Abstract
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.
Highlights
Embryonal tumors most commonly occur in the first few years of life and account for more than25% of childhood malignancies [1]
While much of the research has been focused on DNA G-quadruplexes, there has recently been a rapid emergence of interest in RNA G-quadruplexes, in the 5′-untranslated regions (UTRs) of mRNAs
In more than 85% of cancer cells, the telomere shortening is compensated by the telomerase enzyme that is especially up-regulated in cancer but not in somatic cells
Summary
Embryonal tumors most commonly occur in the first few years of life and account for more than. 25% of childhood malignancies [1] They include medulloblastoma (MB), neroblastoma (NB), soft tissue sarcomas, nephroblastoma (Wilm’s tumor), bone tumors, retinoblastoma, hepatoblastoma, germ-cell tumors and various other rare subtypes. Childhood MB is a cancer of the cerebellum, while NB arises in the sympathetic nervous system showing heterogeneous biological and clinical features. The development of novel therapeutic approaches based on identification of specific targets seems the most promising way forward to a better outcome for children with these unfavorable malignant tumors [6,7]. This review examines approaches to DNA targeted therapy, describes recent developments of G-quadruplex ligands as anticancer drugs and discusses their potential as therapeutic targets, for embryonal tumors of the nervous system
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