[Tyrosine kinase inhibitor STI571: new possibility in the treatment of chronic myeloid leukemia] - PubMed

[Article in Hungarian]

Affiliations

• PMID: 12440260

Review

[Tyrosine kinase inhibitor STI571: new possibility in the treatment of chronic myeloid leukemia]

[Article in Hungarian]

Lenke Molnár et al. Orv Hetil. 2002.

Abstract

Chronic myeloid leukemia shown to be associated with the Ph translocation,--characterised as a t(9;22)--, joins the bcr and abl genes and leads to expression of chimeric BCR-ABL protein with enhanced tyrosine kinase (TK) activity. This increased TK activity leads to malignant transformation by interference with the control of proliferation, cellular adherence and apoptosis. The presence of this protein in every CML cells is strong evidence of its pathogenetic role. Following this observations efforts were made to develop molecularly targeted therapies for CML. The specific inhibitor of BCR-ABL TK, STI571 was developed by Brian Druker and his co-workers in 1996. STI571 (Signal Transduction Inhibitor) occupies the kinase pocket of the BCR-ABL protein, and blocks ATP binding, thereby preventing phosphorylation of any substrate. Because of promising preclinical data STI571 entered clinical trials in 1998, using an oral formulation. The reports of this trials document excellent efficacy. Patients with chronic phase after failure with interferon therapy achieved more than 90% hematologic response, usually within 4-6 weeks, and 55% major cytogenetic response. Patients with advanced disease also responded, though less durably. In phase 2 studies the drug has continued to produce impressive results. STI571 has a very favourable pharmacologic feature, with high degree of specificity for its target, and therefore low toxicity for normal tissues, it is well tolerable, side effects were minimal. STI571 opens a new era in the treatment of malignancies, it is the first targeted molecular therapy which is able to target abnormal cells without damaging normal cells, compared with traditional antineoplastic drugs.

Similar articles

• Inhibition of phosphotyrosine phosphatase 1B causes resistance in BCR-ABL-positive leukemia cells to the ABL kinase inhibitor STI571.

  Koyama N, Koschmieder S, Tyagi S, Portero-Robles I, Chromic J, Myloch S, Nürnberger H, Rossmanith T, Hofmann WK, Hoelzer D, Ottmann OG. Koyama N, et al. Clin Cancer Res. 2006 Apr 1;12(7 Pt 1):2025-31. doi: 10.1158/1078-0432.CCR-04-2392. Clin Cancer Res. 2006. PMID: 16609011

• [Molecular targeted treatment--new treatment strategy for patients with chronic myeloid leukemia].

  Usui N. Usui N. Rinsho Byori. 2004 Feb;52(2):136-44. Rinsho Byori. 2004. PMID: 15027317 Review. Japanese.

• [STI571 (Glivec)--a new drug for the treatment of chronic myeloid leukemia].

  Hasselbalch HC. Hasselbalch HC. Ugeskr Laeger. 2002 May 27;164(22):2914-7. Ugeskr Laeger. 2002. PMID: 12082821 Review. Danish.

• Selective pyrrolo-pyrimidine inhibitors reveal a necessary role for Src family kinases in Bcr-Abl signal transduction and oncogenesis.

  Wilson MB, Schreiner SJ, Choi HJ, Kamens J, Smithgall TE. Wilson MB, et al. Oncogene. 2002 Nov 21;21(53):8075-88. doi: 10.1038/sj.onc.1206008. Oncogene. 2002. PMID: 12444544

• Imatinib mesylate (STI571) abrogates the resistance to doxorubicin in human K562 chronic myeloid leukemia cells by inhibition of BCR/ABL kinase-mediated DNA repair.

  Majsterek I, Sliwinski T, Poplawski T, Pytel D, Kowalski M, Slupianek A, Skorski T, Blasiak J. Majsterek I, et al. Mutat Res. 2006 Jan 31;603(1):74-82. doi: 10.1016/j.mrgentox.2005.10.010. Epub 2006 Jan 4. Mutat Res. 2006. PMID: 16388976

Cited by

• Computational healthcare: Present and future perspectives (Review).

  Asai A, Konno M, Taniguchi M, Vecchione A, Ishii H. Asai A, et al. Exp Ther Med. 2021 Dec;22(6):1351. doi: 10.3892/etm.2021.10786. Epub 2021 Sep 23. Exp Ther Med. 2021. PMID: 34659497 Free PMC article. Review.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Medical

  • MedlinePlus Health Information

• Miscellaneous

  • NCI CPTAC Assay Portal