Table of Contents
ISRN Oncology
Volume 2012, Article ID 395952, 10 pages
Review Article

Activating Death Receptor DR5 as a Therapeutic Strategy for Rhabdomyosarcoma

1Genetics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA
2Laboratory of Proteomics and Analytical Technologies, SAIC-Frederick, Inc., NCI Frederick, Frederick, MD 21702, USA
3Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322, USA

Received 4 January 2012; Accepted 24 January 2012

Academic Editors: E. Boven and S. Mandruzzato

Copyright © 2012 Zhigang Kang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children. It is believed to arise from skeletal muscle progenitors, preserving the expression of genes critical for embryonic myogenic development such as MYOD1 and myogenin. RMS is classified as embryonal, which is more common in younger children, or alveolar, which is more prevalent in elder children and adults. Despite aggressive management including surgery, radiation, and chemotherapy, the outcome for children with metastatic RMS is dismal, and the prognosis has remained unchanged for decades. Apoptosis is a highly regulated process critical for embryonic development and tissue and organ homeostasis. Like other types of cancers, RMS develops by evading intrinsic apoptosis via mutations in the p53 tumor suppressor gene. However, the ability to induce apoptosis via the death receptor-dependent extrinsic pathway remains largely intact in tumors with p53 mutations. This paper focuses on activating extrinsic apoptosis as a therapeutic strategy for RMS by targeting the death receptor DR5 with a recombinant TRAIL ligand or agonistic antibodies directed against DR5.