Single-organoid analysis reveals clinically relevant treatment-resistant and invasive subclones in pancreatic cancer
Abstract Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal diseases, characterized by a treatment-resistant and invasive nature. In line with these inherent aggressive characteristics, only a subset of patients shows a clinical response to the standard of care therapies, thereby high...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-12-01
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| Series: | npj Precision Oncology |
| Online Access: | https://doi.org/10.1038/s41698-023-00480-y |
| _version_ | 1827590770960367616 |
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| author | Maxim Le Compte Edgar Cardenas De La Hoz Sofía Peeters Felicia Rodrigues Fortes Christophe Hermans Andreas Domen Evelien Smits Filip Lardon Timon Vandamme Abraham Lin Steve Vanlanduit Geert Roeyen Steven Van Laere Hans Prenen Marc Peeters Christophe Deben |
| author_facet | Maxim Le Compte Edgar Cardenas De La Hoz Sofía Peeters Felicia Rodrigues Fortes Christophe Hermans Andreas Domen Evelien Smits Filip Lardon Timon Vandamme Abraham Lin Steve Vanlanduit Geert Roeyen Steven Van Laere Hans Prenen Marc Peeters Christophe Deben |
| author_sort | Maxim Le Compte |
| collection | DOAJ |
| description | Abstract Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal diseases, characterized by a treatment-resistant and invasive nature. In line with these inherent aggressive characteristics, only a subset of patients shows a clinical response to the standard of care therapies, thereby highlighting the need for a more personalized treatment approach. In this study, we comprehensively unraveled the intra-patient response heterogeneity and intrinsic aggressive nature of PDAC on bulk and single-organoid resolution. We leveraged a fully characterized PDAC organoid panel (N = 8) and matched our artificial intelligence-driven, live-cell organoid image analysis with retrospective clinical patient response. In line with the clinical outcomes, we identified patient-specific sensitivities to the standard of care therapies (gemcitabine-paclitaxel and FOLFIRINOX) using a growth rate-based and normalized drug response metric. Moreover, the single-organoid analysis was able to detect resistant as well as invasive PDAC organoid clones, which was orchestrates on a patient, therapy, drug, concentration and time-specific level. Furthermore, our in vitro organoid analysis indicated a correlation with the matched patient progression-free survival (PFS) compared to the current, conventional drug response readouts. This work not only provides valuable insights on the response complexity in PDAC, but it also highlights the potential applications (extendable to other tumor types) and clinical translatability of our approach in drug discovery and the emerging era of personalized medicine. |
| first_indexed | 2024-03-09T01:21:28Z |
| format | Article |
| id | doaj.art-6632e8a47737498b80b21ca813df1b57 |
| institution | Directory Open Access Journal |
| issn | 2397-768X |
| language | English |
| last_indexed | 2024-03-09T01:21:28Z |
| publishDate | 2023-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Precision Oncology |
| spelling | doaj.art-6632e8a47737498b80b21ca813df1b572023-12-10T12:05:47ZengNature Portfolionpj Precision Oncology2397-768X2023-12-017111410.1038/s41698-023-00480-ySingle-organoid analysis reveals clinically relevant treatment-resistant and invasive subclones in pancreatic cancerMaxim Le Compte0Edgar Cardenas De La Hoz1Sofía Peeters2Felicia Rodrigues Fortes3Christophe Hermans4Andreas Domen5Evelien Smits6Filip Lardon7Timon Vandamme8Abraham Lin9Steve Vanlanduit10Geert Roeyen11Steven Van Laere12Hans Prenen13Marc Peeters14Christophe Deben15Center for Oncological Research (CORE), Integrated Personalized & Precision Oncology Network (IPPON), University of AntwerpIndustrial Vision Lab, University of AntwerpCenter for Oncological Research (CORE), Integrated Personalized & Precision Oncology Network (IPPON), University of AntwerpCenter for Oncological Research (CORE), Integrated Personalized & Precision Oncology Network (IPPON), University of AntwerpCenter for Oncological Research (CORE), Integrated Personalized & Precision Oncology Network (IPPON), University of AntwerpCenter for Oncological Research (CORE), Integrated Personalized & Precision Oncology Network (IPPON), University of AntwerpCenter for Oncological Research (CORE), Integrated Personalized & Precision Oncology Network (IPPON), University of AntwerpCenter for Oncological Research (CORE), Integrated Personalized & Precision Oncology Network (IPPON), University of AntwerpCenter for Oncological Research (CORE), Integrated Personalized & Precision Oncology Network (IPPON), University of AntwerpCenter for Oncological Research (CORE), Integrated Personalized & Precision Oncology Network (IPPON), University of AntwerpIndustrial Vision Lab, University of AntwerpCenter for Oncological Research (CORE), Integrated Personalized & Precision Oncology Network (IPPON), University of AntwerpCenter for Oncological Research (CORE), Integrated Personalized & Precision Oncology Network (IPPON), University of AntwerpCenter for Oncological Research (CORE), Integrated Personalized & Precision Oncology Network (IPPON), University of AntwerpCenter for Oncological Research (CORE), Integrated Personalized & Precision Oncology Network (IPPON), University of AntwerpCenter for Oncological Research (CORE), Integrated Personalized & Precision Oncology Network (IPPON), University of AntwerpAbstract Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal diseases, characterized by a treatment-resistant and invasive nature. In line with these inherent aggressive characteristics, only a subset of patients shows a clinical response to the standard of care therapies, thereby highlighting the need for a more personalized treatment approach. In this study, we comprehensively unraveled the intra-patient response heterogeneity and intrinsic aggressive nature of PDAC on bulk and single-organoid resolution. We leveraged a fully characterized PDAC organoid panel (N = 8) and matched our artificial intelligence-driven, live-cell organoid image analysis with retrospective clinical patient response. In line with the clinical outcomes, we identified patient-specific sensitivities to the standard of care therapies (gemcitabine-paclitaxel and FOLFIRINOX) using a growth rate-based and normalized drug response metric. Moreover, the single-organoid analysis was able to detect resistant as well as invasive PDAC organoid clones, which was orchestrates on a patient, therapy, drug, concentration and time-specific level. Furthermore, our in vitro organoid analysis indicated a correlation with the matched patient progression-free survival (PFS) compared to the current, conventional drug response readouts. This work not only provides valuable insights on the response complexity in PDAC, but it also highlights the potential applications (extendable to other tumor types) and clinical translatability of our approach in drug discovery and the emerging era of personalized medicine.https://doi.org/10.1038/s41698-023-00480-y |
| spellingShingle | Maxim Le Compte Edgar Cardenas De La Hoz Sofía Peeters Felicia Rodrigues Fortes Christophe Hermans Andreas Domen Evelien Smits Filip Lardon Timon Vandamme Abraham Lin Steve Vanlanduit Geert Roeyen Steven Van Laere Hans Prenen Marc Peeters Christophe Deben Single-organoid analysis reveals clinically relevant treatment-resistant and invasive subclones in pancreatic cancer npj Precision Oncology |
| title | Single-organoid analysis reveals clinically relevant treatment-resistant and invasive subclones in pancreatic cancer |
| title_full | Single-organoid analysis reveals clinically relevant treatment-resistant and invasive subclones in pancreatic cancer |
| title_fullStr | Single-organoid analysis reveals clinically relevant treatment-resistant and invasive subclones in pancreatic cancer |
| title_full_unstemmed | Single-organoid analysis reveals clinically relevant treatment-resistant and invasive subclones in pancreatic cancer |
| title_short | Single-organoid analysis reveals clinically relevant treatment-resistant and invasive subclones in pancreatic cancer |
| title_sort | single organoid analysis reveals clinically relevant treatment resistant and invasive subclones in pancreatic cancer |
| url | https://doi.org/10.1038/s41698-023-00480-y |
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