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Cancer Treat Rev. 2016 Jan;42:30-40. doi: 10.1016/j.ctrv.2015.11.008. Epub 2015 Nov 24.

Breaking the DNA damage response to improve cervical cancer treatment.

Author information

1
Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Department of Gynecologic Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
2
Department of Gynecologic Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
3
Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
4
Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. Electronic address: m.vugt@umcg.nl.

Abstract

Every year, cervical cancer affects ∼500,000 women worldwide, and ∼275,000 patients die of this disease. The addition of platin-based chemotherapy to primary radiotherapy has increased 5-year survival of advanced-stage cervical cancer patients, which is, however, still only 66%. One of the factors thought to contribute to treatment failure is the ability of tumor cells to repair chemoradiotherapy-induced DNA damage. Therefore, sensitization of tumor cells for chemoradiotherapy via inhibition of the DNA damage response (DDR) as a novel strategy to improve therapy effect, is currently studied pre-clinically as well as in the clinic. Almost invariably, cervical carcinogenesis involves infection with the human papillomavirus (HPV), which inactivates part of the DNA damage response. This HPV-mediated partial inactivation of the DDR presents therapeutic targeting of the residual DDR as an interesting approach to achieve chemoradio-sensitization for cervical cancer. How the DDR can be most efficiently targeted, however, remains unclear. The fact that cisplatin and radiotherapy activate multiple signaling axes within the DDR further complicates a rational choice of therapeutic targets within the DDR. In this review, we provide an overview of the current preclinical and clinical knowledge about targeting the DDR in cervical cancer.

KEYWORDS:

Cervical cancer; Cisplatin; DDR-inhibitors; DNA damage response; Radiotherapy

PMID:
26643553
DOI:
10.1016/j.ctrv.2015.11.008
[Indexed for MEDLINE]

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