Carboplatin response in preclinical models for ovarian cancer: comparison of 2D monolayers, spheroids, ex vivo tumors and in vivo models.
Carboplatin response in preclinical models for ovarian cancer: comparison of 2D monolayers, spheroids, ex vivo tumors and in vivo models.
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DOI：
10.1038/s41598-021-97434-w
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发表时间：
2021-09-14
影响因子：
4.6
通讯作者：
Mes-Masson AM
中科院分区：
文献类型：
--
作者：
Brodeur MN;Simeone K;Leclerc-Deslauniers K;Fleury H;Carmona E;Provencher DM;Mes-Masson AM
上皮性卵巢癌（EOC）是最致命的妇科癌症。开发有效疗法的关键挑战之一是药物发现管道中使用的临床前模型的翻译不佳。这使得药物损耗率和成本处于不可接受的高水平。先前的工作强调了目前体外和体内模型之间治疗反应的差异。为了解决这个问题，我们进行了一项比较研究，以区分卡铂化疗在四种不同模型系统中的反应，包括2D单层、3D球体、3D离体肿瘤和小鼠异种移植模型。我们使用了六种不同化学敏感性的先前表征的EOC细胞系，并对每种模型进行了活力测定。小鼠模型的体内结果在3/6细胞系中与2D反应相关，在4/6和5/5细胞系中与3D球体和离体模型相关。我们的研究结果强调了不同模型治疗反应的可变性，并证明在3D离体模型中培养的EOC细胞系的卡铂反应与体内反应最相关。这些结果强调了一种更可行、更可靠、更具成本效益的临床前模型，具有最高的转化潜力，可用于EOC的药物筛选和预测研究。
Epithelial ovarian cancer (EOC) is the most lethal gynecological cancer. Among the key challenges in developing effective therapeutics is the poor translation of preclinical models used in the drug discovery pipeline. This leaves drug attrition rates and costs at an unacceptably high level. Previous work has highlighted the discrepancies in therapeutic response between current in vitro and in vivo models. To address this, we conducted a comparison study to differentiate the carboplatin chemotherapy response across four different model systems including 2D monolayers, 3D spheroids, 3D ex vivo tumors and mouse xenograft models. We used six previously characterized EOC cell lines of varying chemosensitivity and performed viability assays for each model. In vivo results from the mouse model correlated with 2D response in 3/6 cell lines while they correlated with 3D spheroids and the ex vivo model in 4/6 and 5/5 cell lines, respectively. Our results emphasize the variability in therapeutic response across models and demonstrate that the carboplatin response in EOC cell lines cultured in a 3D ex vivo model correlates best with the in vivo response. These results highlight a more feasible, reliable, and cost-effective preclinical model with the highest translational potential for drug screening and prediction studies in EOC.
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影响因子：
4.6
作者：
Davies EJ;Dong M;Gutekunst M;Närhi K;van Zoggel HJ;Blom S;Nagaraj A;Metsalu T;Oswald E;Erkens-Schulze S;Delgado San Martin JA;Turkki R;Wedge SR;af Hällström TM;Schueler J;van Weerden WM;Verschuren EW;Barry ST;van der Kuip H;Hickman JA
通讯作者：
Hickman JA
影响因子：
3.2
作者：
Das, Tamal;Meunier, Liliane;Mes-Masson, Anne-Marie
通讯作者：
Mes-Masson, Anne-Marie
影响因子：
5.7
作者：
Aihara A;Abe N;Saruhashi K;Kanaki T;Nishino T
通讯作者：
Nishino T
影响因子：
16.6
作者：
Majumder, Biswanath;Baraneedharan, Ulaganathan;Thiyagarajan, Saravanan;Radhakrishnan, Padhma;Narasimhan, Harikrishna;Dhandapani, Muthu;Brijwani, Nilesh;Pinto, Dency D.;Prasath, Arun;Shanthappa, Basavaraja U.;Thayakumar, Allen;Surendran, Rajagopalan;Babu, Govind K.;Shenoy, Ashok M.;Kuriakose, Moni A.;Bergthold, Guillaume;Horowitz, Peleg;Loda, Massimo;Beroukhim, Rameen;Agarwal, Shivani;Sengupta, Shiladitya;Sundaram, Mallikarjun;Majumder, Pradip K.
通讯作者：
Majumder, Pradip K.
影响因子：
11.2
作者：
Hirst J;Pathak HB;Hyter S;Pessetto ZY;Ly T;Graw S;Koestler DC;Krieg AJ;Roby KF;Godwin AK
通讯作者：
Godwin AK