The drug efficacy testing in 3D cultures platform identifies effective drugs for ovarian cancer patients
Abstract Most patients with advanced ovarian cancer (OC) relapse and progress despite systemic therapy, pointing to the need for improved and tailored therapy options. Functional precision medicine can help to identify effective therapies for individual patients in a clinically relevant timeframe. H...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-10-01
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| Series: | npj Precision Oncology |
| Online Access: | https://doi.org/10.1038/s41698-023-00463-z |
| _version_ | 1797637150709121024 |
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| author | Emma Åkerlund Greta Gudoityte Elisabeth Moussaud-Lamodière Olina Lind Henri Colyn Bwanika Kaisa Lehti Sahar Salehi Joseph Carlson Emelie Wallin Josefin Fernebro Päivi Östling Olli Kallioniemi Ulrika Joneborg Brinton Seashore-Ludlow |
| author_facet | Emma Åkerlund Greta Gudoityte Elisabeth Moussaud-Lamodière Olina Lind Henri Colyn Bwanika Kaisa Lehti Sahar Salehi Joseph Carlson Emelie Wallin Josefin Fernebro Päivi Östling Olli Kallioniemi Ulrika Joneborg Brinton Seashore-Ludlow |
| author_sort | Emma Åkerlund |
| collection | DOAJ |
| description | Abstract Most patients with advanced ovarian cancer (OC) relapse and progress despite systemic therapy, pointing to the need for improved and tailored therapy options. Functional precision medicine can help to identify effective therapies for individual patients in a clinically relevant timeframe. Here, we present a scalable functional precision medicine platform: DET3Ct (Drug Efficacy Testing in 3D Cultures), where the response of patient cells to drugs and drug combinations are quantified with live-cell imaging. We demonstrate the delivery of individual drug sensitivity profiles in 20 samples from 16 patients with ovarian cancer in both 2D and 3D culture formats, achieving over 90% success rate in providing results six days after operation. In this cohort all patients received carboplatin. The carboplatin sensitivity scores were significantly different for patients with a progression free interval (PFI) less than or equal to 12 months and those with more than 12 months (p < 0.05). We find that the 3D culture format better retains proliferation and characteristics of the in vivo setting. Using the DET3Ct platform we evaluate 27 tailored combinations with results available 10 days after operation. Notably, carboplatin and A-1331852 (Bcl-xL inhibitor) showed an additive effect in four of eight OC samples tested, while afatinib and A-1331852 led to synergy in five of seven OC models. In conclusion, our 3D DET3Ct platform can rapidly define potential, clinically relevant data on efficacy of existing drugs in OC for precision medicine purposes, as well as provide insights on emerging drugs and drug combinations that warrant testing in clinical trials. |
| first_indexed | 2024-03-11T12:45:16Z |
| format | Article |
| id | doaj.art-f9a11623e752413883774ad582a47d05 |
| institution | Directory Open Access Journal |
| issn | 2397-768X |
| language | English |
| last_indexed | 2024-03-11T12:45:16Z |
| publishDate | 2023-10-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Precision Oncology |
| spelling | doaj.art-f9a11623e752413883774ad582a47d052023-11-05T12:06:18ZengNature Portfolionpj Precision Oncology2397-768X2023-10-017111310.1038/s41698-023-00463-zThe drug efficacy testing in 3D cultures platform identifies effective drugs for ovarian cancer patientsEmma Åkerlund0Greta Gudoityte1Elisabeth Moussaud-Lamodière2Olina Lind3Henri Colyn Bwanika4Kaisa Lehti5Sahar Salehi6Joseph Carlson7Emelie Wallin8Josefin Fernebro9Päivi Östling10Olli Kallioniemi11Ulrika Joneborg12Brinton Seashore-Ludlow13Science for Life Laboratory, Department of Oncology-Pathology, Karolinska InstituteScience for Life Laboratory, Department of Oncology-Pathology, Karolinska InstituteScience for Life Laboratory, Department of Oncology-Pathology, Karolinska InstituteScience for Life Laboratory, Department of Oncology-Pathology, Karolinska Institute Department of Oncology-Pathology, Karolinska InstituteDepartment of Biomedical Laboratory Science, Norwegian University of Science and Technology NTNUDepartment of Microbiology, Tumor and Cell Biology, Karolinska InstitutetDepartment of Pathology and Laboratory Medicine, Keck School of Medicine, University of Southern California Department of Oncology-Pathology, Karolinska InstituteDepartment of Women’s and Children’s Health, Division of Obstetrics and Gynecology, Karolinska InstitutetScience for Life Laboratory, Department of Oncology-Pathology, Karolinska InstituteScience for Life Laboratory, Department of Oncology-Pathology, Karolinska InstituteDepartment of Pelvic Cancer, Theme Cancer, Karolinska University HospitalScience for Life Laboratory, Department of Oncology-Pathology, Karolinska InstituteAbstract Most patients with advanced ovarian cancer (OC) relapse and progress despite systemic therapy, pointing to the need for improved and tailored therapy options. Functional precision medicine can help to identify effective therapies for individual patients in a clinically relevant timeframe. Here, we present a scalable functional precision medicine platform: DET3Ct (Drug Efficacy Testing in 3D Cultures), where the response of patient cells to drugs and drug combinations are quantified with live-cell imaging. We demonstrate the delivery of individual drug sensitivity profiles in 20 samples from 16 patients with ovarian cancer in both 2D and 3D culture formats, achieving over 90% success rate in providing results six days after operation. In this cohort all patients received carboplatin. The carboplatin sensitivity scores were significantly different for patients with a progression free interval (PFI) less than or equal to 12 months and those with more than 12 months (p < 0.05). We find that the 3D culture format better retains proliferation and characteristics of the in vivo setting. Using the DET3Ct platform we evaluate 27 tailored combinations with results available 10 days after operation. Notably, carboplatin and A-1331852 (Bcl-xL inhibitor) showed an additive effect in four of eight OC samples tested, while afatinib and A-1331852 led to synergy in five of seven OC models. In conclusion, our 3D DET3Ct platform can rapidly define potential, clinically relevant data on efficacy of existing drugs in OC for precision medicine purposes, as well as provide insights on emerging drugs and drug combinations that warrant testing in clinical trials.https://doi.org/10.1038/s41698-023-00463-z |
| spellingShingle | Emma Åkerlund Greta Gudoityte Elisabeth Moussaud-Lamodière Olina Lind Henri Colyn Bwanika Kaisa Lehti Sahar Salehi Joseph Carlson Emelie Wallin Josefin Fernebro Päivi Östling Olli Kallioniemi Ulrika Joneborg Brinton Seashore-Ludlow The drug efficacy testing in 3D cultures platform identifies effective drugs for ovarian cancer patients npj Precision Oncology |
| title | The drug efficacy testing in 3D cultures platform identifies effective drugs for ovarian cancer patients |
| title_full | The drug efficacy testing in 3D cultures platform identifies effective drugs for ovarian cancer patients |
| title_fullStr | The drug efficacy testing in 3D cultures platform identifies effective drugs for ovarian cancer patients |
| title_full_unstemmed | The drug efficacy testing in 3D cultures platform identifies effective drugs for ovarian cancer patients |
| title_short | The drug efficacy testing in 3D cultures platform identifies effective drugs for ovarian cancer patients |
| title_sort | drug efficacy testing in 3d cultures platform identifies effective drugs for ovarian cancer patients |
| url | https://doi.org/10.1038/s41698-023-00463-z |
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