Evidence map›Paper›PMID 37013646›Full record

ArticleJournal of experimental & clinical cancer research : CR2023

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

George M Ramzy, Maxim Norkin, Thibaud Koessler, Lionel Voirol, Mathieu Tihy, Dina Hany, Thomas McKee, Frédéric Ris, Nicolas Buchs, Mylène Docquier and 6 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of experimental & clinical cancer research : CR, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed, 1 pooled it
4.8field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. Review
  5. Review
  6. Article
  7. Review
  8. Review
  9. Article
  10. Review
  11. Review
  12. Review
  13. Colorectal cancer: Recent advances in management and treatment.World journal of clinical oncology · 2024
    Review
  14. Review
  15. Review
  16. Review
  17. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors at 4 institutions in 2 countries.

George M RamzyMolecular Pharmacology Group, School of Pharmaceutical Sciences, University of Geneva, Rue Michel-Servet 1, CMU, 1211, Geneva 4, Switzerland.
Maxim NorkinSwiss Institute for Experimental Cancer Research (ISREC), Ecole Polytechnique Fédérale de Lausanne-(EPFL-SV), 1015, Lausanne, Switzerland.
Thibaud KoesslerDepartment of Oncology, Geneva University Hospitals, 1205, Geneva, Switzerland.
Lionel VoirolResearch Center for Statistics, Geneva School of Economics and Management, University of Geneva, 1205, Geneva, Switzerland.
Mathieu TihyDivision of Clinical Pathology, Diagnostic Department, University Hospitals of Geneva (HUG), 1205, Geneva, Switzerland.
Dina HanyMolecular Pharmacology Group, School of Pharmaceutical Sciences, University of Geneva, Rue Michel-Servet 1, CMU, 1211, Geneva 4, Switzerland.
Thomas McKeeDivision of Clinical Pathology, Diagnostic Department, University Hospitals of Geneva (HUG), 1205, Geneva, Switzerland.
Frédéric RisTranslational Department of Digestive and Transplant Surgery, Geneva University Hospitals and Faculty of Medicine, 1205, Geneva, Switzerland.
Nicolas BuchsTranslational Department of Digestive and Transplant Surgery, Geneva University Hospitals and Faculty of Medicine, 1205, Geneva, Switzerland.
Mylène DocquieriGE3 Genomics Platform, University of Geneva, 1211, Geneva, Switzerland.
Christian TosoDepartment of Visceral Surgery, Geneva University Hospital, 1211, Geneva, Switzerland.
Laura Rubbia-BrandtDivision of Clinical Pathology, Diagnostic Department, University Hospitals of Geneva (HUG), 1205, Geneva, Switzerland.
Gaetan BakalliEMLYON Business School, Artificial Intelligence in Management Institute, Ecully, France.
Stéphane GuerrierInstitute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, 1211, Geneva, Switzerland.
Joerg HuelskenSwiss Institute for Experimental Cancer Research (ISREC), Ecole Polytechnique Fédérale de Lausanne-(EPFL-SV), 1015, Lausanne, Switzerland.
Patrycja Nowak-SliwinskaMolecular Pharmacology Group, School of Pharmaceutical Sciences, University of Geneva, Rue Michel-Servet 1, CMU, 1211, Geneva 4, Switzerland. Patrycja.Nowak-Sliwinska@unige.ch.ORCID http://orcid.org/0000-0002-8299-0444
University Hospital of Geneva · CHUniversity of Geneva · CHÉcole Polytechnique Fédérale de Lausanne · CHÉcole de management de Lyon · FR

Funding

H2020 European Research Council ERC-StG-680209Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung 310030_197878
6 · The paper itself

Abstract

backgroundWe 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.

methodsThe 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.

resultsThe 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.

conclusionsOur approach allows the optimization of patient-tailored synergistic multi-drug combinations within a clinically relevant timeframe.

Indexed as

Colorectal NeoplasmsLiver NeoplasmsHumansLapatinibOrganoidsPrecision MedicineLapatinibDrug-drug interactionDrug resistanceMultidrug combinationOrganoidPhenotypic screenSynergyTargeted RNAseq

Identifiers

PMID37013646
PMCPMC10069117
OpenAlexW4362521910

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.