Zhou Xia, Wang Xiaokang, Li Nan, Guo Yu, Yang Xiaolin, Lei Yuhe
Shenzhen Hospital of Guangzhou University of Chinese Medicine, Shenzhen, China.
Department of Pharmacy, Shenzhen Longhua District Central Hospital, Shenzhen, China.
Front Pharmacol. 2023 Feb 16;14:1114295. doi: 10.3389/fphar.2023.1114295. eCollection 2023.
Neuroblastoma is one of the most common pediatric solid tumors that threaten the health of children, accounting for about 15% of childhood cancer-related mortality in the United States. Currently, multiple therapies have been developed and applied in clinic to treat neuroblastoma including chemotherapy, radiotherapy, targeted therapy, and immunotherapy. However, the resistance to therapies is inevitable following long-term treatment, leading to treatment failure and cancer relapse. Hence, to understand the mechanisms of therapy resistance and discover reversal strategies have become an urgent task. Recent studies have demonstrated numerous genetic alterations and dysfunctional pathways related to neuroblastoma resistance. These molecular signatures may be potential targets to combat refractory neuroblastoma. A number of novel interventions for neuroblastoma patients have been developed based on these targets. In this review, we focus on the complicated mechanisms of therapy resistance and the potential targets such as ATP-binding cassette transporters, long non-coding RNAs, microRNAs, autophagy, cancer stem cells, and extracellular vesicles. On this basis, we summarized recent studies on the reversal strategies to overcome therapy resistance of neuroblastoma such as targeting ATP-binding cassette transporters, gene, cancer stem cells, hypoxia, and autophagy. This review aims to provide novel insight in how to improve the therapy efficacy against resistant neuroblastoma, which may shed light on the future directions that would enhance the treatment outcomes and prolong the survival of patients with neuroblastoma.
神经母细胞瘤是威胁儿童健康的最常见儿科实体瘤之一，在美国儿童癌症相关死亡率中约占15%。目前，临床上已开发并应用了多种治疗神经母细胞瘤的方法，包括化疗、放疗、靶向治疗和免疫治疗。然而，长期治疗后不可避免地会出现治疗耐药性，导致治疗失败和癌症复发。因此，了解治疗耐药机制并发现逆转策略已成为一项紧迫任务。最近的研究表明，有许多与神经母细胞瘤耐药相关的基因改变和功能失调的通路。这些分子特征可能是对抗难治性神经母细胞瘤的潜在靶点。基于这些靶点，已经为神经母细胞瘤患者开发了一些新的干预措施。在这篇综述中，我们关注治疗耐药的复杂机制以及潜在靶点，如ATP结合盒转运蛋白、长链非编码RNA、微小RNA、自噬、癌症干细胞和细胞外囊泡。在此基础上，我们总结了最近关于克服神经母细胞瘤治疗耐药性的逆转策略的研究，如靶向ATP结合盒转运蛋白、基因、癌症干细胞、缺氧和自噬。这篇综述旨在为如何提高抗耐药神经母细胞瘤的治疗效果提供新的见解，这可能为未来提高治疗效果和延长神经母细胞瘤患者生存期的方向提供启示。
