Abstract
Kit a type III receptor tyrosine kinase, along with its ligand the stem cell factor, play a critical role in normal cell growth, differentiation, development and survival. Ligand independent activation of kit (dysregulated kit function) has been found to be an important component of oncogenesis in a large number of neoplastic disorders such as systemic mastocytosis, gastro intestinal stromal tumors, germ cell tumors, acute myelogenous leukemia with the disruption of the core binding factor, amongst others. The identification of small molecule inhibitors with activity against Kit, has offered a wider and more effective range of therapeutic options in the treatment of these neoplastic processes. Novel tyrosine kinase inhibitors such as imatinib, nilotinib and dasatinib, have been found to be effective in the management of various subtypes of systemic mastocytosis and gastrointestinal stromal tumors. Non-tyrosine kinase inhibitors like rapamycin, 17-AAG and IMD- 0354 have been added to the therapeutic armamentarium, with the hope that combination therapy might have a synergistic effect, or prevent/delay the development of drug resistance.
Keywords: Receptor tyrosine kinases, hematopoesis, stem cell factor, Systemic Mastocytosis, Dasatinib, Gastrointestinal stromal cell tumors
Current Cancer Drug Targets
Title: Kit: Molecule of Interest for the Diagnosis and Treatment of Mastocytosis and other Neoplastic Disorders
Volume: 7 Issue: 5
Author(s): Mrinal M. Patnaik, Ayalew Tefferi and Animesh Pardanani
Affiliation:
Keywords: Receptor tyrosine kinases, hematopoesis, stem cell factor, Systemic Mastocytosis, Dasatinib, Gastrointestinal stromal cell tumors
Abstract: Kit a type III receptor tyrosine kinase, along with its ligand the stem cell factor, play a critical role in normal cell growth, differentiation, development and survival. Ligand independent activation of kit (dysregulated kit function) has been found to be an important component of oncogenesis in a large number of neoplastic disorders such as systemic mastocytosis, gastro intestinal stromal tumors, germ cell tumors, acute myelogenous leukemia with the disruption of the core binding factor, amongst others. The identification of small molecule inhibitors with activity against Kit, has offered a wider and more effective range of therapeutic options in the treatment of these neoplastic processes. Novel tyrosine kinase inhibitors such as imatinib, nilotinib and dasatinib, have been found to be effective in the management of various subtypes of systemic mastocytosis and gastrointestinal stromal tumors. Non-tyrosine kinase inhibitors like rapamycin, 17-AAG and IMD- 0354 have been added to the therapeutic armamentarium, with the hope that combination therapy might have a synergistic effect, or prevent/delay the development of drug resistance.
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Mrinal M. Patnaik , Ayalew Tefferi and Animesh Pardanani , Kit: Molecule of Interest for the Diagnosis and Treatment of Mastocytosis and other Neoplastic Disorders, Current Cancer Drug Targets 2007; 7 (5) . https://dx.doi.org/10.2174/156800907781386614
DOI https://dx.doi.org/10.2174/156800907781386614 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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