Personalized models of heterogeneous 3D epithelial tumor microenvironments: Ovarian cancer as a model.
Personalized models of heterogeneous 3D epithelial tumor microenvironments: Ovarian cancer as a model.
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DOI：
10.1016/j.actbio.2021.04.041
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发表时间：
2021-09-15
影响因子：
9.7
通讯作者：
Mehta G
中科院分区：
文献类型：
--
作者：
Horst EN;Bregenzer ME;Mehta P;Snyder CS;Repetto T;Yang-Hartwich Y;Mehta G
癌症等棘手的人类疾病是依赖于具体情况的，对于个体患者和特定的肿瘤微环境来说都是独特的。然而，传统的癌症治疗通常是非特异性的，针对的是全球相似性而不是独特的驱动因素。这限制了不同患者群体甚至同一患者不同肿瘤位置的治疗效果。最终，这种较差的疗效可能导致较差的临床结果和难治性复发的发生。为了防止这种情况并改善结果，在选择患者的最佳辅助治疗时必须有选择性。在这篇综述中，我们假设使用个性化的肿瘤特异性疾病模型（TSM）作为实现这一非凡壮举的工具。首先，使用卵巢癌作为模型疾病，我们概述了肿瘤微环境中细胞和细胞外成分的异质性和复杂性。然后我们研究当代癌症模型的优点和缺点以及个性化 TSM 的基本原理。我们讨论如何通过使用现代分析技术对患者活检进行仔细而详细的分析来生成 TSM，并利用所得数据在体外构建精确的 3D 模型。最后，我们提供这些多功能个性化癌症模型的临床相关应用，以强调它们的潜在影响。这些模型可用于多种基础癌症生物学和转化研究。重要的是，这些方法可以扩展到其他癌症，促进新疗法的发现，更有效地针对每个患者 TME 的独特方面。
Intractable human diseases such as cancers, are context dependent, unique to both the individual patient and to the specific tumor microenvironment. However, conventional cancer treatments are often nonspecific, targeting global similarities rather than unique drivers. This limits treatment efficacy across heterogeneous patient populations and even at different tumor locations within the same patient. Ultimately, this poor efficacy can lead to poor clinical outcomes and the development of treatment-resistant relapse. To prevent this and improve outcomes, it is necessary to be selective when choosing a patient’s optimal adjuvant treatment. In this review, we posit the use of personalized, tumor-specific disease models (TSM) as tools to achieve this remarkable feat. First, using ovarian cancer as a model disease, we outline the heterogeneity and complexity of both the cellular and extracellular components in the tumor microenvironment. Then we examine the advantages and disadvantages of contemporary cancer models and the rationale for personalized TSM. We discuss how to generate TSM through careful and detailed analysis of patient biopsies with contemporary analysis techniques and utilizing the resultant data to construct precision 3D models in vitro. Finally, we provide clinically relevant applications of these versatile personalized cancer models to highlight their potential impact. These models have utility towards a myriad of fundamental cancer biology and translational studies. Importantly, these approaches can be extended to other carcinomas, facilitating the discovery of new therapeutics that more effectively target the unique aspects of each individual patient’s TME.
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影响因子：
--
作者：
Boesch M;Zeimet AG;Reimer D;Schmidt S;Gastl G;Parson W;Spoeck F;Hatina J;Wolf D;Sopper S
通讯作者：
Sopper S
DOI：
10.1039/c5ib00040h
发表时间：
2015-10
期刊：
Integrative biology : quantitative biosciences from nano to macro
影响因子：
--
作者：
Acerbi I;Cassereau L;Dean I;Shi Q;Au A;Park C;Chen YY;Liphardt J;Hwang ES;Weaver VM
通讯作者：
Weaver VM
影响因子：
4.3
作者：
Arnold, Shanna A.;Rivera, Lee B.;Brekken, Rolf A.
通讯作者：
Brekken, Rolf A.
影响因子：
4.8
作者：
Barbolina, Maria V.;Adley, Brian P.;Stack, M. Sharon
通讯作者：
Stack, M. Sharon
影响因子：
5.2
作者：
Alkmin, Samuel;Brodziski, Rebecca;Campagnola, Paul J.
通讯作者：
Campagnola, Paul J.