Tumor-on-a-chip platform to investigate progression and drug sensitivity in cell lines and patient-derived organoids.
Tumor-on-a-chip platform to investigate progression and drug sensitivity in cell lines and patient-derived organoids.
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DOI：
10.1039/c8lc00596f
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发表时间：
2018-12-07
期刊：
影响因子：
6.1
通讯作者：
George SC
中科院分区：
文献类型：
--
作者：
Shirure VS;Bi Y;Curtis MB;Lezia A;Goedegebuure MM;Goedegebuure SP;Aft R;Fields RC;George SC
大多数癌症治疗策略以肿瘤细胞增殖、血管生成、迁移和内渗为目标，试图限制肿瘤的生长和转移。一个评估肿瘤进展和药物敏感性的体外平台可以为提高我们对肿瘤转移的理解和精准医疗提供途径。我们提出了一个微流控平台，模拟肿瘤微环境中毛细血管动脉端附近的生物物质运输。中心特征是在将肿瘤细胞或患者来源的肿瘤类器官装入相邻的隔室之前创建的静止灌注的3D微血管网络。然后，营养物质和/或药物通过血管网络向肿瘤进行生理输送。我们展示了肿瘤细胞系和患者来源的乳腺癌类器官的培养、生长和治疗。该平台提供了同时和动态观察肿瘤进展的标志性特征的机会，包括细胞增殖、血管生成、细胞迁移和肿瘤细胞内渗。此外，原发性乳腺肿瘤类器官在该装置中可存活数周，并诱导血管新生。最后，我们通过分析对化疗和抗血管生成治疗的反应来证明我们的平台在药物发现和个性化医疗方面的可行性。只有在临床相关的时间范围内（≤14天）快速评估个体肿瘤的治疗敏感性，才能实现基于精准医学的癌症治疗。我们的平台表明，这一目标可以实现，并为推进癌症精准医疗提供了令人信服的机会。
Most cancer treatment strategies target cell proliferation, angiogenesis, migration, and intravasation of tumor cells in an attempt to limit tumor growth and metastasis. An in vitro platform to assess tumor progression and drug sensitivity could provide avenues to enhance our understanding of tumor metastasis as well as precision medicine. We present a microfluidic platform that mimics biological mass transport near the arterial end of a capillary in the tumor microenvironment. A central feature is a quiescent perfused 3D microvascular network created prior to loading tumor cells or patient-derived tumor organoids in an adjacent compartment. The physiological delivery of nutrients and/or drugs to the tumor then occurs through the vascular network. We demonstrate the culture, growth, and treatment of tumor cell lines and patient-derived breast cancer organoids. The platform provides the opportunity to simultaneously and dynamically observe hallmark features of tumor progression including cell proliferation, angiogenesis, cell migration, and tumor cell intravasation. Additionally, primary breast tumor organoids are viable in the device for several weeks and induce robust sprouting angiogenesis. Finally, we demonstrate the feasibility of our platform for drug discovery and personalized medicine by analyzing the response to chemo- and anti-angiogenic therapy. Precision medicine-based cancer treatments can only be realized if individual tumors can be rapidly assessed for therapeutic sensitivity in a clinically relevant timeframe (≲14 days). Our platform indicates that this goal can be achieved and provides compelling opportunities to advance precision medicine for cancer.
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影响因子：
6.1
作者：
Alonzo LF;Moya ML;Shirure VS;George SC
通讯作者：
George SC
模拟血管微环境微流控芯片上肿瘤细胞行为的研究
影响因子：
4.6
作者：
Huang R;Zheng W;Liu W;Zhang W;Long Y;Jiang X
通讯作者：
Jiang X
DOI：
10.1073/pnas.0401064101
发表时间：
2004-04-06
影响因子：
11.1
作者：
Kuperwasser, C;Chavarria, T;Weinberg, RA
通讯作者：
Weinberg, RA
影响因子：
--
作者：
HUXLEY, VH;CURRY, FE;ADAMSON, RH
通讯作者：
ADAMSON, RH
影响因子：
4.6
作者：
Fan Y;Nguyen DT;Akay Y;Xu F;Akay M
通讯作者：
Akay M