Translational research in complex etiopathogenesis and therapy of hematological malignancies: the specific role of tyrosine kinases signaling and inhibition
- 59 Downloads
During the recent genomics and proteomics era, high-resolution, genome-wide approaches have revealed numerous promising new drug targets and disease biomarkers, accelerating and emphasizing the need for targeted molecular therapy compounds. Significant progress has been made in understanding the pathogenesis of hematological malignancies there by, revealing new drug targets. Introduction of multiple new technologies in cancer research have significantly improved the drug discovery process, leading to key success in targeted cancer therapeutics, including tyrosine kinase inhibitors. The studies of receptor tyrosine kinases and their role in malignant transformation are already translated from the preclinical level (cell-based and animal models) to clinical studies, enabling the more complete understanding of tumor cell biology and improvement of tumor therapy.
KeywordsLeukemia Receptor protein–tyrosine kinases Protein kinase inhibitors
This work was supported by the bilateral project of cooperation between the Ministry of Science, Republic of Serbia and CNRS, France, grant No. 451-03-2405/2007-02/12-1.
- 2.Hughes T, et al. Monitoring CML patients responding to treatment with tyrosine kinase inhibitors: review and recommendations for harmonizing current methodology for detecting BCR-ABL transcripts and kinase domain mutations and for expressing results. Blood. 2006;108:28–37. doi: 10.1182/blood-2006-01-0092.CrossRefPubMedGoogle Scholar
- 18.Martelli AM, Tazzari PL, Evangelisti C, Chiarini F, Blalock WL, Billi AM, et al. Targeting the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin module for acute myelogenous leukemia therapy: from bench to bedside. Curr Med Chem. 2007;14:2009–23. doi: 10.2174/092986707781368423.CrossRefPubMedGoogle Scholar
- 19.Nishioka C, Ikezoe T, Yang J, Koeffler HP, Yokoyama A. Blockade of mTOR signaling potentiates the ability of histone deacetylase inhibitor to induce growth arrest and differentiation of acute myelogenous leukemia cells. Leukemia. 2008; doi: 10.1038/leu.2008.243.
- 26.Schittenhelm MM, et al. Dasatinib (BMS-354825), a dual SRC/ABL kinase inhibitor, inhibits the kinase activity of wild-type, juxtamembrane, and activation loop mutant KIT isoforms associated with human malignancies. Cancer Res. 2006;66:473–81. doi: 10.1158/0008-5472.CAN-05-2050.CrossRefPubMedGoogle Scholar
- 30.Knapper S, Mills KI, Gilkes AF, Austin SJ, Walsh V, Burnett AK. The effects of lestaurtinib (CEP701) and PKC412 on primary AML blasts: the induction of cytotoxicity varies with dependence on FLT3 signaling in both FLT3-mutated and wild-type cases. Blood. 2006;108:3494–503. doi: 10.1182/blood-2006-04-015487.CrossRefPubMedGoogle Scholar