TOP2A gene copy gain predicts response of epithelial ovarian cancers to pegylated liposomal doxorubicin: TOP2A as marker of response to PLD in ovarian cancer.

摘要: Abstract Objective The treatment of platinum resistant/refractory epithelial ovarian cancer (EOC) is a challenge for oncologists. One the most utilized drugs in these patients pegylated liposomal doxorubicin (PLD). As PLD active only small subset and causes side effects, selection responsive an unmet need might be guided by status DNA topoisomerase II alpha (TOP2A) that poisoned drug. Methods From 176 cancers treated three institutions, we selected 38 with monotherapy as second/third line treatment. TOP2A gene copies were measured using Fluorescent In Situ Hybridization (FISH) expression evaluated immunohistochemistry. Patients' derived xenografts (PDXs) used to assess correlation between protein response PLD. Results Clinical data showed gain paralleled increased protein, was associated higher probability clinical benefit from Treatment PDXs demonstrated showing high percentage expressing cells underwent tumor shrinkage when Conclusions These show over-expression predict activity EOC.