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Inhibition of replication origins and ATR synergistically activates the innate immune system in cancer cells

In cancer cells, maintaining an adequate number of active replication origins is crucial for successful DNA replication. Our study explores a novel strategy to enhance the effectiveness of ATR inhibitors in ovarian cancer treatment by targeting replication origins. We demonstrate that inhibiting rep...

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Autori principali: Doberstein, Kai (Autore) , Panther, Johannes (Autore) , Berlit, Sebastian (Autore) , Tuschy, Benjamin (Autore) , Sütterlin, Marc (Autore) , Marmé, Frederik (Autore)
Natura: Article (Journal)
Lingua:inglese
Pubblicazione: March 2026
In: Heliyon
Year: 2026, Volume: 12, Fascicolo: 3, Pages: 1-18
ISSN:2405-8440
DOI:10.1016/j.heliyon.2026.e44610
Accesso online:Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.heliyon.2026.e44610
Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S2405844026001155
Testo
Note sull'autore:Kai Doberstein, Johannes Panther, Sebastian Berlit, Benjamin Tuschy, Marc Sütterlin, Frederik Marmé
Descrizione
Riassunto:In cancer cells, maintaining an adequate number of active replication origins is crucial for successful DNA replication. Our study explores a novel strategy to enhance the effectiveness of ATR inhibitors in ovarian cancer treatment by targeting replication origins. We demonstrate that inhibiting replication origin activation and reducing their number sensitizes ovarian cancer cells to ATR inhibition, leading to increased genomic instability. This combinatorial approach activates the innate immune system through the cGAS-STING pathway, potentially enhancing the immune response within tumors. Importantly, this effect is not observed in normal cells, highlighting its cancer-specific potential. Our findings offer a promising avenue for improving ATR inhibitor therapy and leveraging innate immunity in cancer treatment.
Descrizione del documento:Online verfügbar: 18. Februar 2026, Artikelversion: 18. Februar 2026
Gesehen am 13.07.2026
Descrizione fisica:Online Resource
ISSN:2405-8440
DOI:10.1016/j.heliyon.2026.e44610

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