Activating Death Receptor DR5 as a Therapeutic Strategy for Rhabdomyosarcoma.
Activating Death Receptor DR5 as a Therapeutic Strategy for Rhabdomyosarcoma.
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DOI：
10.5402/2012/395952
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Cao L
中科院分区：
文献类型：
--
作者：
Kang Z;Sun SY;Cao L
横纹肌肉瘤是儿童最常见的软组织肉瘤。它被认为来自骨骼肌祖细胞，保留了对胚胎肌源性发育至关重要的基因的表达，如MYOD 1和肌细胞生成素。RMS被分类为胚胎型，在年幼的儿童中更常见，或肺泡型，在年长的儿童和成人中更常见。尽管积极的管理，包括手术，放疗和化疗，儿童转移性RMS的结果是令人沮丧的，预后几十年来一直保持不变。细胞凋亡是一个高度调控的过程，对胚胎发育和组织器官的稳态至关重要。与其他类型的癌症一样，RMS通过p53肿瘤抑制基因突变逃避内在凋亡而发展。然而，通过死亡受体依赖性外源性途径诱导细胞凋亡的能力在具有p53突变的肿瘤中基本上保持完整。本文着重于激活外源性凋亡作为RMS的治疗策略，通过靶向死亡受体DR5与重组TRAIL配体或激动性抗体直接针对DR5。
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.