncogene 1999;18(3):731–8.

    Article  CAS  PubMed  Google Scholar 

  36. Shin DM, Donato NJ, Pérez-Soler R, et al. Epidermal growth factor receptor-targeted therapy with C225 and cisplatin in patients with head and neck cancer. Clin Cancer Res 2001;7(5):1204–13.

    CAS  PubMed  Google Scholar 

  37. Baselga J, Pfister D, Cooper MR, et al. Phase I studies of anti-epidermal growth factor receptor chimeric antibody C225 alone and in combination with cisplatin. J Clin Oncol 2000;18(4):904–14.

    CAS  PubMed  Google Scholar 

  38. Abbruzzese JRA, Rosemberg A, Xiong Q, et al. Phase II study of anti-epidermal growth factor receptor (EGFR) antibody cetuximab (IMC-225) in combination with gemcitabine in patients with advanced pancreatic cancer. American Society of Clinical Oncology Annual Meeting 2001;20:130a.

    Google Scholar 

  39. Burris HA, 3rd, Moore MJ, Andersen J, et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol 1997;15(6):2403–13.

    CAS  PubMed  Google Scholar 

  40. Tabernero JRF, Rojo F, Jiménez E, et al. A phase I pharmacokinetic (PK) and serial tumor and skin pharmacodynamic (PD) study of weekly, every 2 weeks or every 3 weeks 1-hour (h) infusion EMD72000, an humanized monoclonal anti-epidermal growth factor receptor (EGFR) antibody, in patients with solid tumors. 14th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapentics 2002;38:69.

    Google Scholar 

  41. Yang XD, Jia XC, Corvalan JR, et al. Development of ABX-EGF, a fully human an anti-EGF receptor monoclonal antibody, for cancer therapy. Crit Rev Oncol Hematol 2001;38(1):17–23.

    Article  CAS  PubMed  Google Scholar 

  42. Crombet-Ramos T, Rak J, Pérez R, Viloria-Petit A. Antiproliferative, antiangiogenic and proapoptotic activity of h-R3: A humanized anti-EGFR antibody. Int J Cancer 2002;101(6):567–75.

    Article  CAS  PubMed  Google Scholar 

  43. Pérez-Soler R. Chachoua A. Huberman M. et al A phase II trial fo the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor OSI-774, following platinun-based chemotherapy in patients with advanced, EGFR-expressing, non-small cell lung cancer (NSCLC). American Society of Clinical Oncology, Annual Meeting 2000; 20.

  44. Senzer NN, Sonlieres D, Sin L, et al. Phase II evaluation of OSI-774, a potent oral antagonist of the EGFR-TK in patients with advanced squamous cell carcinoma of the head and neck. American Society of Clinical Oncology, Annal Meeting 2001:20:2a.

    Google Scholar 

  45. Fukuoka M, Yano S, Giaccone G, et al. Final results from a phase II trial of ZD1839 (‘Iressa’) for patients with advanced non-small-cell lung cancer (IDEAL 1) American Society of Clinical Oncology, Annual Meeting 2002; 21.

  46. Finkler N, Gordon A. Crozier M, et al. Phase II evaluation of OSI-774, a potent oral antagonist of the EGFR-TK in patients with advanced ovarian carcinoma American Society of Clinical Oncology Annual Meeting 2001.

  47. Cohen EW, Rosen F, Dekker A, et al. Phase II study of ZD1839 (Tressa) in recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN). American Society of Clinical Oncology, Annual Meeting 2002; 21:225a.

    Google Scholar 

  48. Drucker BJ, Shwartz L, Marion S, et al. Phase II trial of ZD1839 (Iressa), an EGF inhibitor, in patients with advanced renal cell carcinoma. American Society of Clinical Oncology 2002;21:Abstr. 720.

    Google Scholar 

  49. Chambers AF, Matrisian LM. Changing views of the role of matrix metalloproteinases in metastesis. J Natl Cancer Inst 1997;89(17):1260–70.

    Article  CAS  PubMed  Google Scholar 

  50. Zucker S, Cao J, Chen WT. Citical appraisal of the use of matrix metalloproteinase inhibitors in cancer treatment. Oncogene 2000;19(56):6642–50.

    Article  CAS  PubMed  Google Scholar 

  51. Lee CS, Montebello J, Georgiou T, Rode J. Distribution of type IV collagen in pancreatic adenocarcinoma and chronic pancreatitis. Int J Exp Pathol 1994;75(2):79–83.

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Wang ZH, Manabe T, Ohshio G, et al. Immunohistochemical study of heparan sulfate proteoglycan in adenocarcinomas of the pancreas. Pancreas 1994;9(6):758–63.

    Article  CAS  PubMed  Google Scholar 

  53. Hidalgo M, Eckhardt SG. Development of matrix metalloproteinase inhibitors in cancer therapy. J Natl Cancer Inst 2001;93(3):178–93.

    Article  CAS  PubMed  Google Scholar 

  54. Ponton A, Coulombe B, Skup D. Decreased expression of tissue inhibitor of metalloproteinases in metastatic tumor cells leading to increased levels of collagenase activity. Cancer Res 1991;51(8):2138–43.

    CAS  PubMed  Google Scholar 

  55. Yamamoto H, Itoh F, Iku S, et al. Expression of matrix metaloproteinases and tissue inhibitors of metalloproteinases in human pancreatic adenocarcinomas: clinicopathologic and prognostic significance of matrilysin expression. J Clin Oncol 2001;19(4):1118–27.

    CAS  PubMed  Google Scholar 

  56. Betz M, Huxley P, Davies SJ, et al. 1.8-A crystal structure of the catalytic domain of human neutrophil collagenase (matrix metalloproteinase-8) complexed with a peptidomimetic hydroxamate primed-side inhibitor with a distinct selectivity profile. Eur J Biochem 1997;247(1):356–63.

    Article  CAS  PubMed  Google Scholar 

  57. Wojtowicz-Praga S, Low J, Marshall J, et al. Phase I trial of a novel matrix metalloproteinase inhibitor batimastat (BB-94) in patients with advanced cancer. Invest New Drugs 1996;14(2):193–202.

    Google Scholar 

  58. Macaulay VM, O'Byrne KJ, Saunders MP, et al. Phase I study of intrapleural batimastat (BB-94), a matrix metalloproteinase inhibitor, in the treatment of malignant pleural effusions. Clin Cancer Res 1999;5(3):513–20.

    CAS  PubMed  Google Scholar 

  59. Beattie GJ, Smyth JF. Phase I study of intraperitoneal metalloproteinase inhibitor BB94 in patients with malignant ascites. Clin Cancer Res 1998;4(8):1899–902.

    CAS  PubMed  Google Scholar 

  60. Millar AW, Brown PD, Moore J, et al. Results of single and repeat dose studies of the oral matrix metalloproteinase inhibitor marimastat in healthy male volunteers. Br J Clin Pharmacol 1998;45(1):21–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Wojtowicz-Praga S, Torri J, Johnson M, et al. Phase I trial of Marimastat, a novel matrix metalloproteinase inlibitor, administered orally to patients with advanced lung cancer. J Clin Oncol 1998;16(6):2150–6.

    CAS  PubMed  Google Scholar 

  62. Primrose JN, Bleiberg H, Daniel F, et al. Marimastat in recurrent colorectal cancer: exploratory evaluation of biological activity by measurement of carcinoembryonic antigen. Br J Cancer 1999;79(3–4):509–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Rosemurgy A, Harris J, Langleben A, Casper E, Goode S, Rasmussen H. Marimastat in patients with advanced pancreatic cancer: a dose-finding study. Am J Clin Oncol 1999;22(3):247–52.

    Article  CAS  PubMed  Google Scholar 

  64. Bourthe A, Eisenhaver E, Steward W, et al. Phase I–II study of marimastat (BB2516) in patients (pts) with metastatic melanoma. American Society of Clinical Oncology 1997; 16.

  65. Carmichael J, Lederman, J, Woll PG, et al. Phase IB study of concurrent administration of marimastat and gemcitabine in non-resectable pancreatic cancer. American Society of Clinical Oncology 1998; 17.

  66. O'Reilly S, Mani S, Ratain M, et al.: Schedules of 5-FU and the matrix metalloproteinase inhibitor marimastat (MAR); a phase I study. American Society of Clinical Oncology 1998; 17.

  67. Adams M TH. A phase I study of the matrix metalloproteinase inhibitor marimastat, administered concurrently with carboplatin, to patients with relapse ovarian cancer. American Society of Clinical Oncology 1998; 17.

  68. Anderson I, Supko J, Eder J, et al. Pilot pharmacokinetic study of marimastat (MAR) in combination with carboplatin (C)/paclitaxel (T) in patients with metastatic or locally advanced inoperable non-small cell lung cancer (NSCLC) American Society of Clinical Oncology 1999; 18.

  69. Nemunaitis J, Poole C, Primrose J, et al. Combined analysis of studies of the effects of the matrix metalloproteinase inhibitor marimastat on serum tumor markers in advanced cancer: selection of a biologically active and tolerable dose for longer-term studies. Clin Cancer Res 1998;4(5):1101–9.

    CAS  PubMed  Google Scholar 

  70. Evans JD, Stark A, Johnson CD, et al. A phase II trial of marimastat in advanced pancreatic cancer. Br J Cancer 2001;85(12):1865–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Bramhall SR, Rosemurgy A, Brown PD, Bowry C, Buckels JA. Marimastat as first-line therapy for patients with unresectable pancreatic cancer: a randomized trial. J Clin Oncol 2001;19(15):3447–55.

    CAS  PubMed  Google Scholar 

  72. Bramhall SR, Schulz J, Nemunaitis J, Brown PD, Baillet M, Buckels JA. A double-blind placebo-controlled, randomised study comparing gemcitabine and marimastat with gem citabine and placebo as first line therapy in patients with advanced pancreatic cancer. Br J Cancer 2002;87(2):161–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Brown PD. Clinical studies with matrix metallproteinase inhibitors. Apmis 1999;107(1):174–80.

    Article  CAS  PubMed  Google Scholar 

  74. Moore MJ, Hamm P, Eisenberg P, et al. A comparison between gemcitabine (GEM) and the matrix metalloproteinase (MMP) inhibitor BAY 12-9566 (9566) in patients (pts) with advanced pancreatic cancer. American Society of Clinical Oncology. Annual Meeting 2000;19:240a.

    Google Scholar 

  75. Downward J. Targeting RAS signalling pathways in cancer therapy. Nat Rev Cancer 2003;3(1):11–22.

    Article  CAS  PubMed  Google Scholar 

  76. Adjei AA. Farnesyltransferase inhibitors. Cancer Chemother Biol Response Modif 2001;19:149–64.

    CAS  PubMed  Google Scholar 

  77. 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 Natl Acad Sci USA 1992;89(14):6403–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Rowinsky EK, Windle JJ, Von Hoff DD. Ras protein farnesyltransferase: A strategic target for anticancer therapentic development. J Clin Oncol 1999;17(11):3631–52.

    CAS  PubMed  Google Scholar 

  79. Lebowitz PF, Prendergast GC. Non-Ras targets of farnesyltransferase inhibitors: focus on Rho. Oncogene 1998;17(11 Reviews):1439–45.

    Article  CAS  PubMed  Google Scholar 

  80. Todd AV, Applegate TL, Fuery CJ, et al. Farnesyl transferase inhibitor (FTI): effect on Ras activation. American Association for Cancer Research, Annual Meeting 1998;39:2168.

    Google Scholar 

  81. 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):927–41.

    CAS  PubMed  Google Scholar 

  82. Nakagawa K, Yamamoto N, Nishio K, et al. A phase I, pharmacokinetic (pk) and pharmacodynamic (pd) study of the farnesyltranfesase inhibitor (FTI) R115777 in Japanese patients with advanced non-hematological malignancies. American Society of Clinical Oncology, Annual Meeting 2001;20:317.

    Google Scholar 

  83. Punt CJ, van Maanen L, Bol CJ, Seifert WF, Wagener DJ. Phase I and pharmacokinetic study of the orally administered farnesyl transferase inhibitor R115777 in patients with advanced solid tumors. Anticancer Drugs 2001;12(3):193–7.

    Article  CAS  PubMed  Google Scholar 

  84. Schellens J, de Klerk G, Swart M, et al. Phase I and pharmacologic study with the novel farnesyl transferase inhibitor (FTI) R115777. American Society of Clinical Oncology 2000;19:715.

    Google Scholar 

  85. Cohen SJ, Ho L, Ranganathan S, et al. Phase II and pharmacodynamic study of the farnesyltransferase inhibitor R115777 as initial therapy in patients with metastatic pancreatic adenocarcinoma. J Clin Oncol 2003;21(7):1301–6.

    Article  CAS  PubMed  Google Scholar 

  86. McDonald J, Chansky K, Whitehead R, et al. A phase II study of farnesyl transferase inhibitor R115777 in pancreatic carcinoma. A Southwest Oncology Group study. American Society of Clinical Oncology 2002;21:545.

    Google Scholar 

  87. Van Cutsem E, Karasek P, Oettle H, et al. Phase III trial comparing gemcitabine + R115777 (Zarnestra) versus gemcitabine+ placebo in advanced pancreatic cancer. American Society of Clinical Oncology. Annual Meeting 2002;21:517.

    Google Scholar 

  88. Bishop WR, Bond R, Petrin J, et al. Novel tricyclic inhibitors of farnesyl protein transferase. Biochemical characterization and inhibition of Ras modification in transfected Cos cells. J Biol Chem 1995;270(51):30611–8.

    Article  CAS  PubMed  Google Scholar 

  89. 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):4947–56.

    CAS  PubMed  Google Scholar 

  90. 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):1167–75.

    CAS  PubMed  Google Scholar 

  91. Kies MS, Clayman GL, El-Naggar AK, et al. Induction therapy with SCH66336, a farnesyltranferase inhibitor, in squamous cell carcinoma (SCC) of the head and neck. American Society of Clinical Oncology, Annual Meeting 2001; 20:896.

    Google Scholar 

  92. Adjei AA, Erlichman C, Davis JN, et al. A Phase I trial of the farnesyl transferase inhibitor SCH66336; evidence for biological and clinical activity. Cancer Res 2000; 60(7):1871–7.

    CAS  PubMed  Google Scholar 

  93. Lersch C, Van Cutsem E, Amado R. et al. Randomized phase II study of SCH66336 and gemcitabine in the treatment of metastatic adenocarcinoma of the pancreas. American Society of Clinical Oncology, Annual Meeting 2001;20:608.

    Google Scholar 

  94. Scappaticci FA. Mechanisms and future directions for angiogenesis-based cancer therapies. J Clin Oncol 2002;20(18):3906–27.

    Article  CAS  PubMed  Google Scholar 

  95. Knoll MR, Rudnitzki D, Sturm J, Manegold BC, Post S, Jaeger TM. Correlation of postoperative survival and angiogenic growth factors in pancreatic carcinoma. Hepatogastroenterology 2001;48(40):1162–5.

    CAS  PubMed  Google Scholar 

  96. Ikeda N, Adachi M, Taki T, et al. Prognostic significance of angiogenesis in human pancreatic cancer. Br J Cancer 1999;79(9–10):1553–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Fujioka S, Yoshida K, Yanagisawa S, Kawakami M, Aoki T, Yamazaki Y. Angiogenesis in pancreatic carcinoma: thymidine phosphorylase expression in stromal cells and intratumoral microvessel density as independent predictors of overall and relapse-free survival. Cancer 2001;92(7):1788–97.

    Article  CAS  PubMed  Google Scholar 

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  1. The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Johns Hopkins University School of Medicine, The Baunting and Blaustein Cancer Research Building, 1650 Orleans St. Room 1M88, 21231, Baltimore, MD, USA

    María Luz Amador Muñoz & Manuel Hidalgo Medina

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  1. María Luz Amador Muñoz
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Correspondence to Manuel Hidalgo Medina.

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MLA is supported by grant 01/9563 from the Instituto de Salud Carlos III, Madrid, Spain.

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Muñoz, M.L.A., Medina, M.H. Targeted therapies in the treatment of pancreatic carcinoma. Rev Oncol 5, 434–442 (2003). https://doi.org/10.1007/BF02710366

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