4.6 Article

Autofluorescence Imaging of Treatment Response in Neuroendocrine Tumor Organoids

期刊

CANCERS
卷 13, 期 8, 页码 -

出版社

MDPI
DOI: 10.3390/cancers13081873

关键词

fluorescence lifetime imaging; NAD(P)H; autofluorescence; neuroendocrine tumor; organoid

类别

资金

  1. NSF [CBET-1642287]
  2. Stand Up to Cancer [SU2C-AACR-IG-08-16, SU2C-AACR-PS-18]
  3. NIH [R01 CA185747, R01 CA205101, R01 CA211082, R21 CA224280, U01 TR002383, P30CA014520, R37CA226526, R37 CA226526]
  4. AlyWolff Foundation
  5. Putting Against Pancreatic Cancer
  6. University of Wisconsin Carbone Cancer Center [P30 CA014520]
  7. University of Wisconsin Carbone Cancer Center (UWCCC Pancreatic Cancer Taskforce)

向作者/读者索取更多资源

Gastroenteropancreatic neuroendocrine tumors (GEP-NET) make up around 60% of all neuroendocrine tumors, with low/intermediate grade human GEP-NETs having slow growth rates that traditional laboratory culture methods struggle to capture. The study explores the use of a label-free, non-destructive optical metabolic imaging (OMI) method to measure drug response in live GEP-NET patient-derived cancer organoids (PDCOs), showing promising results in testing drug combinations for GEP-NET treatment.
Simple Summary Gastroenteropancreatic neuroendocrine tumors (GEP-NET) account for roughly 60% of all neuroendocrine tumors, and low/intermediate grade human GEP-NETs have relatively slow growth rates that many laboratory culture methods fail to capture. Patient-derived cancer organoids (PDCOs) are an attractive model to address this need for relevant 3D cultures of GEP-NETs for laboratory drug testing. However, traditional measurements of drug response are not effective in GEP-NET PDCOs due to the small volume of tissue and slow growth rates that are characteristic of the disease. Here, we test a label-free, non-destructive optical metabolic imaging (OMI) method to measure drug response in live GEP-NET PDCOs. OMI measured a response to the novel treatment combination of ABT-263 and everolimus in five out of seven PDCO lines, at 72 h post-treatment. Overall, this work shows that OMI provides single-cell metabolic measurements of drug response in PDCOs to guide drug development for GEP-NET patients. Gastroenteropancreatic neuroendocrine tumors (GEP-NET) account for roughly 60% of all neuroendocrine tumors. Low/intermediate grade human GEP-NETs have relatively low proliferation rates that animal models and cell lines fail to recapitulate. Short-term patient-derived cancer organoids (PDCOs) are a 3D model system that holds great promise for recapitulating well-differentiated human GEP-NETs. However, traditional measurements of drug response (i.e., growth, proliferation) are not effective in GEP-NET PDCOs due to the small volume of tissue and low proliferation rates that are characteristic of the disease. Here, we test a label-free, non-destructive optical metabolic imaging (OMI) method to measure drug response in live GEP-NET PDCOs. OMI captures the fluorescence lifetime and intensity of endogenous metabolic cofactors NAD(P)H and FAD. OMI has previously provided accurate predictions of drug response on a single cell level in other cancer types, but this is the first study to apply OMI to GEP-NETs. OMI tested the response to novel drug combination on GEP-NET PDCOs, specifically ABT263 (navitoclax), a Bcl-2 family inhibitor, and everolimus, a standard GEP-NET treatment that inhibits mTOR. Treatment response to ABT263, everolimus, and the combination were tested in GEP-NET PDCO lines derived from seven patients, using two-photon OMI. OMI measured a response to the combination treatment in 5 PDCO lines, at 72 h post-treatment. In one of the non-responsive PDCO lines, heterogeneous response was identified with two distinct subpopulations of cell metabolism. Overall, this work shows that OMI provides single-cell metabolic measurements of drug response in PDCOs to guide drug development for GEP-NET patients.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.6
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据