| Abstract: |
Molecularly targeted therapies hold the promise of providing new anticancer treatments that are more effective and less toxic than traditional cytotoxic chemotherapy. Unfortunately, results of first generation targeted therapy trials for malignant gliomas (glioblastomas and anaplastic forms of astrocytomas, oligodendrogliomas and oligoastrocytomas) have been disappointing. While combination strategies targeting angiogenesis through inhibition of the VEGFR pathway (eg, bevacizumab combined with irinotecan) have demonstrated promising activity, single-agent drugs have been largely unsuccessful when tested in recurrent disease clinical trials. These single agents include EGF receptor tyrosine kinase inhibitors (gefitinib and erlotinib), PDGF receptor inhibitors (imatinib), mTOR inhibitors (temsirolimus and everolimus), and VEGFR, protein kinase C-β and other angiogenesis pathway inhibitors (vatalanib and enzastaurin). A new generation of trials is seeking to define whether inhibiting multiple targets simultaneously through utilization of less specific, multi-targeting drugs, or through combination of two or more single-targeted drugs, can overcome tumor resistance. In this review, the rationale and challenges of developing such multi-targeted strategies in gliomas are presented. © Thomson Reuters (Scientific) Ltd. |
| Keywords: |
cancer chemotherapy; hydroxyurea; clinical trial; review; sorafenib; bevacizumab; erlotinib; raf protein; clinical trials as topic; receptors, vascular endothelial growth factor; drug targeting; temozolomide; glioma; imatinib; antineoplastic combined chemotherapy protocols; epidermal growth factor receptor; combination chemotherapy; receptor, epidermal growth factor; drug structure; dasatinib; platelet derived growth factor receptor; angiogenesis; neovascularization, pathologic; cetuximab; irinotecan; temsirolimus; glioblastoma; mammalian target of rapamycin; gefitinib; pazopanib; vandetanib; vatalanib; oligodendroglioma; targeted therapy; molecular structure; combination therapy; drugs, investigational; astrocytoma; gliosarcoma; everolimus; rapamycin; lapatinib; enzastaurin; vasculotropin receptor 1; receptors, platelet-derived growth factor; vegf; egf; pdgf
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