Targeting the DNA damage response in cervical cancer

Hylke Wieringa

    Research output: ThesisThesis fully internal (DIV)

    1048 Downloads (Pure)


    Therapy improvement of cervical cancer by inhibition of DNA repair in tumor cells Treatment of locally-advanced cervical cancer consists of combined radio- and chemotherapy. Five-year survival of these patients is 66%. To further improve overall survival in cervical cancer patients, it is necessary to develop novel treatment modalities. It is suggested that inhibition of the DNA repair of tumor cells could be a way to sensitize cervical cancer cells for radio- and chemotherapy.

    Radio- and chemotherapy kill tumor cells (as well as normal cells) by induction of high amounts of DNA damage. This damage is not only repaired in normal cells, but also in tumor cells. Like in other cancer types, part of the signaling pathway involved in DNA repair in cervical cancer cells is defective. Consequently, cells increasingly depend on the remaining functional signaling pathways. The aim of this thesis was to investigate which of these remaining pathway components is the most promising candidate therapeutic target in cervical cancer cells to improve sensitization for radio- and chemotherapy.

    In this thesis, we show that inhibition of the ATR-Chk1 signaling pathway is the most efficient way to increase the effects of radio- and chemotherapy in cervical cancer cells. The results of this thesis may contribute to further improve the survival of cervical cancer patients.
    Original languageEnglish
    QualificationDoctor of Philosophy
    Awarding Institution
    • University of Groningen
    • van Vugt, Marcel, Supervisor
    • de Vries, Liesbeth, Supervisor
    • van der Zee, Ate, Supervisor
    Award date12-Apr-2017
    Place of Publication[Groningen]
    Print ISBNs978-90367-9656-9
    Electronic ISBNs978-90367-9657-6
    Publication statusPublished - 2017

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