Patient-derived organoids model treatment response of metastatic gastrointestinal cancers.
Patient-derived organoids model treatment response of metastatic gastrointestinal cancers.
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DOI：
10.1126/science.aao2774
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发表时间：
2018-02-23
期刊：
影响因子：
--
通讯作者：
Valeri N
中科院分区：
文献类型：
--
作者：
Vlachogiannis G;Hedayat S;Vatsiou A;Jamin Y;Fernández-Mateos J;Khan K;Lampis A;Eason K;Huntingford I;Burke R;Rata M;Koh DM;Tunariu N;Collins D;Hulkki-Wilson S;Ragulan C;Spiteri I;Moorcraft SY;Chau I;Rao S;Watkins D;Fotiadis N;Bali M;Darvish-Damavandi M;Lote H;Eltahir Z;Smyth EC;Begum R;Clarke PA;Hahne JC;Dowsett M;de Bono J;Workman P;Sadanandam A;Fassan M;Sansom OJ;Eccles S;Starling N;Braconi C;Sottoriva A;Robinson SP;Cunningham D;Valeri N
患者源性类器官（PDOs）最近作为强大的临床前模型出现，然而，它们预测患者临床结果的潜力仍不清楚。我们报告了一个从I/II期临床试验中招募的转移性、重度预处理的结直肠癌和胃食管癌患者的pdo活生物库。PDOs的表型和基因型分析显示与原始患者肿瘤高度相似。肿瘤类器官的分子谱分析与药物筛选结果相匹配，表明PDOs可以补充现有的方法来定义癌症脆弱性和改善治疗反应。我们比较了体外类器官对抗癌药物的反应，以及基于pdo的原位小鼠肿瘤异种移植模型在临床试验中的反应。我们的数据表明，pdo可以在临床中概括患者的反应，并且有可能在个性化医疗计划中实施。
Patient-derived organoids (PDOs) have recently emerged as robust pre-clinical models, however, their potential to predict patient clinical outcomes remain unclear. We report a living biobank of PDOs from metastatic, heavily-pretreated colorectal and gastroesophageal cancer patients recruited in phase I/II clinical trials. Phenotypic and genotypic profiling of PDOs showed a high-degree of similarity to the original patient tumor. Molecular profiling of tumor organoids was matched to drug screening results, suggesting PDOs could complement existing approaches in defining cancer vulnerabilities and improving treatment responses. We compared ex vivo organoid responses to anticancer agents, and PDO-based orthotopic mouse tumor xenograft models to the response of the patient in clinical trials. Our data suggest that PDOs can recapitulate patient responses in the clinic, and have the potential to be implemented in personalized medicine programs.
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影响因子：
28.2
作者：
Pauli C;Hopkins BD;Prandi D;Shaw R;Fedrizzi T;Sboner A;Sailer V;Augello M;Puca L;Rosati R;McNary TJ;Churakova Y;Cheung C;Triscott J;Pisapia D;Rao R;Mosquera JM;Robinson B;Faltas BM;Emerling BE;Gadi VK;Bernard B;Elemento O;Beltran H;Demichelis F;Kemp CJ;Grandori C;Cantley LC;Rubin MA
通讯作者：
Rubin MA
DOI：
10.1056/nejmoa1502309
发表时间：
2015-08-20
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hyman DM;Puzanov I;Subbiah V;Faris JE;Chau I;Blay JY;Wolf J;Raje NS;Diamond EL;Hollebecque A;Gervais R;Elez-Fernandez ME;Italiano A;Hofheinz RD;Hidalgo M;Chan E;Schuler M;Lasserre SF;Makrutzki M;Sirzen F;Veronese ML;Tabernero J;Baselga J
通讯作者：
Baselga J
影响因子：
64.5
作者：
van de Wetering M;Francies HE;Francis JM;Bounova G;Iorio F;Pronk A;van Houdt W;van Gorp J;Taylor-Weiner A;Kester L;McLaren-Douglas A;Blokker J;Jaksani S;Bartfeld S;Volckman R;van Sluis P;Li VS;Seepo S;Sekhar Pedamallu C;Cibulskis K;Carter SL;McKenna A;Lawrence MS;Lichtenstein L;Stewart C;Koster J;Versteeg R;van Oudenaarden A;Saez-Rodriguez J;Vries RG;Getz G;Wessels L;Stratton MR;McDermott U;Meyerson M;Garnett MJ;Clevers H
通讯作者：
Clevers H
影响因子：
50.5
作者：
Smyth, E. C.;Verheij, M.;Arnold, D.
通讯作者：
Arnold, D.
影响因子：
78.8
作者：
Clohessy, John G.;Pandolfi, Pier Paolo
通讯作者：
Pandolfi, Pier Paolo