Molecular targeting therapies for neuroblastoma: Progress and challenges.
Molecular targeting therapies for neuroblastoma: Progress and challenges.
复制标题
神经母细胞瘤的分子靶向治疗：进展和挑战。
DOI：
10.1002/med.21750
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发表时间：
2021-03
影响因子：
13.3
通讯作者：
Zhang R
中科院分区：
文献类型：
--
作者：
Zafar A;Wang W;Liu G;Wang X;Xian W;McKeon F;Foster J;Zhou J;Zhang R
迫切需要为儿童癌症寻找新的治疗方法。神经母细胞瘤是儿科最常见的实体瘤，约占儿童癌症相关死亡率的15%。神经母细胞瘤表现出遗传、形态和临床上的异质性，这限制了现有治疗方法的疗效。获得神经母细胞瘤发病机制中涉及的分子特征和遗传变异的详细知识对于开发这种毁灭性疾病的更安全和更有效的治疗方法是必要的。最近用先进的高通量“组学”技术进行的研究揭示了许多遗传/基因组改变和功能障碍的途径，这些改变和功能障碍推动了神经母细胞瘤的发生、生长、进展和对治疗的抵抗。人们正在评估各种分子标记，以更好地了解这种疾病，其中许多分子标记被用作开发神经母细胞瘤患者的新治疗方法的靶点。本文综述了MYCN、BIRC5、PHOX2B和Lin28b等参与神经母细胞瘤发病机制的分子通路和遗传异常的研究现状，并对临床前和临床研究中的分子靶向治疗进行了综述，特别是针对ALK信号、MDM2、PI3K/Akt/mTOR和Ras-MAPK通路以及表观遗传调节因子的分子靶向治疗。我们还对涉及针对各种途径的新型制剂的联合疗法的使用提出了见解。此外，我们讨论了未来的方向，这将有助于确定新的靶点和治疗方法，并改进现有的治疗方法，提高神经母细胞瘤患者的治疗结果和存活率。
There is an urgent need to identify novel therapies for childhood cancers. Neuroblastoma is the most common pediatric solid tumor, and accounts for ~15% of childhood cancer‐related mortality. Neuroblastomas exhibit genetic, morphological and clinical heterogeneity, which limits the efficacy of existing treatment modalities. Gaining detailed knowledge of the molecular signatures and genetic variations involved in the pathogenesis of neuroblastoma is necessary to develop safer and more effective treatments for this devastating disease. Recent studies with advanced high‐throughput “omics” techniques have revealed numerous genetic/genomic alterations and dysfunctional pathways that drive the onset, growth, progression, and resistance of neuroblastoma to therapy. A variety of molecular signatures are being evaluated to better understand the disease, with many of them being used as targets to develop new treatments for neuroblastoma patients. In this review, we have summarized the contemporary understanding of the molecular pathways and genetic aberrations, such as those in MYCN, BIRC5, PHOX2B, and LIN28B, involved in the pathogenesis of neuroblastoma, and provide a comprehensive overview of the molecular targeted therapies under preclinical and clinical investigations, particularly those targeting ALK signaling, MDM2, PI3K/Akt/mTOR and RAS‐MAPK pathways, as well as epigenetic regulators. We also give insights on the use of combination therapies involving novel agents that target various pathways. Further, we discuss the future directions that would help identify novel targets and therapeutics and improve the currently available therapies, enhancing the treatment outcomes and survival of patients with neuroblastoma.
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影响因子：
0.8
作者：
Applebaum MA;Desai AV;Glade Bender JL;Cohn SL
通讯作者：
Cohn SL
DOI：
10.1158/1078-0432.ccr-08-1815
发表时间：
2009-05-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Brodeur GM;Minturn JE;Ho R;Simpson AM;Iyer R;Varela CR;Light JE;Kolla V;Evans AE
通讯作者：
Evans AE
影响因子：
3
作者：
Iyer, Radhika;Varela, Carly R.;Minturn, Jane E.;Ho, Ruth;Simpson, Anisha M.;Light, Jennifer E.;Evans, Audrey E.;Zhao, Huaqing;Thress, Kenneth;Brown, Jeffrey L.;Brodeur, Garrett M.
通讯作者：
Brodeur, Garrett M.
影响因子：
3.7
作者：
Bachetti, Tiziana;Di Paolo, Daniela;Perri, Patrizia
通讯作者：
Perri, Patrizia
影响因子：
5.8
作者：
Aveic S;Pantile M;Polo P;Sidarovich V;De Mariano M;Quattrone A;Longo L;Tonini GP
通讯作者：
Tonini GP