University of Oklahoma Health Sciences Center , Oklahoma City, USA.
Stephenson Cancer Center , Oklahoma City, USA.
Expert Opin Ther Targets. 2020 Sep;24(9):899-914. doi: 10.1080/14728222.2020.1790528. Epub 2020 Oct 6.
Neuroblastoma (NB) is the prime cancer of infancy, and accounts for 9% of pediatric cancer deaths. While children diagnosed with clinically stable NB experience a complete cure, those with high-risk disease (HR-NB) do not recover, despite intensive therapeutic strategies. Development of novel and effective targeted therapies is needed to counter disease progression, and to benefit long-term survival of children with HR-NB.
Recent studies (2017-2020) pertinent to NB evolution are selectively reviewed to recognize novel and effective therapeutic targets. The prospective and promising therapeutic targets/strategies for HR-NB are categorized into (a) targeting oncogene-like and/or reinforcing tumor suppressor (TS)-like lncRNAs; (b) targeting oncogene-like microRNAs (miRs) and/or mimicking TS-miRs; (c) targets for immunotherapy; (d) targeting epithelial-to-mesenchymal transition and cancer stem cells; (e) novel and beneficial combination approaches; and (f) repurposing drugs and other strategies in development.
It is highly unlikely that agents targeting a single candidate or signaling will be beneficial for an HR-NB cure. We must develop efficient drug deliverables for functional targets, which could be integrated and advance clinical therapy. Fittingly, the looming evidence indicated an aggressive evolution of promising novel and integrative targets, development of efficient drugs, and improvised strategies for HR-NB treatment.
神经母细胞瘤(NB)是婴儿期的主要癌症,占儿童癌症死亡人数的 9%。虽然临床稳定的 NB 患儿可以完全治愈,但高危疾病(HR-NB)患儿即使采用强化治疗策略也无法康复。需要开发新的有效的靶向治疗方法来对抗疾病进展,提高 HR-NB 患儿的长期生存率。
选择性回顾了 2017-2020 年与 NB 演变相关的最新研究,以识别新的有效的治疗靶点。将 HR-NB 的有前途的治疗靶点/策略分为(a)针对癌基因样和/或增强肿瘤抑制(TS)样长链非编码 RNA;(b)针对癌基因样 microRNAs(miRs)和/或模拟 TS-miRs;(c)免疫治疗靶点;(d)针对上皮-间充质转化和癌症干细胞;(e)新的和有益的联合方法;以及(f)在研药物和其他策略的再利用。
针对单一候选物或信号的药物不太可能对 HR-NB 的治愈有效。我们必须为功能靶点开发有效的药物输送系统,这可以整合并推进临床治疗。合适的是,越来越多的证据表明有希望的新的综合靶点具有积极的发展前景,开发高效药物,并改进 HR-NB 的治疗策略。