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Poly(ADP-Ribose) Polymerase in Cervical Cancer Pathogenesis: Mechanism and Potential Role for PARP Inhibitors
  1. Ioannis C. Kotsopoulos, MD, PhD,
  2. Ali Kucukmetin, MD, MRCOG,
  3. Asima Mukhopadhyay, MD, PhD, MRCOG,
  4. John Lunec, PhD, MRCR, FRCPath and
  5. Nicola J. Curtin, PhD
  1. * Northern Gynaecological Oncology Centre, Queen Elizabeth Hospital, Gateshead; and
  2. Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, United Kingdom.
  1. Address correspondence and reprint requests to Ioannis C. Kotsopoulos, MD, PhD, Northern Gynaecological Oncology Centre, Queen Elizabeth Hospital, Sheriff Hill, Gateshead, Tyne and Wear, NE9 6SX; Northern Institute for Cancer Research, Paul O’Gorman Bldg, Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4HH, United Kingdom. E-mail: i.kotsopoulos1{at}newcastle.ac.uk.

Abstract

Abstract Treatment options for disease recurrence of women treated for locally advanced and advanced cervical cancer are very limited—largely palliative chemotherapy. The low efficacy of the currently available drugs raises the need for new targeted agents. Poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors (PARPi) have emerged as a promising class of chemotherapeutic agents in cancers associated with defects in DNA repair. Their therapeutic potential in cervical cancer is currently being evaluated in 3 ongoing clinical trials. Here we review the available information regarding all the aspects of PARP in cervical intraepithelial neoplasia and invasive cervical cancer, from expression and the mechanism of action to the role of the polymorphisms in the pathogenesis of the disease, as well as the potential of the inhibitors. We finally propose a new unifying theory regarding the role of PARPs in the development of cervical carcinomas.

  • Poly(ADP-ribose) polymerase
  • PARP
  • Cervical cancer
  • CIN
  • Carcinogenesis

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Footnotes

  • The authors declare no conflicts of interest.

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