ArticleNeoplasia (New York, N.Y.)2021
Patient-derived xenograft (PDX) models of colorectal carcinoma (CRC) as a platform for chemosensitivity and biomarker analysis in personalized medicine.
Article in Neoplasia (New York, N.Y.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.
- Clinicopathological characteristics and biomarker alterations in early-onset vs. late-onset colorectal cancer: a systematic review and meta-analysis.International journal of surgery (London, England) · 2026Pooled it
- Comparison of Cell Line-Derived and Patient-Derived Xenograft Technologies in Oncology (Review).Bulletin of experimental biology and medicine · 2026Article
- Construction of 3D bioprinted colorectal cancer models and evaluation of their efficacy and drug sensitivity.APL bioengineering · 2026Article
- Establishment and genomic validation of novel patient-derived xenograft models for drug discovery in gastrointestinal stromal tumor.BMC cancer · 2026Article
- Integration and validation of complementary ex vivo assays for functional precision oncology.NPJ precision oncology · 2026Article
- Translating Pharmacology from Animal Models to Organoids: Advancing Predictive Human Biology in Drug Discovery.Stem cell reviews and reports · 2026Review
- Predicting therapeutic responses in metastatic colorectal cancer through personalized functional profiling of patient-derived spheroids.NPJ precision oncology · 2026Article
- Advancing cancer research: Cutting-edge insights from colorectal cancer patient-derived xenograft mouse models.Genes & diseases · 2026Review
- Informing development of brain cancer therapies within "preclinical trials" using ex vivo patient tumors.Advanced drug delivery reviews · 2026Review
- An Insight into the Emerging Role of Extracellular Vesicle-derived Noncoding RNAs in Colorectal Cancer.MicroRNA (Shariqah, United Arab Emirates) · 2026Review
- Nanomedicine-Based Therapeutic Approaches in Colorectal Cancer Using Patient-Derived Xenograft Models: Prospects and Challenges.International journal of nanomedicine · 2026Review
- From bench to bedside: Advancements in patient-derived xenografts for predicting therapy outcomes in colorectal cancer.World journal of gastroenterology · 2025Review
- Leveraging liquid biopsy to uncover resistance mechanisms and guide personalized immunotherapy.Translational oncology · 2025Review
- PDX models for functional precision oncology and discovery science.Nature reviews. Cancer · 2025Review
- Inhibiting de novo lipogenesis identifies a therapeutic vulnerability in therapy-resistant colorectal cancer.Redox biology · 2025Article
- Recent advances in the development and application of colorectal cancer mouse models.Frontiers in pharmacology · 2025Review
- Approaches to modeling cancer metastasis: from bench to bedside.Frontiers in oncology · 2025Review
- HDACi combination therapy with IDO1i remodels the tumor microenvironment and boosts antitumor efficacy in colorectal cancer with microsatellite stability.Journal of nanobiotechnology · 2024Article
- Integrative ensemble modelling of cetuximab sensitivity in colorectal cancer patient-derived xenografts.Nature communications · 2024Article
- Combined KRAS and TP53 mutation in patients with colorectal cancer enhance chemoresistance to promote postoperative recurrence and metastasis.BMC cancer · 2024Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Patient-derived xenograft (PDX) tumor models represent a valuable platform for identifying new biomarkers and novel targets, to evaluate therapy response and resistance mechanisms. This study aimed at establishment, characterization and therapy testing of colorectal carcinoma-derived PDX. We generated 49 PDX and validated identity between patient tumor and corresponding PDX. Sensitivity of PDX toward conventional and targeted drugs revealed that 92% of PDX responded toward irinotecan, 45% toward 5-FU, 65% toward bevacizumab, and 61% toward cetuximab. Expression of epidermal growth factor receptor (EGFR) ligands correlated to the sensitivity toward cetuximab. Proto-oncogene B-RAF, EGFR, Kirsten rat sarcoma virus oncogene homolog gene copy number correlated positively with cetuximab and erlotinib sensitivity. The mutational analyses revealed an individual mutational profile of PDX and mainly identical profiles of PDX from primary tumor vs corresponding metastasis. Mutation in PIK3CA was a determinant of accelerated tumor doubling time. PDX with wildtype Kirsten rat sarcoma virus oncogene homolog, proto-oncogene B-RAF, and phosphatidylinositol-4,5-bisphosphate 3-kinaseM catalytic subunit alfa showed higher sensitivity toward cetuximab and erlotinib. To study the molecular mechanism of cetuximab resistance, cetuximab resistant PDX models were generated, and changes in HER2, HER3, betacellulin, transforming growth factor alfa were observed. Global proteome and phosphoproteome profiling showed a reduction in canonical EGFR-mediated signaling via PTPN11 (SHP2) and AKT1S1 (PRAS40) and an increase in anti-apoptotic signaling as a consequence of acquired cetuximab resistance. This demonstrates that PDX models provide a multitude of possibilities to identify and validate biomarkers, signaling pathways and resistance mechanisms for clinically relevant improvement in cancer therapy.
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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.