Novel targeted agents for platelet-derived growth factor receptor and c-KIT in malignant gliomas Journal Article
| Authors: | Morris, P. G.; Abrey, L. E. |
| Article Title: | Novel targeted agents for platelet-derived growth factor receptor and c-KIT in malignant gliomas |
| Abstract: | Malignant gliomas are a heterogeneous group of tumors with a varying natural history and response to treatment. Despite current therapeutic strategies, these tumors almost universally recur after excision and are associated with a poor survival. Increasingly, the true heterogeneity of these tumors is being correlated with distinct molecular subgroups. Platelet-derived growth factor receptor (PDGFR) alpha is almost universally expressed on glioma cells; expression of the proto-oncogene c-KIT has also been reported. These findings have led to the clinical investigation of inhibitors of this pathway, such as imatinib and dasatinib, for the treatment of recurrent malignant glioma. To date, this approach in unselected patients has been disappointing. However, isolated responses have been seen, which may correlate with constitutive activation of one or more of the corresponding tyrosine kinases. In the future, it is hoped that an increasing knowledge of glioma biology will translate into the more judicious use of these and other targeted therapies, resulting in improvements in patient outcomes. This review describes the preclinical science behind PDGFR and c-KIT, the clinical importance of these molecular pathways and the available data from translational clinical trials. © 2010 Springer-Verlag. |
| Keywords: | signal transduction; cancer survival; protein expression; treatment outcome; hydroxyurea; clinical trial; disease course; fatigue; review; cancer recurrence; sorafenib; bevacizumab; sunitinib; nonhuman; antineoplastic agents; clinical trials as topic; drug targeting; disease free survival; temozolomide; glioma; neurosurgery; brain neoplasms; c-kit; imatinib; platelet derived growth factor alpha receptor; stem cell factor receptor; proto-oncogene proteins c-kit; multiple cycle treatment; antineoplastic activity; cancer cell culture; enzyme activation; dasatinib; platelet derived growth factor receptor; protein tyrosine kinase; disease model; drug research; glioma cell; glioblastoma; targeted therapy; tumor bleeding; hematologic disease; receptors, platelet-derived growth factor; platelet derived growth factor beta receptor; malignant glioma; platelet-derived growth factor receptor (pdgfr); 5 [(5 fluoro 1,2 dihydro 2 oxo 3h indol 3 ylidene)methyl] n (2 hydroxy 3 morpholinopropyl) 2,4 dimethyl 1h pyrrole 3 carboxamide; midostaurin; tandutinib |
| Journal Title: | Targeted Oncology |
| Volume: | 5 |
| Issue: | 3 |
| ISSN: | 1776-2596 |
| Publisher: | Springer |
| Date Published: | 2010-09-01 |
| Start Page: | 193 |
| End Page: | 200 |
| Language: | English |
| DOI: | 10.1007/s11523-010-0160-7 |
| PUBMED: | 20844972 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Export Date: 20 April 2011" - "Source: Scopus" |
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