Telomere maintenance in interplay with DNA repair in pathogenesis and treatment of colorectal cancer

0539305 - ÚEM 2021 RIV GB eng J - Článek v odborném periodiku
Tomášová, Kristýna - Kroupa, Michal - Försti, A. - Vodička, Pavel - Vodičková, Ludmila
Telomere maintenance in interplay with DNA repair in pathogenesis and treatment of colorectal cancer.
Mutagenesis. Roč. 35, č. 3 (2020), s. 261-271. ISSN 0267-8357. E-ISSN 1464-3804
Grant CEP: GA MZd(CZ) NV18-03-00199; GA MZd(CZ) NV15-27580A; GA ČR(CZ) GA18-09709S
Institucionální podpora: RVO:68378041
Klíčová slova: nucleotide excision-repair * double-strand breaks * quadruplex DNA
Obor OECD: Pharmacology and pharmacy
Impakt faktor: 3.000, rok: 2020
Způsob publikování: Omezený přístup
https://academic.oup.com/mutage/article-abstract/35/3/261/5743334?redirectedFrom=fulltext

Colorectal cancer (CRC) continues to be one of the leading malignancies and causes of tumour-related deaths worldwide. Both impaired DNA repair mechanisms and disrupted telomere length homeostasis represent key culprits in CRC initiation, progression and prognosis. Mechanistically, altered DNA repair results in the accumulation of mutations in the genome and, ultimately, in genomic instability. DNA repair also determines the response to chemotherapeutics in CRC treatment, suggesting its utilisation in the prediction of therapy response and individual approach to patients. Telomere attrition resulting in replicative senescence, simultaneously bypassing cell cycle checkpoints, is a hallmark of malignant transformation of the cell. Telomerase is almost ubiquitous in advanced solid cancers, including CRC, and its expression is fundamental to cell immortalisation. Therefore, there is a persistent effort to develop therapeutics, which are telomerase-specific and gentle to non-malignant tissues. However, in practice, we are still at the level of clinical trials. The current state of knowledge and the route, which the research takes, gives us a positive perspective that the problem of molecular models of telomerase activation and telomere length stabilisation will finally be solved. We summarise the current literature herein, by pointing out the crosstalk between proteins involved in DNA repair and telomere length homeostasis in relation to CRC.
Trvalý link: http://hdl.handle.net/11104/0316996