Glivec (ST1571, imatinib), a rationally developed, targeted anticancer drug

Nature Reviews Drug Discovery

Volumn 1, Issue 7, 2002, Pages 493-502

  Capdeville, Renaud ^a   Buchdunger, Elisabeth ^a   Zimmermann, Juerg ^a   Matter, Alex ^a  

^a NOVARTIS PHARMA AG   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

ANTILEUKEMIC AGENT; ANTINEOPLASTIC AGENT; BCR ABL PROTEIN; CYTARABINE; IMATINIB; INTERFERON; MITOGEN ACTIVATED PROTEIN KINASE; PEGINTERFERON ALPHA2A; PLATELET DERIVED GROWTH FACTOR; PLATELET DERIVED GROWTH FACTOR ALPHA RECEPTOR; PLATELET DERIVED GROWTH FACTOR BETA RECEPTOR; PROTEIN KINASE C; PROTEIN TYROSINE KINASE; PROTON TRANSPORTING ADENOSINE TRIPHOSPHATE SYNTHASE; STEM CELL FACTOR; VASCULOTROPIN; BCR ABL TYROSINE KINASE; BCR-ABL TYROSINE KINASE; ENZYME INHIBITOR; PIPERAZINE DERIVATIVE; PLATELET DERIVED GROWTH FACTOR RECEPTOR; PYRIMIDINE DERIVATIVE; STEM CELL FACTOR RECEPTOR;

CANCER RESEARCH; CHROMOSOME 22; CHROMOSOME 9; CHROMOSOME TRANSLOCATION; CHRONIC MYELOID LEUKEMIA; CLINICAL TRIAL; DISEASE COURSE; DOSE RESPONSE; DRUG BIOAVAILABILITY; DRUG RESEARCH; DRUG RESPONSE; DRUG TARGETING; EDEMA; ENZYME ACTIVATION; ENZYME INHIBITION; ENZYME PHOSPHORYLATION; FLUID RETENTION; GASTROINTESTINAL STROMAL TUMOR; HUMAN; LIVER TOXICITY; MOUSE; MUSCLE CRAMP; NAUSEA; NEUTROPENIA; NONHUMAN; PHILADELPHIA 1 CHROMOSOME; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION; THROMBOCYTOPENIA; VOMITING; ANIMAL; CHEMISTRY; DRUG ANTAGONISM; DRUG EFFECT;

ANIMALS; ANTINEOPLASTIC AGENTS; ENZYME INHIBITORS; HUMANS; LEUKEMIA, MYELOID, CHRONIC; PIPERAZINES; PROTEIN-TYROSINE KINASES; PROTO-ONCOGENE PROTEINS C-KIT; PYRIMIDINES; RECEPTORS, PLATELET-DERIVED GROWTH FACTOR;

EID: 0036635291     PISSN: 14741776     EISSN: None     Source Type: Journal    
DOI: 10.1038/nrd839     Document Type: Review

References (83)

1. Rowley, J. D. A new consistent abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and giemsa staining. Nature 243, 290-293 (1973).
2. Nowell, P. C. & Hungerford, D. A. A minute chromosome in human chronic granulocytic leukemia. Science 132, 1497 (1960).
3. Bcr/Abl gene of the Philadelphia chromosome. Science 247, 824-830 (1990).
4. Kelliher, M. A. et al. Induction of chronic myelogenous leukemia in mice by the v-Abl and Bcr/Abl. Proc. Natl Acad. Sci. USA 87, 6649-6653 (1990).
5. Heisterkamp, N. et al. Acute leukaemia in Bcr/Abl transgenic mice. Nature 344, 251-253 (1990).
6. Lugo, T G. et al. Tyrosine kinase activity and transformation potency of Bcr-Abl oncogene products. Science 247, 1079-1082 (1990).
7. Lipinsky, C. A. Drug-like properties and the causes of poor solubility and poor permeability. J. Pharmacol. Toxicol. Methods 44, 235-249 (2001).
8. Teague, S. et al. The design of leadlike combinatorial libraries. Angew. Chem. Int. Edn Eng. 38, 3743-3748 (1999).
9. Zimmermann, J. et al. (Phenylamino)pyrimidine (PAP) derivatives: a now class of potent and highly selective PDGF-receptor autophosphorylation inhibitors. Bioorg. Med. Chem. Lett. 6, 1221-1226 (1996).
10. Zimmermann, J. et al. Potent and selective inhibitors of the ABL-kinase: phenylaminopyrimidine (PAP) derivatives. Bioorg. Med. Chem. Lett. 7, 187-192 (1997).
11. Zimmerman, J., Furet, P. & Buchdunger, E. ST1571. A new treatment modality for CML. ACS Symp. Ser. 796, 245-259 (2001).
12. Schindler, T. et al. Structural mechanism for ST1571 inhibition of Abelson tyrosine kinase. Science 289, 1938-1942 (2000).
13. Okuda, K. et al. ARG tyrosine kinase activity is inhibited by ST1571. Blood 97, 2440-2448 (2001).
14. Druker, B. J. et al. Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells. Nature Med. 2, 561-566 (1996).
15. Carroll, M. et al. CGP 57148, a tyrosine kinase inhibitor, inhibits the growth of cells expressing BCR-ABL, TEL-ABL, and TEL-PDGFR fusion proteins. Blood 90, 4947-4952 (1997).
16. Beran, M. et al. Selective inhibition of cell proliferation and BCR-ABL phosphorylation in acute lymphoblastic leukemia cells expressing M, 190,000 BCR-ABL protein by a tyrosine kinase inhibitor (CGP 57148). Clin. Cancer Res. 4, 1661-1672 (1998).
17. Gambacorti-Passerini, C. et al Inhibition of the ABL kinase activity blocks the proliferation of BCR/ABL + leukemic cells and induces apoptosis. Blood Cells Mol. Dis. 23, 380-394 (1997).
18. Deininger, M. et al. The tyrosine kinase inhibitor CGP57148B selectively inhibits the growth of BCR-ABL-positive cells. Blood 90, 3691-3698 (1997).
19. Dan, S., Naito, M. & Tsuruo, T. Selective induction of apoptosis in Philadelphia chromosome-positive chronic myelogenous leukemia cells by an inhibitor of BCR-ABL tyrosine kinase, CGP 57148B. Cell Death Differ. 5, 710-715 (1998).
20. Le Coutre, P. et al. In vivo eradication of human BCR/ABL-positive leukemia cells with an ABL kinase inhibitor. J. Natl Cancer Inst. 91, 163-168 (1999).
21. Wolff, N. C. & Ilaria, R. L. Establishment of a murine model for therapy-treated chronic myelogenous leukemia using the tyrosine kinase inhibitor ST1571. Blood 98, 2808-2816 (2001).
22. Sillaber, C. et al. STAT5 activation contributes to growth and viability in Bcr/Abl-transformed cells. Blood 95, 2118-2125 (2000).
23. L. J. Exp. Med. 191, 977-984 (2000).
24. Oda, T. et al. CrkI is the major tyrosine-phosphorylated protein in neutrophils from patients with chronic myelogenous leukemia. J. Biol. Chem. 269, 22925-22928 (1994).
25. Jonuleit, T. et al. Bcr-Abl kinase downregulates cyclin-dependent kinase inhibitor p27 in human and murine cell lines. Blood 96, 1933-1939 (2000).
26. Gesbert, F. et al. BCR/ABL regulates expression of the cyclin dependent kinase inhibitor p27Kip1 through the PI3K/AKT pathway. J. Biol. Chem. 50, 39223-39230 (2000).
27. Gaston, I. et al. Abl kinase but not PI3-kinase links to the cytoskeletal defects in Bcr-Abl transformed cells. Exp. Hematol. 28, 77-86 (2000).
28. Druker, B. J. et al. 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. 344, 1038-1042 (2001).
29. Druker, B. J. et al. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N. Engl. J. Med. 344, 1031-1037 (2001).
30. Peng, B. et al. Clinical investigation of the PK/PD relationship for Glivec (STI571): a novel inhibitor of signal transduction. Proc. Am. Soc. Clin. Oncol. 20, 280 (2001).
31. Kantarjian, H. et al. Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia. N. Engl. J. Med. 346, 645-652 (2002).
32. Talpaz, M. et al. Glivec™ (imatinib mesylate) induces durable hematologic and cytogenetic responses in patients with accelerated phase chronic myeloid leukemia: results of a Phase 2 study. Blood 99, 1928-1937 (2002).
33. Sawyers, C. et al. Imatinib induces hematologic and cytogenetic responses in patients with chronic myeloid leukemia in myeloid blast crisis: results of a Phase II study. Blood 99, 3530-3539 (2002).
34. Weisberg, E. & Griffin, J. Mechanism of resistance to the Abl tyrosine kinase inhibitor STI571 in BCR/ABL transformed hematopoietic cell lines. Blood 95, 3498-3505 (2000).
35. Mahon, F. et al. Selection and characterization of BCR-ABL positive cell lines with differential sensitivity to the tyrosine kinase inhibitor ST1571: diverse mechanisms of resistance. Blood 96, 1070-1079 (2000).
36. Le Coutre, P. et al. Induction of resistance to the Abelson inhibitor STI571 in human leukemic cells through gene amplification. Blood 95, 1758-1766 (2000).
37. Gorre, M. E. et al. Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science 293, 876-880 (2001).
38. Gorre, M. E. et al. Roots of clinical resistance to STI-571 cancer therapy. Science 293, 2163a (2001).
39. Barthe, C. et al. Roots of clinical resistance to STI-571 cancer therapy. Science 293, 2163a (2001).
40. Hochhaus, A. et al. Roots of clinical resistance to STI-571 cancer therapy. Science 293, 2163a (2001).
41. Von Bubnoff, N. et al. BCR-ABL gene mutations in relation to clinical resistance of Philadelphia-chromosome-positive leukaemia to STI571: a prospective study. Lancet 359, 487-491 (2002).
42. Manley, P. W. et al. Molecular interactions between Gleevec™ and isoforms of the c-Abl kinase. Proc. Am. Assoc. Cancer Res. 4196 (2002).
43. + leukemic cells to STI571. J. Natl Cancer Inst. 92, 1641-1650 (2000).
44. 1-Acid glycoprotein expressed in the plasma of chronic myeloid leukemia patients does not mediate significant in vitro resistance to STI571. Blood 99, 713-715 (2002).
45. Hofmann, W. K. et al. Relation between resistance of Philadelphia-chromosome-positive acute lymphoblastic leukaemia to the tyrosine kinase inhibitor STI571 and gene-expression profiles: a gene-expression study. Lancet 359, 481-486 (2002).
46. + cytarabine as initial therapy for patients with CML: results of a randomized study. Proc. Am. Soc. Clin. Oncol. 1 (2002).
47. Buchdunger, E. et al. The Abl protein-tyrosine kinase inhibitor, STI571, inhibits in vitro signal transduction mediated by c-Kit and PDGF receptors. J. Pharmacol. Exp. Ther. 295, 139-145 (2000).
48. Heinrich, M. C. et al. inhibition of c-kit receptor tyrosine kinase activity by STI571, a selective tyrosine kinase inhibitor. Blood 96, 925-932 (2000).
49. Hirota, S. et al. Gain of function mutations of c-Kit in human gastrointestinal stromal tumors. Science 279, 577-580 (1998).
50. Lasota, J. et al. Mutations in exons 9 and 13 of Kit gene are rare events in gastrointestinal stromal tumors. A study of two hundred cases. Am. J. Pathol. 157, 1091-1095 (2000).
51. Lux, M. L. et al. Kit extracellular and kinase domain mutations in gastrointestinal stromal tumors. Am. J. Pathol. 156, 791-795 (2000).
52. Rubin, B. P. et al. Kit activation is a ubiquitous feature of gastrointestinal stromal tumors. Cancer Res. 61, 8118-8121 (2001).
53. Heinrich, M. C. et al. STI571 inhibits the kinase activity of wild type and juxtamembrane c-Kit mutants but not the exon 17 D816V mutations associated with mastocytosis. Blood 96, 4459 (2000).
54. Tuveson, D. A. et al. STI571 inactivation of the gastrointestinal stromal tumor c-KIT oncoprotein: biological and clinical implications. Oncogene 20, 5054-5058 (2001).
55. Joensuu, H. et al. Effect of the tyrosine kinase inhibitor STI571 in a patient with metastatic gastrointestinal stromal tumor. N. Engl. J. Med. 344, 1052-1056 (2001).
56. Van Oosterom, A. T. et al. Safety and efficacy of imatinib (STI571) in metastatic gastrointestinal stromal tumors, a phase I study. Lancet 358, 1421-1423 (2001).
57. Blanke, C. D. et al. Evaluation of the safety and efficacy of an oral molecularly-targeted therapy, STI571, in patients with unresectable or metastatic gastrointestinal stromal tumors (GISTs) expressing c-KIT (CD117). Proc. Am. Soc. Clin. Oncol. 20, 1 (2001).
58. Heinrich, M. C. et al. Inhibition of Kit kinase activity: a novel molecular approach to the treatment of Kit-positive malignancies. J. Clin. Oncol. 20, 1692-1703 (2002).
59. Krystal, G. W., Hines, S. & Organ, C. Autocrine growth of small cell lung cancer mediated by co-expression of c-kit and stem cell factor. Cancer Res. 56, 370-376 (1996).
60. Krystal, G. W., Carlson, P. & Litz, J. Induction of apoptosis and inhibition of small cell lung cancer growth by the quinoxaline tyrophostins. Cancer Res. 57, 2203-2208 (1997).
61. Krystal, G. W. et al. The selective tyrosine kinase inhibitor STI571 inhibits small cell lung cancer growth. Clin. Cancer Res. 6, 3319-3326 (2000).
62. Wang, W. L. et al. Growth inhibition and modulation of kinase pathways of small cell lung cancer lines by the novel tyrosine kinase inhibitor STI571. Oncogene 19, 3521-3528 (2000).
63. Buchdunger, E. et al. Effects of a selective inhibitor of the Abl tyrosine-kinase in vitro and in vivo by a 2-phenylaminopyrimidine derivative. Cancer Res. 56, 100-104 (1996).
64. Östman, A. & Heldin, C. H. Involvement of platelet-derived growth factor in disease: development of specific antagonists. Adv. Cancer Res. 80, 1-38 (2001).
65. Nistér, M. et al. Differential expression of platelet-derived growth factor receptors in human malignant glioma cell lines. J. Biol. Chem. 266, 16755-16763 (1991).
66. Kilic, T. et al. Intracranial inhibition of platelet-derived growth factor-mediated glioblastoma cell growth by an orally active kinase inhibitor of the 2-phenylaminopyridine class. Cancer Res. 60, 5143-5150 (2000).
67. Shimizu, A. et al. The dermatofibrosarcoma protuberans-associated collagen type 1α/platelet-derived growth factor (PDGF) B-chain fusion gene generates a transforming protein that is processed to functional PDGF-BB. Cancer Res. 59, 3719-3723 (1999).
68. Greco, A. et al. Growth inhibitory effect of STI571 on cells transformed by the COL1A/PDGFB rearrangement. Int. J. Cancer 92, 354-360 (2001).
69. Sjöblom, T. et al. Growth inhibition of dermatofibrosarcoma protuberans tumors by the platelet-derived growth factor receptor antagonist STI571 through induction of apoptosis. Cancer Res. 61, 5778-5783 (2001).
70. Awan, R. A. et al. Patients with metastatic sarcoma arising from dermatofibrosarcoma protuberans (DFSP) may respond to imatinib (STI571, Gleevec). Proc. Am. Soc. Clin. Oncol. 1637 (2002).
71. Jousset, C. et al. A domain of TEL conserved in a subset of ETS proteins defines a specific oligomerization interface essential to the mitogenic properties of the TEL-PDGFRβ oncoprotein. EMBO J. 16, 69-82 (1997).
72. Tomasson, M. H. et al. TEL/PDGFβR induces hematologic malignancies in mice that respond to a specific tyrosine kinase inhibitor. Blood 93, 1707-1714 (1999).
73. Apperley, J. F. et al. Chronic myeloproliferative diseases with t(5:12) and a PDGFRB fusion gene: complete cytogenetic remission with STI571. Blood 98, 726A (2001).
74. Gullberg, D. et al. β1 Integrin-mediated collagen gel contraction is stimulated by PDGF Exp. Cell Res. 186, 264-272 (1990).
75. Rodt, S. A. et al. A novel physiologic role for platelet-derived growth factor-BB in rat dermis. J. Physiol. (Lond.) 495, 193-200 (1996).
76. Heuchel, R. et al. Platelet-derived growth factor receptor regulates interstitial fluid homeostasis through phosphatidylinositol-3 kinase signaling. Proc. Natl Acad. Sci. USA. 20, 11410-11415 (1999).
77. Jain, R. K. Delivery of molecular medicine to solid tumors. Science 271, 1079-1080 (1996).
78. Pietras, K. et al. Inhibition of platelet-derived growth factor receptors reduces interstitial hypertension and increases transcapillary transport in tumors. Cancer Res. 61, 2929-2934 (2001).
79. Hellström, M. et al. Role of PDGF-B and PDGFR-β in recruitment of vascular smooth muscle cells and pericytes during embryonic blood vessel formation in the mouse. Exp. Cell Res. 186, 264-272 (1999).
80. Reinmuth, N. et al. Induction of VEGF in perivascular cells defines a potential paracrine mechanism for endothelial cell survival. FASEB J. 15, 1239-1241 (2001).
81. Wang, D. et al. Induction of vascular endothelial growth factor expression in endothelial cells by platelet-derived growth factor through the activation of phosphatidylinositol 3-kinase. Cancer Res. 59, 1464-1472 (1999).
82. Buchdunger, E., O'Reilly, T. & Wood, J. Pharmacology of imatinib (STI571). Eur. J. Cancer (in the press).
83. Uehara, H. et al. Blockade of PDGF-R signaling by STI571 inhibits angiogenesis and growth of human prostate cancer cells in the bone of nude mice. Proc. Am. Assoc. Cancer Res. 2192 (2001).