Modulating the DNA Damage Response to Improve Treatment Response in Cervical Cancer.
Cervical cancer is the fourth most common cause of cancer-related death in women worldwide and new therapeutic approaches are needed to improve clinical outcomes for this group of patients. Current treatment protocols for locally advanced and metastatic disease consist of ionising radiation and chemotherapy. Chemoradiation induces cytotoxic levels of DNA double-strand breaks, which activates programmed cell death via the DNA damage response (DDR). Cervical cancers are unique given an almost exclusive association with human papillomavirus (HPV) infection; a potent manipulator of the DDR, with the potential to alter tumour sensitivity to DNA-damaging agents and influence treatment response. This review highlights the wide range of therapeutic strategies in development that have the potential to modulate DDR and sensitise cervical tumours to DNA-damaging agents in the context of HPV oncogenesis.
Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool, Liverpool, UK; Clatterbridge Cancer Centre, Wirral, UK. Electronic address: lcossar@liv.ac.uk.
L H
LH
Cossar
Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
A G
AG
Schache
Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
J M
JM
Risk
Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool, Liverpool, UK; Clatterbridge Cancer Centre, Wirral, UK.
J J
JJ
Sacco
Department of Biochemistry, Institute of Integrative Biology, University of Liverpool, Liverpool, UK.
N J
NJ
Jones
Clatterbridge Cancer Centre, Wirral, UK.
R
R
Lord
D004249:DNA Damage / Q000235:genetics*; D005260:Female; D006801:Humans; D030361:Papillomavirus Infections / Q000150:complications*; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology
Cervical cancer; DNA damage response; HPV