ArticleJournal of experimental & clinical cancer research : CR2023
"Proteotranscriptomic analysis of advanced colorectal cancer patient derived organoids for drug sensitivity prediction".
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 50 papers.
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Who cites it
50 citing papers in PubMed, 85 citations in OpenAlex.
- A Phase II Exploratory Study to Identify Biomarkers Predictive of Clinical Response to Regorafenib in Patients with Metastatic Colorectal Cancer Who Have Failed First-Line Therapy.International journal of molecular sciences · 2023Trial
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- Deconstructing cancer in 3D: models, mechanisms, and personalized solutions.Molecular cancer · 2026Review
- Organoid models: Regulations and prospects for the development of investigational new drugs.Chinese medical journal · 2026Review
- Predicting therapeutic responses in metastatic colorectal cancer through personalized functional profiling of patient-derived spheroids.NPJ precision oncology · 2026Article
- Expression, Prognostic Value, and Biological Function of CENPM in Colon Adenocarcinoma.Current medicinal chemistry · 2026Article
- From mono- to multi-cellularFrontiers in cell and developmental biology · 2026Review
- AI-enabled multi-omics integration in colorectal cancer: from molecular stratification to clinical translation.Frontiers in cell and developmental biology · 2026Review
- Alternate actions of CDK4/6 inhibitors beyond cell cycle blockade: unexplored roles in therapy resistance.Cancer metastasis reviews · 2025Review
- Multiscale Construction, Evaluation, and Application of Organoids.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Impact of treatment history on drug resistance of metastatic colorectal cancer organoids.iScience · 2025Article
- Multi-omics strategies for biomarker discovery and application in personalized oncology.Molecular biomedicine · 2025Review
- Integrative RNA-seq analysis reveals immune-related hub genesInternational journal of reproductive biomedicine · 2025Article
- Functional Precision in Pancreatic Cancer: Redefining Biomarkers with Patient-Derived Organoids.International journal of molecular sciences · 2025Review
- The application of organoids in treatment decision-making for digestive system cancers: progress and challenges.Molecular cancer · 2025Review
- Mitochondrial metabolic reprogramming in colorectal cancer: mechanisms of resistance and future clinical interventions.Cell death discovery · 2025Review
- Cancer stem cells: landscape, challenges and emerging therapeutic innovations.Signal transduction and targeted therapy · 2025Review
- TOMM20 as a driver of cancer aggressiveness via oxidative phosphorylation, maintenance of a reduced state, and resistance to apoptosis.Molecular oncology · 2025Article
- Precision medicine research progress based on colorectal cancer organoids.Discover oncology · 2025Review
- Development of CDK4/6 Inhibitors in Gastrointestinal Cancers: Biomarkers to Move Forward.Current issues in molecular biology · 2025Review
Corrections and comments
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Authors and funding
20 authors at 4 institutions in 4 countries.
Funding
Abstract
backgroundPatient-derived organoids (PDOs) from advanced colorectal cancer (CRC) patients could be a key platform to predict drug response and discover new biomarkers. We aimed to integrate PDO drug response with multi-omics characterization beyond genomics.
methodsWe generated 29 PDO lines from 22 advanced CRC patients and provided a morphologic, genomic, and transcriptomic characterization. We performed drug sensitivity assays with a panel of both standard and non-standard agents in five long-term cultures, and integrated drug response with a baseline proteomic and transcriptomic characterization by SWATH-MS and RNA-seq analysis, respectively.
resultsPDOs were successfully generated from heavily pre-treated patients, including a paired model of advanced MSI high CRC deriving from pre- and post-chemotherapy liver metastasis. Our PDOs faithfully reproduced genomic and phenotypic features of original tissue. Drug panel testing identified differential response among PDOs, particularly to oxaliplatin and palbociclib. Proteotranscriptomic analyses revealed that oxaliplatin non-responder PDOs present enrichment of the t-RNA aminoacylation process and showed a shift towards oxidative phosphorylation pathway dependence, while an exceptional response to palbociclib was detected in a PDO with activation of MYC and enrichment of chaperonin T-complex protein Ring Complex (TRiC), involved in proteome integrity. Proteotranscriptomic data fusion confirmed these results within a highly integrated network of functional processes involved in differential response to drugs.
conclusionsOur strategy of integrating PDOs drug sensitivity with SWATH-mass spectrometry and RNA-seq allowed us to identify different baseline proteins and gene expression profiles with the potential to predict treatment response/resistance and to help in the development of effective and personalized cancer therapeutics.
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Registered trials
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.