Non-small cell lung carcinoma spheroid models in agarose microwells for drug response studies.
Non-small cell lung carcinoma spheroid models in agarose microwells for drug response studies.
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DOI：
10.1039/d2lc00244b
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发表时间：
2022-06-14
期刊：
影响因子：
6.1
通讯作者：
Papautsky, Ian
中科院分区：
文献类型：
--
作者：
Luan, Qiyue;Becker, Jeffrey H.;Macaraniag, Celine;Massad, Malek G.;Zhou, Jian;Shimamura, Takeshi;Papautsky, Ian
人们越来越关注为每个癌症患者开发个性化治疗策略，特别是那些患有非小细胞肺癌（NSCLC）的患者，每年在美国占癌症相关死亡的大多数。然而，确定每个癌症患者的最佳NSCLC治疗策略是至关重要的，因为有许多突变，其中一些突变在初始治疗后发生，并可能导致耐药性。在NSCLC中开发个性化治疗的一个关键困难是缺乏临床相关的检测系统，该系统适用于使用活检后可获得的极少量患者来源的材料来评估药物敏感性。在这里，我们利用3D打印来展示基于琼脂糖中的微型微孔的平台，以培养癌细胞球状体。琼脂糖威尔斯孔通过3D打印模具成形，模具具有1000个具有U形底部的微孔威尔斯。使用三种NSCLC细胞系（HCC 4006、H1975和A549）来证明3D琼脂糖微孔中的大小均匀性、球体活力、生物标志物表达和药物响应。结果表明，我们的方法产生了大小均匀（变异系数<22%）和高活力（培养1周后>83%）的球状体。使用表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKI）药物吉非替尼和奥希替尼的研究显示了临床相关的反应。基于我们的球体模型的物理特征、细胞表型和对治疗的反应，我们得出结论，我们的平台适用于体外培养和药物评价，特别是在肿瘤样本有限的情况下。
There is a growing interest in developing personalized treatment strategies for each cancer patient, especially those with non-small cell lung carcinoma (NSCLC) which annually accounts for the majority of cancer related deaths in the US. Yet identifying the optimal NSCLC treatment strategy for each cancer patient is critical due to a multitude of mutations, some of which develop following initial therapy and can result in drug resistance. A key difficulty in developing personalized therapies in NSCLC is the lack of clinically relevant assay systems that are suitable to evaluate drug sensitivity using a minuscule amount of patient-derived material available following biopsies. Herein we leverage 3D printing to demonstrate a platform based on miniature microwells in agarose to culture cancer cell spheroids. The agarose wells were shaped by 3D printing molds with 1000 microwells with a U-shaped bottom. Three NSCLC cell lines (HCC4006, H1975 and A549) were used to demonstrate size uniformity, spheroid viability, biomarker expressions and drug response in 3D agarose microwells. Results show that our approach yielded spheroids of uniform size (coefficient of variation <22%) and high viability (>83% after 1 week-culture). Studies using epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKIs) drugs gefitinib and osimertinib showed clinically relevant responses. Based on the physical features, cell phenotypes, and responses to therapy of our spheroid models, we conclude that our platform is suitable for in vitro culture and drug evaluation, especially in cases when tumor sample is limited.
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影响因子：
6.1
作者：
de Groot TE;Veserat KS;Berthier E;Beebe DJ;Theberge AB
通讯作者：
Theberge AB
影响因子：
3.4
作者：
Amadeo F;Mukherjee P;Gao H;Zhou J;Papautsky I
通讯作者：
Papautsky I
DOI：
10.1088/0960-1317/25/3/035005
发表时间：
2015-03-01
影响因子：
2.3
作者：
Lee, Gi-Hun;Kim, Sung-Hwan;Park, Joong Yull
通讯作者：
Park, Joong Yull
KRAS突变肺癌的当前疗法。
DOI：
10.1007/s10555-020-09903-9
发表时间：
2020-12
期刊：
Cancer metastasis reviews
影响因子：
--
作者：
Ghimessy A;Radeczky P;Laszlo V;Hegedus B;Renyi-Vamos F;Fillinger J;Klepetko W;Lang C;Dome B;Megyesfalvi Z
通讯作者：
Megyesfalvi Z
影响因子：
3.4
作者：
Kress, Sebastian;Schaller-Ammann, Roland;Egger, Dominik
通讯作者：
Egger, Dominik