TY - JOUR
T1 - Medium-Throughput Drug- and Radiotherapy Screening Assay using Patient-Derived Organoids
AU - Putker, Marrit
AU - Millen, Rosemary
AU - Overmeer, René
AU - Driehuis, Else
AU - Zandvliet, Maurice M J M
AU - Clevers, Hans
AU - Boj, Sylvia F
AU - Li, Qi-Xiang
PY - 2021/4/30
Y1 - 2021/4/30
N2 - Patient-derived organoid (PDO) models allow for long-term expansion and maintenance of primary epithelial cells grown in three dimensions and a near-native state. When derived from resected or biopsied tumor tissue, organoids closely recapitulate in vivo tumor morphology and can be used to study therapy response in vitro. Biobanks of tumor organoids reflect the vast variety of clinical tumors and patients and therefore hold great promise for preclinical and clinical applications. This paper presents a method for medium-throughput drug screening using head and neck squamous cell carcinoma and colorectal adenocarcinoma organoids. This approach can easily be adopted for use with any tissue-derived organoid model, both normal and diseased. Methods are described for in vitro exposure of organoids to chemo- and radiotherapy (either as single-treatment modality or in combination). Cell survival after 5 days of drug exposure is assessed by measuring adenosine triphosphate (ATP) levels. Drug sensitivity is measured by the half-maximal inhibitory concentration (IC50), area under the curve (AUC), and growth rate (GR) metrics. These parameters can provide insight into whether an organoid culture is deemed sensitive or resistant to a particular treatment.
AB - Patient-derived organoid (PDO) models allow for long-term expansion and maintenance of primary epithelial cells grown in three dimensions and a near-native state. When derived from resected or biopsied tumor tissue, organoids closely recapitulate in vivo tumor morphology and can be used to study therapy response in vitro. Biobanks of tumor organoids reflect the vast variety of clinical tumors and patients and therefore hold great promise for preclinical and clinical applications. This paper presents a method for medium-throughput drug screening using head and neck squamous cell carcinoma and colorectal adenocarcinoma organoids. This approach can easily be adopted for use with any tissue-derived organoid model, both normal and diseased. Methods are described for in vitro exposure of organoids to chemo- and radiotherapy (either as single-treatment modality or in combination). Cell survival after 5 days of drug exposure is assessed by measuring adenosine triphosphate (ATP) levels. Drug sensitivity is measured by the half-maximal inhibitory concentration (IC50), area under the curve (AUC), and growth rate (GR) metrics. These parameters can provide insight into whether an organoid culture is deemed sensitive or resistant to a particular treatment.
KW - Adenocarcinoma/drug therapy
KW - Antineoplastic Agents/pharmacology
KW - Colorectal Neoplasms/drug therapy
KW - Drug Evaluation, Preclinical/methods
KW - Head and Neck Neoplasms/drug therapy
KW - Humans
KW - Organ Culture Techniques
KW - Organoids/drug effects
KW - Squamous Cell Carcinoma of Head and Neck/drug therapy
U2 - 10.3791/62495
DO - 10.3791/62495
M3 - Article
C2 - 33999032
SN - 1940-087X
JO - Journal of Visualized Experiments
JF - Journal of Visualized Experiments
IS - 170
ER -