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A new approach for realizing the "antioncogram"
1Institut für Anatomie, Freie Universität Berlin, Germany.
Abstract:
On the basis of an organoid culture method which allows organoid reorganization and histotypical growth of human carcinomas under in vitro conditions, we propose in the present study an organoid culture assay (OCA) as "antioncogram", i.e., as in vitro model for testing the drug sensitivity and resistance of individual patients' carcinomas previous to clinical chemotherapy. At the beginning of the assay, specimens of human carcinomas are disaggregated to dense single cell suspensions and dropped on a filter sheet at the air-medium interface. Organoid culture nodules develop within several days to weeks. They are exposed to cytostatics by adding the drugs for 2-3 days to the growth medium below the filter sheet. At the end of the exposure period, the cytotoxic effects are estimated by determining the fraction of viable cells, measured by the uptake of neutral red in relation to the total cell mass. In the present study we could show that this assay actually reflects the different levels of experimentally induced resistance of three human carcinoma strains of an epidermoid hypopharynx carcinoma to the cytostatic drug cisplatin and is obviously suited to predict the response of individual human carcinomas to chemotherapy in a rapid and feasible manner.
Insights
This study introduces an organoid culture assay (OCA) to predict patient carcinoma drug response before chemotherapy. The assay tests drug sensitivity and resistance using patient tumor samples in vitro for personalized cancer treatment.
Area of Science:
- Oncology
- Cell Biology
- Biotechnology
Background:
- Carcinoma drug resistance poses a significant challenge in clinical chemotherapy.
- Predicting individual patient response to chemotherapy is crucial for effective treatment.
Purpose of the Study:
- To develop and validate an organoid culture assay (OCA) as an "antioncogram" for predicting patient-specific carcinoma drug sensitivity.
- To establish an in vitro model for assessing drug resistance in human carcinomas prior to clinical application.
Main Methods:
- Human carcinoma specimens were disaggregated into single cell suspensions and cultured as organoids on filter sheets.
- Organoids were exposed to cytostatics (cisplatin) for 2-3 days.
- Cytotoxic effects were quantified by measuring viable cell fraction (neutral red uptake) relative to total cell mass.
Main Results:
- The organoid culture assay (OCA) successfully reflected experimentally induced cisplatin resistance in epidermoid hypopharynx carcinoma strains.
- The assay demonstrated its suitability for rapid and feasible prediction of individual human carcinoma responses to chemotherapy.
Conclusions:
- The organoid culture assay (OCA) serves as a viable "antioncogram" for personalized cancer therapy.
- This in vitro method can guide clinical chemotherapy decisions by predicting drug sensitivity and resistance.