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Journal Article
Research Support, Non-U.S. Gov't
Review
Engaging Cell Death Pathways for the Treatment of Rhabdomyosarcoma.
Rhabdomyosarcoma (RMS), a malignant neoplasm of presumed mesenchymal origin, is the most common soft tissue cancer of childhood. Despite aggressive treatment, resistance to current therapies remains a challenge. The success of most cytotoxic chemotherapies requires intact programmed cell death (apoptosis) pathways. Defects in the cellular apoptotic program play a key role in the pathogenesis of RMS and contribute to chemotherapeutic resistance to current treatments. Targeting and engaging apoptotic pathways using small-molecule IAP antagonists, death-inducing ligands, reestablishing pannexin channel expression and activity, immunotherapies, or a combination of these approaches is expected to improve outcomes in RMS patients. There is a clear need to better understand the molecular basis of apoptotic resistance in RMS, which may provide an opportunity to identify the patients most likely to benefit from targeted treatments, and for the discovery of novel therapies.
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