Combination of paclitaxel, bevacizumab and MEK162 in second line treatment in platinum-relapsing patient derived ovarian cancer xenografts

Molecular Cancer

Letter to the Editor

Giovanna Damia¹  Massimo Broggini¹  Francesca Ricci¹  Federica Guffanti¹ 

[1] Laboratory of Molecular Pharmacology, IRCCS - Istituto di Ricerche Farmacologiche “Mario Negri”, via Giuseppe La Masa 19, 20156, Milan, Italy;

关键词: Ovarian cancer;    Second line;    Patients derived xenografts;    Cisplatin;    Drug resistance;    Combination chemotherapy;   

DOI  :  10.1186/s12943-017-0662-3

 received in 2016-12-20, accepted in 2017-05-15,  发布年份 2017

来源: Springer

【 摘 要 】

Advanced ovarian cancer is very responsive to first line platinum therapy, however almost invariably it relapses with a resistant disease. We have reported that patient derived ovarian xenografts (PDXs), independently from the degree of the initial response to cisplatin (DDP), show a significantly lower response to a second DDP cycle. We here report the effect of new combination regimens containing a MEK inhibitor (MEK), bevacizumab (BEV) and paclitaxel (PTX) as second line therapy in platinum-relapsing PDXs.We selected three DDP-relapsing PDX models based on the presence of activation of the RAS/RAF/MEK/ERK axis, mutated p53, lack of PTEN expression and activation of the PI3K pathway. In all the selected xenograft models, the antitumor efficacy of the doublets can be summarized as PTX/BEV > BEV/MEK > PTX/MEK and the antitumor activity of the triple combination was higher than any double combination. All the different combinations were well tolerated. The present data corroborate the activity of bevacizumab in combination with chemotherapy for the treatment of relapsing ovarian tumors and suggest that the addition of another targeted agents (MEK inhibitor) can further increase the antitumor activity without any increase in toxicity. PDX models represent a useful model to test second line therapy after failure of DDP first line.

【 授权许可】

CC BY   
© The Author(s). 2017