Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=26964031
&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215
Triapine potentiates platinum-based combination therapy by disruption of
homologous recombination repair
#MMPMID26964031
Ratner ES
; Zhu YL
; Penketh PG
; Berenblum J
; Whicker ME
; Huang PH
; Lee Y
; Ishiguro K
; Zhu R
; Sartorelli AC
; Lin ZP
Br J Cancer
2016[Mar]; 114
(7
): 777-86
PMID26964031
show ga
BACKGROUND: Platinum resistance may be attributable to inherent or acquired
proficiency in homologous recombination repair (HRR) in epithelial ovarian cancer
(EOC). The objective of this study was to evaluate the efficacy of the small
molecule inhibitor triapine to disrupt HRR and sensitise BRCA wild-type EOC cells
to platinum-based combination therapy in vitro and in vivo. METHODS: The
sensitivity of BRCA wild-type cancer cells to olaparib, cisplatin, carboplatin,
doxorubicin, or etoposide in combination with triapine was evaluated by
clonogenic survival assays. The effects of triapine on HRR activity in cells were
measured with a DR-GFP reporter assay. The ability of triapine to enhance the
effects of the carboplatin-doxil combination on EOC tumour growth delay was
determined using a xenograft tumour mouse model. RESULTS: Platinum resistance is
associated with wild-type BRCA status. Triapine inhibits HRR activity and
enhances the sensitivity of BRCA wild-type cancer cells to cisplatin, olaparib,
and doxorubicin. However, sequential combination of triapine and cisplatin is
necessary to achieve synergism. Moreover, triapine potentiates platinum-based
combination therapy against BRCA wild-type EOC cells and produces significant
delay of EOC tumour growth. CONCLUSIONS: Triapine promises to augment the
clinical efficacy of platinum-based combination regimens for treatment of
platinum-resistant EOC with wild-type BRCA and proficient HRR activity.
free
free
free
