PARP-1 activity (PAR) determines the sensitivity of cervical cancer to olaparib
Gynecologic Oncology Aug 23, 2019
Bianchi A, Lopez S, Altwerger G, et al. - Given poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors (PARPi) are promising in treating ovarian cancer, researchers focused on the preclinical in vitro and in vivo activity of olaparib against multiple primary whole exome sequenced cervical cancer (CC) cells lines and xenografts. They evaluated olaparib cell-cycle, apoptosis, homologous-recombination-deficiency, PARP trapping and cytotoxicity activity against 9 primary CC cell lines in vitro. Using Western blot assays, they assessed PARP and PAR expression. Against CC xenografts, the antitumor activity of olaparib was tested in vivo. Findings revealed the high responsiveness of a subset of CC primary cell lines to olaparib treatment in vitro and in vivo. There was a correlation between high level of PARylation and olaparib preclinical activity. Furthermore, high level of PARylation could have utility as a biomarker for the detection of CC patients benefitting the most from PARPi.
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