Division of Oncology, University Children's Hospital of Zurich, Zurich 8032, Switzerland.
Molecules. 2013 Oct 10;18(10):12500-37. doi: 10.3390/molecules181012500.
Embryonal tumors include a heterogeneous group of highly malignant neoplasms that primarily affect infants and children and are characterized by a high rate of mortality and treatment-related morbidity, hence improved therapies are clearly needed. G-quadruplexes are special secondary structures adopted in guanine (G)-rich DNA sequences that are often present in biologically important regions, e.g. at the end of telomeres and in the regulatory regions of oncogenes such as MYC. Owing to the significant roles that both telomeres and MYC play in cancer cell biology, G-quadruplexes have been viewed as emerging therapeutic targets in oncology and as tools for novel anticancer drug design. Several compounds that target these structures have shown promising anticancer activity in tumor xenograft models and some of them have entered Phase II clinical trials. In this review we examine approaches to DNA targeted cancer therapy, summarize the recent developments of G-quadruplex ligands as anticancer drugs and speculate on the future direction of such structures as a potential novel therapeutic strategy for embryonal tumors of the nervous system.
胚胎性肿瘤包括一组高度恶性的肿瘤,主要影响婴儿和儿童,其死亡率和治疗相关发病率高,因此显然需要改进治疗方法。四链体是富含鸟嘌呤 (G) 的 DNA 序列中采用的特殊二级结构,这些序列通常存在于生物学上重要的区域,例如端粒的末端和原癌基因如 MYC 的调控区域。由于端粒和 MYC 在癌细胞生物学中都发挥着重要作用,因此四链体已被视为肿瘤学中新兴的治疗靶点,并被用作新型抗癌药物设计的工具。几种靶向这些结构的化合物在肿瘤异种移植模型中显示出有希望的抗癌活性,其中一些已进入 II 期临床试验。在这篇综述中,我们探讨了针对 DNA 的癌症治疗方法,总结了最近四链体配体作为抗癌药物的发展,并推测了这些结构作为神经系统胚胎性肿瘤潜在新治疗策略的未来方向。