In vitro patient-derived 3D mesothelioma tumor organoids facilitate patient-centric therapeutic screening.
In vitro patient-derived 3D mesothelioma tumor organoids facilitate patient-centric therapeutic screening.
复制标题
DOI：
10.1038/s41598-018-21200-8
复制
发表时间：
2018-02-13
影响因子：
4.6
通讯作者：
Skardal A
中科院分区：
文献类型：
--
作者：
Mazzocchi AR;Rajan SAP;Votanopoulos KI;Hall AR;Skardal A
目前，通过精准医学将基因突变与化疗联系起来，解决了患者对抗癌药物反应的变异性。然而，精准医疗对治疗设计的实际好处尚不清楚。即使在鉴定出突变后，肿瘤学家通常也有几种药物选择，对于一些患者来说，没有明确的治疗方案。需要模型系统来帮助预测对化疗药物的个性化反应。我们直接从新鲜肿瘤活检组织中微工程化3D肿瘤类器官，以提供患者特异性模型，在开始治疗前可以进行治疗优化。我们展示了这个平台的初步实施，手术切除两个间皮瘤患者的肿瘤生物标本。首先，我们展示了在肿瘤芯片微流体装置内生物制造和维持可行的3D肿瘤构建体的能力。其次，我们证明了芯片上化疗筛选的结果模拟了在受试者本身中观察到的结果。最后，我们通过考虑精确医学遗传筛查的结果并确认非标准化合物3-deazaneplanocin A对已鉴定突变的有效性来证明突变特异性药物测试。这种患者源性肿瘤类器官策略适用于各种癌症，并可能提供一个框架，以改善精准医学肿瘤学的努力。
Variability in patient response to anti-cancer drugs is currently addressed by relating genetic mutations to chemotherapy through precision medicine. However, practical benefits of precision medicine to therapy design are less clear. Even after identification of mutations, oncologists are often left with several drug options, and for some patients there is no definitive treatment solution. There is a need for model systems to help predict personalized responses to chemotherapeutics. We have microengineered 3D tumor organoids directly from fresh tumor biopsies to provide patient-specific models with which treatment optimization can be performed before initiation of therapy. We demonstrate the initial implementation of this platform using tumor biospecimens surgically removed from two mesothelioma patients. First, we show the ability to biofabricate and maintain viable 3D tumor constructs within a tumor-on-a-chip microfluidic device. Second, we demonstrate that results of on-chip chemotherapy screening mimic those observed in subjects themselves. Finally, we demonstrate mutation-specific drug testing by considering the results of precision medicine genetic screening and confirming the effectiveness of the non-standard compound 3-deazaneplanocin A for an identified mutation. This patient-derived tumor organoid strategy is adaptable to a wide variety of cancers and may provide a framework with which to improve efforts in precision medicine oncology.
登录
查看更多内容
影响因子：
5.7
作者：
Ho, Won Jin;Pham, Edward A.;Wu, Benjamin M.
通讯作者：
Wu, Benjamin M.
影响因子：
64.5
作者：
Gao D;Vela I;Sboner A;Iaquinta PJ;Karthaus WR;Gopalan A;Dowling C;Wanjala JN;Undvall EA;Arora VK;Wongvipat J;Kossai M;Ramazanoglu S;Barboza LP;Di W;Cao Z;Zhang QF;Sirota I;Ran L;MacDonald TY;Beltran H;Mosquera JM;Touijer KA;Scardino PT;Laudone VP;Curtis KR;Rathkopf DE;Morris MJ;Danila DC;Slovin SF;Solomon SB;Eastham JA;Chi P;Carver B;Rubin MA;Scher HI;Clevers H;Sawyers CL;Chen Y
通讯作者：
Chen Y
影响因子：
19
作者：
Huh, Dongeun;Hamilton, Geraldine A.;Ingber, Donald E.
通讯作者：
Ingber, Donald E.
影响因子：
6.1
作者：
Cooksey, Gregory A.;Atencia, Javier
通讯作者：
Atencia, Javier
影响因子：
4.7
作者：
Drewitz, Maren;Helbling, Marianne;Kelm, Jens M.
通讯作者：
Kelm, Jens M.