G-Quadruplexes as Potential Therapeutic Targets for Embryonal Tumors

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.

Targeting DNA mismatches with rhodium metalloinsertors

“…Since the discoveries of these therapeutics, the versatility of DNA as a target has been significantly expanded. Therapeutics have been seen to bind covalently to DNA (alkylating agents, platinum drugs), non-covalently interact with DNA (actinomycin D, mitomycins, polyamides), to interfere with protein-DNA complexes (doxorubicin, etoposide), and even target DNA secondary structures such as G-quadruplexes (intrafloxin, in phase II clinical trials) [5–8]. These complexes and more DNA-targeting chemotherapeutics have been reviewed recently [5,9].…”

Targeting G-Quadruplex DNA Structures by EMICORON Has a Strong Antitumor Efficacy against Advanced Models of Human Colon Cancer

“…G-quadruplex (G4) ligands are small molecules able to bind to and stabilize G4 structures widely described at the telomeric ends of chromosomes (1)(2)(3)(4)(5)(6). Interest in the more general therapeutic significance of G4 has expanded during the past decade including G4 structures in the promoters of a wide range of genes important in cell signaling, recognized as hallmarks of cancer.…”

Design and Synthesis of a Berberine Dimer: A Fluorescent Ligand with High Affinity towards G‐Quadruplexes

“…Telomeric G4 also inhibit telomerase, which is a reverse transcriptase that elongates telomeres in a wide variety of cancer cells, resulting in almost infinite cellular proliferation. Accordingly, telomeric G4 represents a highly promising research target for the development of anticancer drugs 6…”