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Verfasst von:Deng, Siyao [VerfasserIn]   i
 Vlatkovic, Tijana [VerfasserIn]   i
 Li, Moying [VerfasserIn]   i
 Zhan, Tianzuo [VerfasserIn]   i
 Veldwijk, Marlon Romano [VerfasserIn]   i
 Herskind, Carsten [VerfasserIn]   i
Titel:Targeting the DNA damage response and DNA repair pathways to enhance radiosensitivity in colorectal cancer
Verf.angabe:Siyao Deng, Tijana Vlatkovic, Moying Li, Tianzuo Zhan, Marlon R. Veldwijk and Carsten Herskind
E-Jahr:2022
Jahr:5 October 2022
Umfang:23 S.
Fussnoten:Gesehen am 21.12.2022
Titel Quelle:Enthalten in: Cancers
Ort Quelle:Basel : MDPI, 2009
Jahr Quelle:2022
Band/Heft Quelle:14(2022), 19, Artikel-ID 4874, Seite 1-23
ISSN Quelle:2072-6694
Abstract:Radiotherapy is an important component of current treatment options for colorectal cancer (CRC). It is either applied as neoadjuvant radiotherapy to improve local disease control in rectal cancers or for the treatment of localized metastatic lesions of CRC. DNA double-strand breaks (DSBs) are the major critical lesions contributing to ionizing radiation (IR)-induced cell death. However, CRC stem cells promote radioresistance and tumor cell survival through activating cell-cycle checkpoints to trigger the DNA damage response (DDR) and DNA repair after exposure to IR. A promising strategy to overcome radioresistance is to target the DDR and DNA repair pathways with drugs that inhibit activated cell-cycle checkpoint proteins, thereby improving the sensitivity of CRC cells to radiotherapy. In this review, we focus on the preclinical studies and advances in clinical trials of DNA-dependent protein kinase catalytic subunit (DNA-PKcs), ataxia telangiectasia mutated (ATM), ataxia telangiectasia and Rad3-related kinase (ATR), checkpoint kinase 1 (CHK1), checkpoint kinase 2 (CHK2), WEE1 and poly (ADP-ribose) polymerase 1 (PARP1) kinase inhibitors in CRC. Importantly, we also discuss the selective radiosensitization of CRC cells provided by synthetic lethality of these inhibitors and the potential for widening the therapeutic window by targeting the DDR and DNA repair pathways in combination with radiotherapy and immunotherapy.
DOI:doi:10.3390/cancers14194874
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext: https://doi.org/10.3390/cancers14194874
 Volltext: https://www.mdpi.com/2072-6694/14/19/4874
 DOI: https://doi.org/10.3390/cancers14194874
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:cell-cycle checkpoint inhibitors
 colorectal cancer
 DNA damage response
 DNA repair
 radiosensitivity
K10plus-PPN:1828230006
Verknüpfungen:→ Zeitschrift

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