New strategies in refractory and recurrent neuroblastoma: translational opportunities to impact patient outcome.
New strategies in refractory and recurrent neuroblastoma: translational opportunities to impact patient outcome.
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DOI：
10.1158/1078-0432.ccr-11-1409
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发表时间：
2012-05-01
期刊：
影响因子：
--
通讯作者：
Maris JM
中科院分区：
文献类型：
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作者：
Cole KA;Maris JM
尽管最近在了解肿瘤发生和发展的遗传基础方面取得了重大进展，但神经母细胞瘤仍然是造成儿童癌症发病率和死亡率不成比例的原因。大约一半的新诊断患者可以可靠地确定为患有低恶性潜能的肿瘤，这些儿童在很少或没有细胞毒性治疗的情况下治愈率大于95%。另一方面，另一半的神经母细胞瘤通常以爆炸性的方式出现，伴有广泛的转移性疾病，并且已经为这种表型定义了可靠的肿瘤特异性生物标志物。高风险神经母细胞瘤治疗的经验方法依赖于化疗剂量强度的急剧增加，最近结合了靶向免疫治疗，但近50%的高风险疾病儿童将难以治疗或复发，这两种情况都是致命的。未来高危神经母细胞瘤预后的改善将需要确定疾病和患者特异性的致癌易感性，从而在治疗上加以利用。神经母细胞瘤治疗新方法的合理发展需要前瞻性的策略，以明确证明在复发环境中的活性，并最终在纳入一线治疗计划时治愈患者。
Neuroblastoma remains responsible for a disproportionate amount of childhood cancer morbidity and mortality despite recent significant advances in understanding the genetic basis of tumor initiation and progression. About half of newly diagnosed patients can be reliably identified as having tumors of low malignant potential, and these children have cure rates of greater than 95% with little or no cytotoxic therapy. On the other hand, the other half of neuroblastomas typically present in an explosive fashion with widely metastatic disease, and reliable tumor-specific biomarkers have been defined for this phenotype as well. Empiric approaches to high-risk neuroblastoma therapy have relied on dramatic escalation of chemotherapy dose intensity, and recently the incorporation of targeted immunotherapy, but nearly 50% of children with high-risk disease will be refractory to therapy or suffer a relapse, both of which are invariably fatal. Future improvements in high-risk neuroblastoma outcomes will require the identification of disease and patient-specific oncogenic vulnerabilities that can be leveraged therapeutically. Rational development of novel approaches to neuroblastoma therapy requires forward-thinking strategies to unequivocally prove activity in the relapse setting, and ultimately efficacy in curing patients when integrated into frontline treatment plans.