Medium-Throughput Drug- and Radiotherapy Screening Assay using Patient-Derived Organoids

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 -