G-quadruplexes: a promising target for cancer therapy

DNA and RNA can fold into a variety of alternative conformations. In recent years, a particular nucleic acid structure was discussed to play a role in malignant transformation and cancer development. This structure is called a G-quadruplex (G4). G4 structure formation can drive genome instability by...

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Autores principales: Kosiol, Nils, Juranek, Stefan, Brossart, Peter, Heine, Annkristin, Paeschke, Katrin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905668/
https://www.ncbi.nlm.nih.gov/pubmed/33632214
http://dx.doi.org/10.1186/s12943-021-01328-4
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author Kosiol, Nils
Juranek, Stefan
Brossart, Peter
Heine, Annkristin
Paeschke, Katrin
author_facet Kosiol, Nils
Juranek, Stefan
Brossart, Peter
Heine, Annkristin
Paeschke, Katrin
author_sort Kosiol, Nils
collection PubMed
description DNA and RNA can fold into a variety of alternative conformations. In recent years, a particular nucleic acid structure was discussed to play a role in malignant transformation and cancer development. This structure is called a G-quadruplex (G4). G4 structure formation can drive genome instability by creating mutations, deletions and stimulating recombination events. The importance of G4 structures in the characterization of malignant cells was currently demonstrated in breast cancer samples. In this analysis a correlation between G4 structure formation and an increased intratumor heterogeneity was identified. This suggests that G4 structures might allow breast cancer stratification and supports the identification of new personalized treatment options. Because of the stability of G4 structures and their presence within most human oncogenic promoters and at telomeres, G4 structures are currently tested as a therapeutic target to downregulate transcription or to block telomere elongation in cancer cells. To date, different chemical molecules (G4 ligands) have been developed that aim to target G4 structures. In this review we discuss and compare G4 function and relevance for therapeutic approaches and their impact on cancer development for three cancer entities, which differ significantly in their amount and type of mutations: pancreatic cancer, leukemia and malignant melanoma. G4 structures might present a promising new strategy to individually target tumor cells and could support personalized treatment approaches in the future.
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spelling pubmed-79056682021-02-25 G-quadruplexes: a promising target for cancer therapy Kosiol, Nils Juranek, Stefan Brossart, Peter Heine, Annkristin Paeschke, Katrin Mol Cancer Review DNA and RNA can fold into a variety of alternative conformations. In recent years, a particular nucleic acid structure was discussed to play a role in malignant transformation and cancer development. This structure is called a G-quadruplex (G4). G4 structure formation can drive genome instability by creating mutations, deletions and stimulating recombination events. The importance of G4 structures in the characterization of malignant cells was currently demonstrated in breast cancer samples. In this analysis a correlation between G4 structure formation and an increased intratumor heterogeneity was identified. This suggests that G4 structures might allow breast cancer stratification and supports the identification of new personalized treatment options. Because of the stability of G4 structures and their presence within most human oncogenic promoters and at telomeres, G4 structures are currently tested as a therapeutic target to downregulate transcription or to block telomere elongation in cancer cells. To date, different chemical molecules (G4 ligands) have been developed that aim to target G4 structures. In this review we discuss and compare G4 function and relevance for therapeutic approaches and their impact on cancer development for three cancer entities, which differ significantly in their amount and type of mutations: pancreatic cancer, leukemia and malignant melanoma. G4 structures might present a promising new strategy to individually target tumor cells and could support personalized treatment approaches in the future. BioMed Central 2021-02-25 /pmc/articles/PMC7905668/ /pubmed/33632214 http://dx.doi.org/10.1186/s12943-021-01328-4 Text en © The Author(s) 2021 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Review
Kosiol, Nils
Juranek, Stefan
Brossart, Peter
Heine, Annkristin
Paeschke, Katrin
G-quadruplexes: a promising target for cancer therapy
title G-quadruplexes: a promising target for cancer therapy
title_full G-quadruplexes: a promising target for cancer therapy
title_fullStr G-quadruplexes: a promising target for cancer therapy
title_full_unstemmed G-quadruplexes: a promising target for cancer therapy
title_short G-quadruplexes: a promising target for cancer therapy
title_sort g-quadruplexes: a promising target for cancer therapy
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905668/
https://www.ncbi.nlm.nih.gov/pubmed/33632214
http://dx.doi.org/10.1186/s12943-021-01328-4
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