From Chemotherapy to Combined Targeted Therapeutics: In Vitro and in Vivo Models to Decipher Intra-tumor Heterogeneity.
From Chemotherapy to Combined Targeted Therapeutics: In Vitro and in Vivo Models to Decipher Intra-tumor Heterogeneity.
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DOI：
10.3389/fphar.2018.00077
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发表时间：
2018
影响因子：
5.6
通讯作者：
Silvestri A
中科院分区：
文献类型：
--
作者：
Gambara G;Gaebler M;Keilholz U;Regenbrecht CRA;Silvestri A
新一代测序和其他能够绘制细胞命运的组学技术的最新进展为肿瘤内异质性（ITH）对癌症进展的关键作用提供了越来越多的证据。ITH的不同方面，从基因组到微环境异质性和起源于癌症干细胞区室的分层细胞结构，有助于肿瘤表型的范围。解码这些由肿瘤组织复杂性分析产生的复杂数据对开发可以对抗肿瘤演变和细胞可塑性的新型治疗策略提出了挑战。为了实现这一目标，开发类似ITH复杂性的体外和体内癌症模型对于理解细胞及其（微）环境的相互作用至关重要，因此，对于测试新靶向治疗的疗效和针对肿瘤个体组成定制治疗组合的新策略至关重要。这种具有挑战性的方法可能是克服多线治疗期间药物抗性发展的重要基石。在本文中，我们报告了患者来源的3D（PD3D）细胞培养物和患者来源的肿瘤异种移植物（PDX）作为体外和体内模型的最新进展，这些模型可以保留肿瘤组织的遗传和表型异质性。
Recent advances in next-generation sequencing and other omics technologies capable to map cell fate provide increasing evidence on the crucial role of intra-tumor heterogeneity (ITH) for cancer progression. The different facets of ITH, from genomic to microenvironmental heterogeneity and the hierarchical cellular architecture originating from the cancer stem cell compartment, contribute to the range of tumor phenotypes. Decoding these complex data resulting from the analysis of tumor tissue complexity poses a challenge for developing novel therapeutic strategies that can counteract tumor evolution and cellular plasticity. To achieve this aim, the development of in vitro and in vivo cancer models that resemble the complexity of ITH is crucial in understanding the interplay of cells and their (micro)environment and, consequently, in testing the efficacy of new targeted treatments and novel strategies of tailoring combinations of treatments to the individual composition of the tumor. This challenging approach may be an important cornerstone in overcoming the development of pharmaco-resistances during multiple lines of treatment. In this paper, we report the latest advances in patient-derived 3D (PD3D) cell cultures and patient-derived tumor xenografts (PDX) as in vitro and in vivo models that can retain the genetic and phenotypic heterogeneity of the tumor tissue.
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影响因子：
64.8
作者：
通讯作者：
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影响因子：
7.7
作者：
Bozic I;Reiter JG;Allen B;Antal T;Chatterjee K;Shah P;Moon YS;Yaqubie A;Kelly N;Le DT;Lipson EJ;Chapman PB;Diaz LA Jr;Vogelstein B;Nowak MA
通讯作者：
Nowak MA
影响因子：
64.8
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影响因子：
11.2
作者：
Carey JPW;Karakas C;Bui T;Chen X;Vijayaraghavan S;Zhao Y;Wang J;Mikule K;Litton JK;Hunt KK;Keyomarsi K
通讯作者：
Keyomarsi K
影响因子：
4.7
作者：
Augsten M
通讯作者：
Augsten M