期刊
GYNECOLOGIC ONCOLOGY
卷 138, 期 3, 页码 627-633出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ygyno.2015.06.025
关键词
Topoisomerases; Predictive biomarkers; Doxorubicin; PDX (patient derived xenografts)
资金
- Ricerca Finanziata dall'Universita di Torino
- CUP [D55E12002380005]
- IG Grant of the Italian Association of Cancer Research (AIRC) [13050]
- CARIPLO Foundation
Objective. The treatment of platinum resistant/refractory epithelial ovarian cancer (EOC) is a challenge for oncologists. One of the most utilized drugs in these patients is pegylated liposomal doxorubicin (PLO). As PLD is active only in a small subset of patients and causes side effects, selection of responsive patients is an unmet need and might be guided by the status of the DNA topoisomerase II alpha (TOP2A) that is poisoned by the drug. Methods. From 176 ovarian cancers treated in three institutions, we selected 38 patients treated with PLO monotherapy as second/third line of treatment. TOP2A gene copies were measured using Fluorescent In Situ Hybridization (FISH) and expression evaluated using immunohistochemistry. Patients' derived xenografts (PDXs) of ovarian cancers were used to assess the correlation between TOP2A protein expression and response to PLO. Results. Clinical data showed that TOP2A gene gain that is paralleled by increased expression of the protein, was associated with a higher probability of clinical benefit from PLD. Treatment of PDXs demonstrated that only xenografts showing a high percentage of TOP2A expressing cells underwent tumor shrinkage when treated with PLO. Conclusions. These data show that TOP2A gene gain and protein over-expression might predict activity of PLO in platinum resistant/refractory EOC. (C) 2015 Elsevier Inc. All rights reserved.
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