Activating Death Receptor DR5 as a Therapeutic Strategy for Rhabdomyosarcoma

• DOI: 10.5402/2012/395952
• Publication Date: 2012-04-19T10:59:44Z
• Authors: Zhigang Kang; Shi-Yong Sun; Liang Cao
• Keywords: 0301 basic medicine; 03 medical and health sciences; Review Article; 3. Good health

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 asMYOD1andmyogenin. 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 thep53tumor suppressor gene. However, the ability to induce apoptosis via the death receptor-dependent extrinsic pathway remains largely intact in tumors withp53mutations. 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.