Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	Targeting ATR Pathway in Solid Tumors: Evidence of Improving Therapeutic Outcomes
Δημιουργός/Συγγραφέας:	Mavroeidi, Dimitra Georganta, Anastasia Panagiotou, Emmanouil Syrigos, Konstantinos [EL] Σουλιώτης, Βασίλης Λ.[EN] Souliotis, Vassilis L.
Ημερομηνία:	2024-02-27
Γλώσσα:	Αγγλικά
ISSN:	1422-0067
DOI:	10.3390/ijms25052767
Άλλο:	38474014
Περίληψη:	The DNA damage response (DDR) system is a complicated network of signaling pathways that detects and repairs DNA damage or induces apoptosis. Critical regulators of the DDR network include the DNA damage kinases ataxia telangiectasia mutated Rad3-related kinase (ATR) and ataxia-telangiectasia mutated (ATM). The ATR pathway coordinates processes such as replication stress response, stabilization of replication forks, cell cycle arrest, and DNA repair. ATR inhibition disrupts these functions, causing a reduction of DNA repair, accumulation of DNA damage, replication fork collapse, inappropriate mitotic entry, and mitotic catastrophe. Recent data have shown that the inhibition of ATR can lead to synthetic lethality in ATM-deficient malignancies. In addition, ATR inhibition plays a significant role in the activation of the immune system by increasing the tumor mutational burden and neoantigen load as well as by triggering the accumulation of cytosolic DNA and subsequently inducing the cGAS-STING pathway and the type I IFN response. Taken together, we review stimulating data showing that ATR kinase inhibition can alter the DDR network, the immune system, and their interplay and, therefore, potentially provide a novel strategy to improve the efficacy of antitumor therapy, using ATR inhibitors as monotherapy or in combination with genotoxic drugs and/or immunomodulators.
Τίτλος πηγής δημοσίευσης:	International journal of molecular sciences
Τόμος/Κεφάλαιο:	25
Τεύχος:	5
Θεματική Κατηγορία:	[EL] Νεοπλάσματα. Όγκοι. Ογκολογία (περ. Καρκίνος, κακινογόνες ουσίες)[EN] Neoplasms. Tumors. Oncology (Incl.cancer, carcinogens) [EL] Μοριακή Βιολογία[EN] Molecular Biology [EL] Θεραπευτική. Φαρμακολογία[EN] Therapeutics.Pharmacology [EL] Ανοσολογία[EN] Immunology
Λέξεις-Κλειδιά:	ATR ATR inhibitor ATR-ATM interplay DNA damage response ceralasertib (AZD6738) immune system synthetic lethality
Κάτοχος πνευματικών δικαιωμάτων:	© 2024 by the authors. Licensee MDPI, Basel, Switzerland.
Όροι και προϋποθέσεις δικαιωμάτων:	This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).
Ηλεκτρονική διεύθυνση στον εκδότη (link):	https://doi.org/10.3390/ijms25052767
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο