Improving the Efficacy of Retinoid Therapy in Childhood Neuroblastoma

癌症仍然是导致儿童死亡的最常见疾病。儿童神经母细胞瘤是一种神经组织癌症，通常表现为广泛传播的恶性肿瘤，对常规治疗反应不佳，表明需要新的治疗方法。维生素A衍生物或类维生素A，在常规治疗的基础上，可将晚期神经母细胞瘤患儿的治愈率提高到50%。我们已经表明，类维生素A耐药的一个可能机制是缺乏视黄酸受体β，这是一个必要的因素，在神经母细胞瘤细胞转化为一个不可逆的细胞变化的类维生素A抗癌信号。在这个项目中，我们将确定为什么一些神经母细胞瘤细胞表达低水平的这种蛋白质，并测试新的类维生素A疗法。

Cancer is still the commonest disease causing death in chilhood. Childhood neuroblastoma is a cancer of the nerve tissue which presents usually as a widely spread malignancy, which responds poorly to conventional therapy, indicating the need for novel treatment approaches. Vitamin A derivatives, or retinoids, given in addition to conventional therapy improves the cure rate for children with advanced neuroblastoma to 50%. We have shown that one likely mechanism of retinoid resistance is a deficiency of retinoic acid receptor beta, which is a necessary factor in the neuroblastoma cell for converting the retinoid anti-cancer signal into an irreversible cellular change. In this project we will define why some neuroblastoma cells express low levels of this protein and test new retinoid therapies.