John M Magenau1, Scott M Schuetze. 1. Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
Abstract
PURPOSE OF REVIEW: Systemic treatment options for advanced sarcoma remain limited. Emerging trends exploring targeted therapy for the treatment of sarcoma are reviewed here. RECENT FINDINGS: Effective treatments for metastatic sarcoma after the failure of front line regimens, such as doxorubicin, ifosfamide, and gemcitabine with docetaxel, are clearly limited. Translational research has identified a significant proportion of sarcomas with characteristic molecular changes potentially amenable to targeted therapy. Aberrant signaling of mammalian target of rapamycin and tyrosine kinase pathways have been focal points of recent research. Early trials investigating biologic inhibitors of these pathways have yielded varied clinical results. Agents targeting stem cell factor receptor (C-KIT), platelet-derived growth factor receptor, mammalian target of rapamycin, and vascular endothelial growth factor receptor have all shown efficacy to some degree in advanced sarcoma. The insulinlike growth factor-1 receptor is a potentially important target for sarcoma treatment based on early clinical results. SUMMARY: Sarcomas are a heterogeneous group of tumors and targeted agents likely have a long-term role in their treatment. Identifying critical pathways in sarcomagenesis, susceptible subtypes and developing novel combinations remain the focus of future research.
PURPOSE OF REVIEW: Systemic treatment options for advanced sarcoma remain limited. Emerging trends exploring targeted therapy for the treatment of sarcoma are reviewed here. RECENT FINDINGS: Effective treatments for metastatic sarcoma after the failure of front line regimens, such as doxorubicin, ifosfamide, and gemcitabine with docetaxel, are clearly limited. Translational research has identified a significant proportion of sarcomas with characteristic molecular changes potentially amenable to targeted therapy. Aberrant signaling of mammalian target of rapamycin and tyrosine kinase pathways have been focal points of recent research. Early trials investigating biologic inhibitors of these pathways have yielded varied clinical results. Agents targeting stem cell factor receptor (C-KIT), platelet-derived growth factor receptor, mammalian target of rapamycin, and vascular endothelial growth factor receptor have all shown efficacy to some degree in advanced sarcoma. The insulinlike growth factor-1 receptor is a potentially important target for sarcoma treatment based on early clinical results. SUMMARY:Sarcomas are a heterogeneous group of tumors and targeted agents likely have a long-term role in their treatment. Identifying critical pathways in sarcomagenesis, susceptible subtypes and developing novel combinations remain the focus of future research.
Authors: Martin G Belinsky; Lori Rink; Kathy Q Cai; Michael F Ochs; Burton Eisenberg; Min Huang; Margaret von Mehren; Andrew K Godwin Journal: Cell Cycle Date: 2008-10-07 Impact factor: 4.534