دورية أكاديمية
أعرض في EDS

Platform combining statistical modeling and patient-derived organoids to facilitate personalized treatment of colorectal carcinoma.

التفاصيل البيبلوغرافية
العنوان: Platform combining statistical modeling and patient-derived organoids to facilitate personalized treatment of colorectal carcinoma.
المؤلفون: Ramzy GM; Molecular Pharmacology Group, School of Pharmaceutical Sciences, University of Geneva, Rue Michel-Servet 1, CMU, 1211, Geneva 4, Switzerland.; Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, 1211, Geneva, Switzerland.; Translational Research Center in Oncohaematology, 1211, Geneva, Switzerland., Norkin M; Swiss Institute for Experimental Cancer Research (ISREC), Ecole Polytechnique Fédérale de Lausanne-(EPFL-SV), 1015, Lausanne, Switzerland., Koessler T; Department of Oncology, Geneva University Hospitals, 1205, Geneva, Switzerland., Voirol L; Research Center for Statistics, Geneva School of Economics and Management, University of Geneva, 1205, Geneva, Switzerland., Tihy M; Division of Clinical Pathology, Diagnostic Department, University Hospitals of Geneva (HUG), 1205, Geneva, Switzerland., Hany D; Molecular Pharmacology Group, School of Pharmaceutical Sciences, University of Geneva, Rue Michel-Servet 1, CMU, 1211, Geneva 4, Switzerland.; Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, 1211, Geneva, Switzerland.; Translational Research Center in Oncohaematology, 1211, Geneva, Switzerland., McKee T; Division of Clinical Pathology, Diagnostic Department, University Hospitals of Geneva (HUG), 1205, Geneva, Switzerland., Ris F; Translational Department of Digestive and Transplant Surgery, Geneva University Hospitals and Faculty of Medicine, 1205, Geneva, Switzerland., Buchs N; Translational Department of Digestive and Transplant Surgery, Geneva University Hospitals and Faculty of Medicine, 1205, Geneva, Switzerland., Docquier M; iGE3 Genomics Platform, University of Geneva, 1211, Geneva, Switzerland.; Department of Genetics & Evolution, University of Geneva, 1211, Geneva, Switzerland., Toso C; Department of Visceral Surgery, Geneva University Hospital, 1211, Geneva, Switzerland., Rubbia-Brandt L; Division of Clinical Pathology, Diagnostic Department, University Hospitals of Geneva (HUG), 1205, Geneva, Switzerland., Bakalli G; EMLYON Business School, Artificial Intelligence in Management Institute, Ecully, France., Guerrier S; Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, 1211, Geneva, Switzerland.; Research Center for Statistics, Geneva School of Economics and Management, University of Geneva, 1205, Geneva, Switzerland., Huelsken J; Swiss Institute for Experimental Cancer Research (ISREC), Ecole Polytechnique Fédérale de Lausanne-(EPFL-SV), 1015, Lausanne, Switzerland., Nowak-Sliwinska P; Molecular Pharmacology Group, School of Pharmaceutical Sciences, University of Geneva, Rue Michel-Servet 1, CMU, 1211, Geneva 4, Switzerland. Patrycja.Nowak-Sliwinska@unige.ch.; Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, 1211, Geneva, Switzerland. Patrycja.Nowak-Sliwinska@unige.ch.; Translational Research Center in Oncohaematology, 1211, Geneva, Switzerland. Patrycja.Nowak-Sliwinska@unige.ch.
المصدر: Journal of experimental & clinical cancer research : CR [J Exp Clin Cancer Res] 2023 Apr 03; Vol. 42 (1), pp. 79. Date of Electronic Publication: 2023 Apr 03.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: BioMed Central Country of Publication: England NLM ID: 8308647 Publication Model: Electronic Cited Medium: Internet ISSN: 1756-9966 (Electronic) Linking ISSN: 03929078 NLM ISO Abbreviation: J Exp Clin Cancer Res Subsets: MEDLINE
أسماء مطبوعة: Publication: 2009- : London : BioMed Central
Original Publication: [Roma] : APSIT,
مواضيع طبية MeSH: Colorectal Neoplasms*/drug therapy , Colorectal Neoplasms*/genetics , Colorectal Neoplasms*/pathology , Liver Neoplasms*/drug therapy , Liver Neoplasms*/genetics , Liver Neoplasms*/pathology, Humans ; Precision Medicine/methods ; Lapatinib ; Organoids
مستخلص: Background: We propose a new approach for designing personalized treatment for colorectal cancer (CRC) patients, by combining ex vivo organoid efficacy testing with mathematical modeling of the results.
Methods: The validated phenotypic approach called Therapeutically Guided Multidrug Optimization (TGMO) was used to identify four low-dose synergistic optimized drug combinations (ODC) in 3D human CRC models of cells that are either sensitive or resistant to first-line CRC chemotherapy (FOLFOXIRI). Our findings were obtained using second order linear regression and adaptive lasso.
Results: The activity of all ODCs was validated on patient-derived organoids (PDO) from cases with either primary or metastatic CRC. The CRC material was molecularly characterized using whole-exome sequencing and RNAseq. In PDO from patients with liver metastases (stage IV) identified as CMS4/CRIS-A, our ODCs consisting of regorafenib [1 mM], vemurafenib [11 mM], palbociclib [1 mM] and lapatinib [0.5 mM] inhibited cell viability up to 88%, which significantly outperforms FOLFOXIRI administered at clinical doses. Furthermore, we identified patient-specific TGMO-based ODCs that outperform the efficacy of the current chemotherapy standard of care, FOLFOXIRI.
Conclusions: Our approach allows the optimization of patient-tailored synergistic multi-drug combinations within a clinically relevant timeframe.
(© 2023. The Author(s).)
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معلومات مُعتمدة: 310030_197878 Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung; ERC-StG-680209 H2020 European Research Council
فهرسة مساهمة: Keywords: Drug resistance; Drug-drug interaction; Multidrug combination; Organoid; Phenotypic screen; Synergy; Targeted RNAseq
المشرفين على المادة: 0VUA21238F (Lapatinib)
تواريخ الأحداث: Date Created: 20230404 Date Completed: 20230405 Latest Revision: 20230406
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC10069117
DOI: 10.1186/s13046-023-02650-z
PMID: 37013646
قاعدة البيانات: MEDLINE
الوصف
تدمد:1756-9966
DOI:10.1186/s13046-023-02650-z