An in vitro vascularized micro-tumor model of human colorectal cancer recapitulates in vivo responses to standard-of-care therapy.
An in vitro vascularized micro-tumor model of human colorectal cancer recapitulates in vivo responses to standard-of-care therapy.
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DOI：
10.1039/d0lc01216e
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发表时间：
2021-04-07
期刊：
影响因子：
6.1
通讯作者：
Hughes CCW
中科院分区：
文献类型：
--
作者：
Hachey SJ;Movsesyan S;Nguyen QH;Burton-Sojo G;Tankazyan A;Wu J;Hoang T;Zhao D;Wang S;Hatch MM;Celaya E;Gomez S;Chen GT;Davis RT;Nee K;Pervolarakis N;Lawson DA;Kessenbrock K;Lee AP;Lowengrub J;Waterman ML;Hughes CCW
大约95%的抗癌药物在临床前研究中表现出希望，但未能获得FDA批准用于临床。这种临床前管道的失败突出了对改进的生理相关体外模型的需求，这些模型可以更好地作为可靠的药物筛选和疾病建模工具。血管化微肿瘤（VMT）是一种新型的三维模型系统（芯片上肿瘤），它在透明的微流体装置内重现了复杂的人类肿瘤微环境，包括灌注的脉管系统，允许实时研究药物反应和肿瘤-基质相互作用。在这里，我们已经验证了这种微生理系统（MPS）平台用于研究结直肠癌（CRC），癌症相关死亡的第二大原因，通过显示VMT中的基因表达，肿瘤异质性和治疗反应比目前的标准药物筛选模式（包括二维单层培养和三维球体）更接近CRC肿瘤临床病理学模型。VMT重现了体内药物反应，也重建了肿瘤的细胞多样性。
Around 95% of anti-cancer drugs that show promise during preclinical study fail to gain FDA-approval for clinical use. This failure of the preclinical pipeline highlights the need for improved, physiologically-relevant in vitro models that can better serve as reliable drug-screening and disease modeling tools. The vascularized micro-tumor (VMT) is a novel three-dimensional model system (tumor-on-a-chip) that recapitulates the complex human tumor microenvironment, including perfused vasculature, within a transparent microfluidic device, allowing real-time study of drug responses and tumor–stromal interactions. Here we have validated this microphysiological system (MPS) platform for the study of colorectal cancer (CRC), the second leading cause of cancer-related deaths, by showing that gene expression, tumor heterogeneity, and treatment responses in the VMT more closely model CRC tumor clinicopathology than current standard drug screening modalities, including 2-dimensional monolayer culture and 3-dimensional spheroids. VMTs recapitulate in vivo drug responses and also reconstitute the cellular diversity of tumors.
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影响因子：
24.3
作者：
Correia, Ana Luisa;Bissell, Mina J.
通讯作者：
Bissell, Mina J.
影响因子：
6.1
作者：
Hachey SJ;Hughes CCW
通讯作者：
Hughes CCW
影响因子：
64.8
作者：
Ghandi, Mahmoud;Huang, Franklin W.;Sellers, William R.
通讯作者：
Sellers, William R.
分子机制和血管生成的临床应用。
影响因子：
64.8
作者：
Carmeliet, Peter;Jain, Rakesh K.
通讯作者：
Jain, Rakesh K.
影响因子：
50.3
作者：
Calon A;Espinet E;Palomo-Ponce S;Tauriello DV;Iglesias M;Céspedes MV;Sevillano M;Nadal C;Jung P;Zhang XH;Byrom D;Riera A;Rossell D;Mangues R;Massagué J;Sancho E;Batlle E
通讯作者：
Batlle E