Multiomic characterization and drug testing establish circulating tumor cells as an ex vivo tool for personalized medicine.
Multiomic characterization and drug testing establish circulating tumor cells as an ex vivo tool for personalized medicine.
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DOI：
10.1016/j.isci.2022.105081
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发表时间：
2022-10-21
期刊：
影响因子：
5.8
通讯作者：
Chang, Ying-Chih
中科院分区：
文献类型：
--
作者：
Chen, Jia-Yang;Chou, Hsu-Huan;Lim, Syer Choon;Huang, Yen-Jang;Lai, Kuan-Chen;Guo, Chin-Lin;Tung, Chien-Yi;Su, Chung-Tsai;Wang, Jocelyn;Liu, Edward;Han, Hsiao-Fen;Yeh, Po-Ying;Hu, Chun-Mei;Dunn, Alexander R.;Frank, Curtis W.;Wu, Yi-Chun;Yang, Muh-Hwa;Chang, Ying-Chih
将治疗与个体患者的肿瘤状态相匹配可以提高治疗效果并减少肿瘤复发。实体瘤来源的循环肿瘤细胞(CTCs)是一种很有前途的诊断分析对象。为了分析CTCs如何代表肿瘤状态，我们建立了CTCs的细胞系，从小鼠模型中获得原发和转移肿瘤，并提供了这些细胞的表型和多组学分析。CTCs和转移细胞，而不是原发肿瘤细胞，共享随机突变和相似的转录起始点的低甲基化水平。CTCs和转移性肿瘤细胞共享一种混合的上皮/间充质转录组状态，具有减少黏附和增强动员的特征。我们在一名转移性乳腺癌患者的肿瘤细胞上测试了抗癌药物。CTC反应反映了药物对转移性肿瘤的影响，而不是对原发肿瘤的影响。我们的多组学和临床抗癌药物反应结果显示，CTCs类似于转移性肿瘤，并建立了CTCs作为个性化药物的体外工具。直接比较来自小鼠模型的原代、CTC和转移细胞系多组学和表型数据表明循环细胞类似于转移细胞CTC和来自患者的转移肿瘤对抗癌药物的反应相似因此CTC可能用于筛选个体患者的药物反应精密药物；癌症；Omics；转录组
Matching the treatment to an individual patient’s tumor state can increase therapeutic efficacy and reduce tumor recurrence. Circulating tumor cells (CTCs) derived from solid tumors are promising subjects for theragnostic analysis. To analyze how CTCs represent tumor states, we established cell lines from CTCs, primary and metastatic tumors from a mouse model and provided phenotypic and multiomic analyses of these cells. CTCs and metastatic cells, but not primary tumor cells, shared stochastic mutations and similar hypomethylation levels at transcription start sites. CTCs and metastatic tumor cells shared a hybrid epithelial/mesenchymal transcriptome state with reduced adhesive and enhanced mobilization characteristics. We tested anti-cancer drugs on tumor cells from a metastatic breast cancer patient. CTC responses mirrored the impact of drugs on metastatic rather than primary tumors. Our multiomic and clinical anti-cancer drug response results reveal that CTCs resemble metastatic tumors and establish CTCs as an ex vivo tool for personalized medicine. Primary, CTC and metastatic cell lines from mouse models were directly compared Multiomic and phenotypic data indicate circulating cells resemble metastatic cells CTCs and metastasis tumors from a patient similarly respond to anti-cancer drugs CTCs are thus potentially useful for screening individual patient drug responses Precision medicine; Cancer; Omics; Transcriptomics
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影响因子：
21.3
作者：
通讯作者：
--
影响因子：
64.5
作者：
Cheung KJ;Gabrielson E;Werb Z;Ewald AJ
通讯作者：
Ewald AJ
影响因子：
28.4
作者：
Bidard, Francois-Clement;Jacot, William;Pierga, Jean-Yves
通讯作者：
Pierga, Jean-Yves
影响因子：
12.3
作者：
Akalin A;Kormaksson M;Li S;Garrett-Bakelman FE;Figueroa ME;Melnick A;Mason CE
通讯作者：
Mason CE
影响因子：
28.2
作者：
Drapkin BJ;George J;Christensen CL;Mino-Kenudson M;Dries R;Sundaresan T;Phat S;Myers DT;Zhong J;Igo P;Hazar-Rethinam MH;Licausi JA;Gomez-Caraballo M;Kem M;Jani KN;Azimi R;Abedpour N;Menon R;Lakis S;Heist RS;Büttner R;Haas S;Sequist LV;Shaw AT;Wong KK;Hata AN;Toner M;Maheswaran S;Haber DA;Peifer M;Dyson N;Thomas RK;Farago AF
通讯作者：
Farago AF