Cancer Treatment Reviews
Volume 27, Issue 6 , Pages 317-326 , December 2001

New molecular targets and biological therapies in sarcomas

  • F.A Scappaticci

      Affiliations

    • Department of Pathology, Stanford University Medical Center, Stanford, CA, USA
  • ,
  • N Marina

      Affiliations

    • Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA

References 

  1. Pisters P WT, Brennan MF. Sarcomas of soft tissue. In:  Abeloff MD,  Armitage JO,  Lichter AS,  Niederhuber JE editor. Clinical Oncology. 2nd Edn. New York: Churchill Livingstone; 2000;p. 2273–2313
  2. Dirix LY, Van Oosterom AT. Soft tissue sarcoma in adults. Curr Opin Oncol. 1999;11:285–295
  3. Eilber F, Giuliano A, Eckardt J, Patterson K, Moseley S, Goodnight J. Adjuvant chemotherapy for osteosarcoma: a randomized prospective trial. J Clin Oncol. 1987;5:21–26
  4. Link MP, Goorin AM, Miser AW, Green AA, Pratt CB, Belasco JB. The effect of adjuvant chemotherapy on relapse-free survival in patients with osteosarcoma of the extremity. N Engl J Med. 1986;314:1600–1606
  5. Rosen G, Caparros B, Nirenberg A, Marcove RC, Huvos AG, Kosloff C. Ewing's sarcoma: ten-year experience with adjuvant chemotherapy. Cancer. 1981;47:2204–2213
  6. Vietti TJ, Gehan EA, Nesbit ME, Burgert EO, Pilepich M, Tefft M. Multimodal therapy in metastatic Ewing's sarcoma: an Intergroup Study. Natl Cancer Inst Monogr. 1981;56:279–284
  7. Thomas PR, Foulkes MA, Gilula LA, Burgert EO, Evans RG, Kissane J. Primary Ewing's sarcoma of the ribs. A report from the intergroup Ewing's sarcoma study. Cancer. 1983;51:1021–1027
  8. Pilepich MV, Vietti TJ, Nesbit ME, Tefft M, Kissane J, Burgert EO. Radiotherapy and combination chemotherapy in advanced Ewing's Sarcoma – Intergroup study. Cancer. 1981;47:1930–1936
  9. Maurer HM, Beltangady M, Gehan EA, Crist W, Hammond D, Hays DM. The Intergroup Rhabdomyosarcoma Study-I. A final report. Cancer. 1988;61:209–220
  10. Elias A, Ryan L, Sulkes A, Collins J, Aisner J, Antman KH. Response to mesna, doxorubicin, ifosfamide, and dacarbazine in 108 patients with metastatic or unresectable sarcoma and no prior chemotherapy. J Clin Oncol. 1989;7:1208–1216
  11. Singer S. New diagnostic modalities in soft tissue sarcoma. Semin Surg Oncol. 1999;17:11–22
  12. Alvegård TA, Berg NO. Histopathology peer review of high-grade soft tissue sarcoma: the Scandinavian Sarcoma Group experience. J Clin Oncol. 1989;7:1845–1851
  13. Turc-Carel C, Aurias A, Mugneret F, Lizard S, Sidaner I, Volk C. Chromosomes in Ewing's sarcoma. I. An evaluation of 85 cases of remarkable consistency of t(11;22)(q24;q12). Cancer Genet Cytogenet. 1988;32:229–238
  14. Douglass EC, Rowe ST, Valentine M, Parham DM, Berkow R, Bowman WP. Variant translocations of chromosome 13 in alveolar rhabdomyosarcoma. Genes Chromosomes Cancer. 1991;3:480–482
  15. Whang-Peng J, Triche TJ, Knutsen T, Miser J, Kao-Shan S, Tsai S. Cytogenetic characterization of selected small round cell tumors of childhood. Cancer Genet Cytogenet. 1986;21:185–208
  16. Whang-Peng J, Knutsen T, Theil K, Horowitz ME, Triche T. Cytogenetic studies in subgroups of rhabdomyosarcoma. Genes Chromosomes Cancer. 1992;5:299–310
  17. Downing JR, Head DR, Parham DM, Douglass EC, Hulshof MG, Link MP. Detection of the (11;22)(q24;q12) translocation of Ewing's sarcoma and peripheral neuroectodermal tumor by reverse transcription polymerase chain reaction. Am J Pathol. 1993;143:1294–1300
  18. Delattre O, Zucman J, Melot T, Garau XS, Zucker JM, Lenoir GM. The Ewing family of tumors – a subgroup of small-round-cell tumors defined by specific chimeric transcripts. N Engl J Med. 1994;331:294–299
  19. de Alava E, Gerald WL. Molecular biology of the Ewing's sarcoma/primitive neuroectodermal tumor family. J Clin Oncol. 2000;18:204–213
  20. Barr FG. Molecular genetics and pathogenesis of rhabdomyosarcoma. J Pediatr Hematol Oncol. 1997;19:483–491
  21. Kelly KM, Womer RB, Sorensen PH, Xiong QB, Barr FG. Common and variant gene fusions predict distinct clinical phenotypes in rhabdomyosarcoma. J Clin Oncol. 1997;15:1831–1836
  22. Ginsberg JP, de Alava E, Ladanyi M, Wexler LH, Kovar H, Paulussen M. EWS-FLI1 and EWS-ERG gene fusions are associated with similar clinical phenotypes in Ewing's sarcoma. J Clin Oncol. 1999;17:1809–1814
  23. Zoubek A, Dockhorn-Dworniczak B, Delattre O, Christiansen H, Niggli F, Gatterer-Menz I. Does expression of different EWS chimeric transcripts define clinically distinct risk groups of Ewing tumor patients?. J Clin Oncol. 1996;14:1245–1251
  24. de Alava E, Kawai A, Healey JH, Fligman I, Meyers PA, Huvos AG. EWS-FLI1 fusion transcript structure is an independent determinant of prognosis in Ewing's sarcoma. J Clin Oncol. 1998;16:1248–1255
  25. Kelly KM, Womer RB, Barr FG. PAX3-FKHR and PAX7-FKHR gene fusions in rhabdomyosarcoma. J Pediatr Hematol Oncol. 1998;20:517–518
  26. Kelly KM, Womer RB, Barr FG. Minimal disease detection in patients with alveolar rhabdomyosarcoma using a reverse transcriptase-polymerase chain reaction method. Cancer. 1996;78:1320–1327
  27. Alizadeh A, Eisen M, Davis RE, Ma C, Sabet H, Tran T. The lymphochip: a specialized cDNA microarray for the genomic-scale analysis of gene expression in normal and malignant lymphocytes. Cold Spring Harb Symp Quant Biol. 1999;64:71–78
  28. Brown PO, Botstein D. Exploring the new world of the genome with DNA microarrays. Nat Genet. 1999;21:33–37
  29. Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA. Molecular portraits of human breast tumours. Nature. 2000;406:747–752
  30. Daley GQ, Van Etten RA, Baltimore D. Induction of chronic myelogenous leukemia in mice by the P210bcr/abl gene of the Philadelphia chromosome. Science. 1990;247:824–830
  31. Kelliher MA, McLaughlin J, Witte ON, Rosenberg N. Induction of a chronic myelogenous leukemia-like syndrome in mice with v-abl and BCR/ABL. Proc Natl Acad Sci USA. 1990;87:6649–6653
  32. Heisterkamp N, Jenster G, ten Hoeve J, Zovich D, Pattengale PK, Groffen J. Acute leukaemia in bcr/abl transgenic mice. Nature. 1990;344:251–253
  33. Lugo TG, Pendergast AM, Muller AJ, Witte ON. Tyrosine kinase activity and transformation potency of bcr-abl oncogene products. Science. 1990;247:1079–1082
  34. Druker BJ, Tamura S, Buchdunger E, Ohno S, Segal GM, Fanning S. Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells. Nat Med. 1996;2:561–566
  35. Deininger MW, Goldman JM, Lydon N, Melo JV. The tyrosine kinase inhibitor CGP57148B selectively inhibits the growth of BCR-ABL-positive cells. Blood. 1997;90:3691–3698
  36. Gambacorti-Passerini C, le Coutre P, Mologni L, Fanelli M, Bertazzoli C, Marchesi E. Inhibition of the ABL kinase activity blocks the proliferation of BCR/ABL+ leukemic cells and induces apoptosis. Blood Cells Mol Dis. 1997;23:380–394
  37. Druker BJ, Talpaz M, Resta DJ, Peng B, Buchdunger E, Ford JM. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med. 2001;344:1031–1037
  38. Druker BJ, Sawyers CL, Kantarjian H, Resta DJ, Reese SF, Ford JM. Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome. N Engl J Med. 2001;344:1038–1042
  39. Sarlomo-Rikala M, Kovatich AJ, Barusevicius A, Miettinen M. CD117: a sensitive marker for gastrointestinal stromal tumors that is more specific than CD34. Mod Pathol. 1998;11:728–734
  40. Hirota S, Isozaki K, Moriyama Y, Hashimoto K, Nishida T, Ishiguro S. Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science. 1998;279:577–580
  41. Lux ML, Rubin BP, Biase TL, Chen CJ, Maclure T, Demetri G. KIT extracellular and kinase domain mutations in gastrointestinal stromal tumors. Am J Pathol. 2000;156:791–795
  42. Joensuu H, Roberts PJ, Sarlomo-Rikala M, Andersson LC, Tervahartiala P, Tuveson D. Effect of the tyrosine kinase inhibitor STI571 in a patient with a metastatic gastrointestinal stromal tumor. N Engl J Med. 2001;344:1052–1056
  43. Tuveson DA, Fletcher JA. Signal transduction pathways in sarcoma as targets for therapeutic intervention. Curr Opin Oncol. 2001;13:249–255
  44. Cox AD, Der CJ. Farnesyltransferase inhibitors and cancer treatment: targeting simply Ras?. Biochim Biophys Acta. 1997;1333:F51–F71
  45. Oliff A. Farnesyltransferase inhibitors: targeting the molecular basis of cancer. Biochim Biophys Acta. 1999;1423:C19–C30
  46. Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med. 1971;285:1182–1186
  47. Hanahan D, Folkman J. Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell. 1996;86:353–364
  48. Bergers G, Javaherian K, Lo KM, Folkman J, Hanahan D. Effects of angiogenesis inhibitors on multistage carcinogenesis in mice. Science. 1999;284:808–812
  49. Folkman J. Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med. 1995;1:27–31
  50. Boehm T, Folkman J, Browder T, O'Reilly MS. Antiangiogenic therapy of experimental cancer does not induce acquired drug resistance. Nature. 1997;390:404–407
  51. Kerbel RS. A cancer therapy resistant to resistance. Nature. 1997;390:335–336
  52. Singhal S, Mehta J, Desikan R, Ayers D, Roberson P, Eddlemon P. Antitumor activity of thalidomide in refractory multiple myeloma. N Engl J Med. 1999;341:1565–1571
  53. Ezekowitz RA, Mulliken JB, Folkman J. Interferon alfa-2a therapy for life-threatening hemangiomas of infancy. N Engl J Med. 1992;326:1456–1463
  54. Jackel A, Deichmann M, Waldmann V, Bock M, Naher H. Regression of metastatic angiosarcoma of the skin after systemic treatment with liposome-encapsulated doxorubicin and interferon-alpha. Br J Dermatol. 1999;140:1187–1188
  55. Spieth K, Gille J, Kaufmann R. Therapeutic efficacy of interferon alfa-2a and 13-cis-retinoic acid in recurrent angiosarcoma of the head. Arch Dermatol. 1999;135:1035–1037
  56. Killeen RB, Marsh RD. Alpha-interferon for Kaposi's sarcoma in HIV-negative, non-homosexual man (letter). Lancet. 1991;337:309–310
  57. Bergsland E, Hurwitz H, Fehrenbacher L, Meropol NJ, Novotny WF, Gaudreault J, et al. A randomized phase II trial comparing rhuMAb VEGF (recombinant humanized monoclonal antibody to vascular endothelial cell growth factor) plus 5-fluorouracil/leucovorin (FU/LV) to FU/LV alone in patients with metastatic colorectal cancer. Proc ASCO. 2000;19:242a
  58. DeVore RF, Fehrenbacher L, Herbst RS, Langer CJ, Kelly K, Gaudreault J, et al. A randomized phase II trial comparing rhumAb VEGF (recombinant humanized monoclonal antibody to vascular endothelial cell growth factor) plus carboplatin/paclitaxel (CP) to CP alone in patients with Stage IIIb/IV NSCLC. Proc ASCO. 2000;19:485a
  59. Folkman J. Antiangiogenic gene therapy. Proc Natl Acad Sci USA. 1998;95:9064–9066
  60. Mendelsohn J, Baselga J. The EGF receptor family as targets for cancer therapy. Oncogene. 2000;19:6550–6565
  61. Shin DM, Donato NJ, Perez-Soler R, Shin HJ, Wu JY, Zhang P. Epidermal growth factor receptor-targeted therapy with C225 and cisplatin in patients with head and neck cancer. Clin Cancer Res. 2001;7:1204–1213
  62. Laird AD, Vajkoczy P, Shawver LK, Thurnher A, Liang C, Mohammadi M. SU6668 is a potent antiangiogenic and antitumor agent that induces regression of established tumors. Cancer Res. 2000;60:4152–4160
  63. Heymach JV. Angiogenesis and antiangiogenic approaches to sarcomas. Curr Opin Oncol. 2001;13:261–269
  64. Stopeck A. Results of a phase I dose-escalating study of the antiangiogenic agent SU5416, in patients with advanced malignancies. Proc ASCO. 2000;19:206a
  65. Patel SR, Jenkins J, Papadopoulos NE, Burgess MA, Plager C, Charnsangavej C, et al. A pilot study of an angiogenesis inhibitor vitaxin in patients with advanced leiomyosarcomas (leios). Proc ASCO. 2000;19:559a
  66. O'Reilly MS, Holmgren L, Shing Y, Chen C, Rosenthal RA, Moses M. Angiostatin: a novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma. Cell. 1994;79:315–328
  67. O'Reilly MS, Boehm T, Shing Y, Fukai N, Vasios G, Lane WS. Endostatin: an endogenous inhibitor of angiogenesis and tumor growth. Cell. 1997;88:277–285
  68. O'Reilly MS, Wiederschain D, Stetler-Stevenson WG, Folkman J, Moses MA. Regulation of angiostatin production by matrix metalloproteinase-2 in a model of concomitant resistance. J Biol Chem. 1999;274:29568–29571
  69. Felbor U, Dreier L, Bryant RA, Ploegh HL, Olsen BR, Mothes W. Secreted cathepsin L generates endostatin from collagen XVIII. EMBO J. 2000;19:1187–1194
  70. Lucas R, Holmgren L, Garcia I, Jimenez B, Mandriota SJ, Borlat F. Multiple forms of angiostatin induce apoptosis in endothelial cells. Blood. 1998;92:4730–4741
  71. Dhanabal M, Ramchandran R, Waterman MJ, Lu H, Knebelmann B, Segal M. Endostatin induces endothelial cell apoptosis. J Biol Chem. 1999;274:11721–11726
  72. Dixelius J, Larsson H, Sasaki T, Holmqvist K, Lu L, Engstrom A. Endostatin-induced tyrosine kinase signaling through the Shb adaptor protein regulates endothelial cell apoptosis. Blood. 2000;95:3403–3411
  73. Kim YM, Jang JW, Lee OH, Yeon J, Choi EY, Kim KW. Endostatin inhibits endothelial and tumor cellular invasion by blocking the activation and catalytic activity of matrix metalloproteinase. Cancer Res. 2000;60:5410–5413
  74. Scappaticci FA, Contreras A, Smith R, Bonhoure L, Lum B, Cao Y, et al. Statin-AE: a novel angiostatin-endostatin fusion protein with enhanced antiangiogenic and antitumor activity. Angiogenesis. 2002;
  75. Scappaticci FA, Smith R, Pathak A, Schloss D, Lum B, Cao Y. Combination angiostatin and endostatin gene transfer induces synergistic antiangiogenic activity in vitro and antitumor efficacy in leukemia and solid tumors in mice. Mol Ther. 2001;3:186–196
  76. Stamenkovic I. Matrix metalloproteinases in tumor invasion and metastasis. Semin Cancer Biol. 2000;10:415–433
  77. Hidalgo M, Eckhardt SG. Development of matrix metalloproteinase inhibitors in cancer therapy. J Natl Cancer Inst. 2001;93:178–193
  78. Kleiner DE, Stetler-Stevenson WG. Matrix metalloproteinases and metastasis. Cancer Chemother Pharmacol. 1999;43:S42–S51
  79. Hua J, Muschel RJ. Inhibition of matrix metalloproteinase 9 expression by a ribozyme blocks metastasis in a rat sarcoma model system. Cancer Res. 1996;56:5279–5284
  80. Mitsiades N, Poulaki V, Leone A, Tsokos M. Fas-mediated apoptosis in Ewing's sarcoma cell lines by metalloproteinase inhibitors. J Natl Cancer Inst. 1999;91:1678–1684
  81. Denis LJ, Verweij J. Matrix metalloproteinase inhibitors: present achievements and future prospects. Invest New Drugs. 1997;15:175–185
  82. Wojtowicz-Praga SM, Dickson RB, Hawkins MJ. Matrix metalloproteinase inhibitors. Invest New Drugs. 1997;15:61–75
  83. Wojtowicz-Praga S, Torri J, Johnson M, Steen V, Marshall J, Ness E. Phase I trial of Marimastat, a novel matrix metalloproteinase inhibitor, administered orally to patients with advanced lung cancer. J Clin Oncol. 1998;16:2150–2156
  84. Brown PD. Matrix metalloproteinase inhibitors. Breast Cancer Res Treat. 1998;52:125–136
  85. Brown PD. Clinical studies with matrix metalloproteinase inhibitors. APMIS. 1999;107:174–180
  86. Shalinsky DR, Brekken J, Zou H, McDermott CD, Forsyth P, Edwards D. Broad antitumor and antiangiogenic activities of AG3340, a potent and selective MMP inhibitor undergoing advanced oncology clinical trials. Ann N Y Acad Sci. 1999;878:236–270
  87. Shalinsky DR, Brekken J, Zou H, Bloom LA, McDermott CD, Zook S. Marked antiangiogenic and antitumor efficacy of AG3340 in chemoresistant human non-small cell lung cancer tumors: single agent and combination chemotherapy studies. Clin Cancer Res. 1999;5:1905–1917
  88. Wilson CL, Heppner KJ, Labosky PA, Hogan BL, Matrisian LM. Intestinal tumorigenesis is suppressed in mice lacking the metalloproteinase matrilysin. Proc Natl Acad Sci USA. 1997;94:1402–1407
  89. Drummond AH, Beckett P, Brown PD, Bone EA, Davidson AH, Galloway WA. Preclinical and clinical studies of MMP inhibitors in cancer. Ann N Y Acad Sci. 1999;878:228–235
  90. Hooper NM, Karran EH, Turner AJ. Membrane protein secretases. Biochem J. 1997;321:265–279
  91. Ferrante K, Winograd B, Canetta R. Promising new developments in cancer chemotherapy. Cancer Chemother Pharmacol. 1999;43:S61–S68
  92. Ries C, Lottspeich F, Dittmann KH, Petrides PE. HL-60 leukemia cells produce an autocatalytically truncated form of matrix metalloproteinase-9 with impaired sensitivity to inhibition by tissue inhibitors of metalloproteinases. Leukemia. 1996;10:1520–1526
  93. Low JJ, Brunner N. Induction of stromal uPA during Batimastat therapy of human breast tumor xenografts. Annual NIH SPORE meeting. 1997;
  94. Hahn H, Wojnowski L, Zimmer AM, Hall J, Miller G, Zimmer A. Rhabdomyosarcomas and radiation hypersensitivity in a mouse model of Gorlin syndrome. Nat Med. 1998;4:619–622
  95. Perez-Losada J, Pintado B, Gutierrez-Adan A, Flores T, Banares-Gonzalez B, del Campo JC. The chimeric FUS/TLS-CHOP fusion protein specifically induces liposarcomas in transgenic mice. Oncogene. 2000;19:2413–2422
  96. Maki RG. Soft tissue sarcoma as a model disease to examine cancer immunotherapy. Curr Opin Oncol. 2001;13:270–274
  97. Mackall C, Berzofsky J, Helman LJ. Targeting tumor specific translocations in sarcomas in pediatric patients for immunotherapy. Clin Orthop. 2000;25–31
  98. Hsu FJ, Caspar CB, Czerwinski D, Kwak LW, Liles TM, Syrengelas A. Tumor-specific idiotype vaccines in the treatment of patients with B-cell lymphoma – long-term results of a clinical trial. Blood. 1997;89:3129–3135
  99. Hsu FJ, Benike C, Fagnoni F, Liles TM, Czerwinski D, Taidi B. Vaccination of patients with B-cell lymphoma using autologous antigen-pulsed dendritic cells. Nat Med. 1996;2:52–58
  100. Dranoff G, Jaffee E, Lazenby A, Golumbek P, Levitsky H, Brose K. Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long-lasting anti-tumor immunity. Proc Natl Acad Sci USA. 1993;90:3539–3543
  101. Gorlick R, Huvos AG, Heller G, Aledo A, Beardsley GP, Healey JH. Expression of HER2/erbB-2 correlates with survival in osteosarcoma. J Clin Oncol. 1999;17:2781–2788
  102. Ewer MS, Gibbs HR, Swafford J, Benjamin RS. Cardiotoxicity in patients receiving transtuzumab (Herceptin): primary toxicity, synergistic or sequential stress, or surveillance artifact?. Semin Oncol. 1999;26:96–101
  103. Dias S, Hattori K, Zhu Z, Heissig B, Choy M, Lane W. Autocrine stimulation of VEGFR-2 activates human leukemic cell growth and migration. J Clin Invest. 2000;106:511–521
  104. Patel SR, Benjamin RS. New chemotherapeutic strategies for soft tissue sarcomas. Semin Surg Oncol. 1999;17:47–51
  105. Demetri GD, Spiegelman B, Fletcher CD, Mueller E, Sarraf P, Naujoks R, et al. Differentiation of liposarcomas in patients treated with the PPAR ligand troglitazone: documentation of biologic activity in myxoid/round cell and pleomorphic subtypes. Proc ASCO. 1999;18:535a
  106. Demetri GD, Fletcher CD, Mueller E, Sarraf P, Naujoks R, Campbell N. Induction of solid tumor differentiation by the peroxisome proliferator-activated receptor-gamma ligand troglitazone in patients with liposarcoma. Proc Natl Acad Sci USA. 1999;96:3951–3956
  107. Naldini L, Verma IM. Lentiviral vectors. Adv Virus Res. 2000;55:599–609
  108. Qian HS, Channon K, Neplioueva V, Wang Q, Finer M, Tsui L. Improved adenoviral vector for vascular gene therapy: beneficial effects on vascular function and inflammation. Circ Res. 2001;88:911–917
  109. Dubensky TW, Liu MA, Ulmer JB. Delivery systems for gene-based vaccines. Mol Med. 2000;6:723–732
  110. Stephan DJ, Yang ZY, San H, Simari RD, Wheeler CJ, Felgner PL. A new cationic liposome DNA complex enhances the efficiency of arterial gene transfer in vivo. Hum Gene Ther. 1996;7:1803–1812
  111. Milas M, Yu D, Lang A, Ge T, Feig B, El-Naggar AK. Adenovirus-mediated p53 gene therapy inhibits human sarcoma tumorigenicity. Cancer Gene Ther. 2000;7:422–429
  112. Catzavelos C, Bhattacharya N, Ung YC, Wilson JA, Roncari L, Sandhu C. Decreased levels of the cell-cycle inhibitor p27Kip1 protein: prognostic implications in primary breast cancer. Nat Med. 1997;3:227–230
  113. Loda M, Cukor B, Tam SW, Lavin P, Fiorentino M, Draetta GF. Increased proteasome-dependent degradation of the cyclin-dependent kinase inhibitor p27 in aggressive colorectal carcinomas. Nat Med. 1997;3:231–234
  114. Oliveira AM, Nascimento AG, Okuno SH, Lloyd RV. p27(kip1) protein expression correlates with survival in myxoid and round-cell liposarcoma. J Clin Oncol. 2000;18:2888–2893
  115. Meye A, Wurl P, Bache M, Bartel F, Grunbaum U, Mansa-ard J. Colony formation of soft tissue sarcoma cells is inhibited by lipid-mediated antisense oligodeoxynucleotides targeting the human mdm2 oncogene. Cancer Lett. 2000;149:181–188
  116. Korn EL, Arbuck SG, Pluda JM, Simon R, Kaplan RS, Christian MC. Clinical trial designs for cytostatic agents: are new approaches needed?. J Clin Oncol. 2001;19:265–272
  117. Poon RT, Fan ST, Wong J. Clinical implications of circulating angiogenic factors in cancer patients. J Clin Oncol. 2001;19:1207–1225
  118. Oda T, Heaney C, Hagopian JR, Okuda K, Griffin JD, Druker BJ. Crkl is the major tyrosine-phosphorylated protein in neutrophils from patients with chronic myelogenous leukemia. J Biol Chem. 1994;269:22925–22928
  119. Nichols GL, Raines MA, Vera JC, Lacomis L, Tempst P, Golde DW. Identification of CRKL as the constitutively phosphorylated 39-kD tyrosine phosphoprotein in chronic myelogenous leukemia cells. Blood. 1994;84:2912–2918
  120. ten Hoeve J, Arlinghaus RB, Guo JQ, Heisterkamp N, Groffen J. Tyrosine phosphorylation of CRKL in Philadelphia+ leukemia. Blood. 1994;84:1731–1736
  121. Heaney C, Kolibaba K, Bhat A, Oda T, Ohno S, Fanning S. Direct binding of CRKL to BCR-ABL is not required for BCR-ABL transformation. Blood. 1997;89:297–306

PII: S0305-7372(01)90242-7

doi: 10.1053/ctrv.2001.0242

Cancer Treatment Reviews
Volume 27, Issue 6 , Pages 317-326 , December 2001