Development and validation of the Normalized Organoid Growth Rate (NOGR) metric in brightfield imaging-based assays
This study focuses on refining growth-rate-based drug response metrics for patient-derived tumor organoid screening using brightfield live-cell imaging. Traditional metrics like Normalized Growth Rate Inhibition (GR) and Normalized Drug Response (NDR) have been used to assess organoid responses to anticancer treatments but face limitations in accurately quantifying cytostatic and cytotoxic effects across varying growth rates. Here, we introduce the Normalized Organoid Growth Rate (NOGR) metric, specifically developed for brightfield imaging-based assays. A label-free image analysis model was applied to segment organoids precisely, track their growth rates over time, and classify viable and dead organoids. Testing eleven phenotypically distinct pancreatic cancer organoid models with five chemotherapeutics demonstrates that the NOGR metric more effectively captures cytostatic and cytotoxic drug effects compared to existing methods. This approach enhances the biological relevance of drug sensitivity assessments on organoids and offers a valuable tool for advancing personalized cancer treatment strategies.
Authors
- Edgar Cardenas De La Hoz (ORCID: https://orcid.org/0000-0002-5098-3207)
- Nelson Dusetti (ORCID: https://orcid.org/0000-0002-6161-8483)
- Maxim Le Compte (ORCID: https://orcid.org/0000-0002-5587-4392)
- Filip Lardon (ORCID: https://orcid.org/0000-0001-7174-4144)
- Abraham Lin (ORCID: https://orcid.org/0000-0003-0097-3323)
- Marc Peeters (ORCID: https://orcid.org/0000-0003-4969-2303)
- Felicia Rodrigues Fortes
- Bert Van Den Bogert
- Hans Prenen (ORCID: https://orcid.org/0000-0001-8802-7352)
- Geert Roeyen (ORCID: https://orcid.org/0000-0003-2947-1407)
- Evelien Smits (ORCID: https://orcid.org/0000-0001-9255-3435)
- H. Vercammen (ORCID: https://orcid.org/0000-0002-1881-3523)
- Steve Vanlanduit (ORCID: https://orcid.org/0000-0002-7975-1338)
- Christophe Deben (ORCID: https://orcid.org/0000-0001-8085-2040)
- Sofie Seghers (ORCID: https://orcid.org/0000-0002-2438-4155)
Institutions
- Centre National de la Recherche Scientifique (FR)
- University of Antwerp (BE)
- Inserm (FR)
- Aix-Marseille Université (FR)
- Antwerp University Hospital (BE)
- Centre de Recherche en Cancérologie de Marseille (FR)
Publication Details
- Journal
- Communications Biology
- Published
- 2024-12-03
- DOI
- https://doi.org/10.1038/s42003-024-07329-5
- Citations
- 16
- Primary Topic
- Cancer Cells and Metastasis
- Type
- article
- Field-Weighted Citation Impact
- 4.52
Funders
- Fonds Wetenschappelijk Onderzoek
- Universiteit Antwerpen
- Vlaamse regering