ArticlePloS one2017
In vivo and ex vivo cetuximab sensitivity assay using three-dimensional primary culture system to stratify KRAS mutant colorectal cancer.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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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
18 citing papers in PubMed, 34 citations in OpenAlex.
- Clinical significance of non-invasive in vitro drug sensitivity profiling using pancreatic cancer organoids derived from saline flushes collected during routine EUS-FNA.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Article
- Cetuximab increases LGR5 expression and augments LGR5-targeting antibody-drug conjugate efficacy in patient-derived colorectal cancer models.Cell reports. Medicine · 2025Article
- Cetuximab increases LGR5 expression and augments LGR5-targeting antibody-drug conjugate efficacy in patient-derived colorectal cancer models.bioRxiv : the preprint server for biology · 2025Article
- The law of diminishing marginal returns in health insurance: evidence on child health outcomes from Pakistan's Sehat Sahulat program.Frontiers in public health · 2025Article
- Growth pattern of de novo small clusters of colorectal cancer is regulated by Notch signaling at detachment.Cancer science · 2024Article
- Inhibition of the bone morphogenetic protein pathway suppresses tumor growth through downregulation of epidermal growth factor receptor in MEK/ERK-dependent colorectal cancer.Cancer science · 2023Article
- Article
- Ex vivo chemosensitivity assay using primary ovarian cancer organoids for predicting clinical response and screening effective drugs.Human cell · 2023Article
- Anti-cancer effect of afatinib, dual inhibitor of HER2 and EGFR, on novel mutation HER2 E401G in models of patient-derived cancer.BMC cancer · 2023Article
- Reconstructing the tumor architecture into organoids.Advanced drug delivery reviews · 2021Review
- Organoid: Next-Generation Modeling of Cancer Research and Drug Development.Frontiers in oncology · 2021Review
- Patient-Derived Organoids in Precision Medicine: Drug Screening, Organoid-on-a-Chip and Living Organoid Biobank.Frontiers in oncology · 2021Review
- Human Tumor-Derived Matrix Improves the Predictability of Head and Neck Cancer Drug Testing.Cancers · 2019Article
- Ex vivo tissue slice culture system to measure drug-response rates of hepatic metastatic colorectal cancer.BMC cancer · 2019Article
- Effects of culture method on response to EGFR therapy in head and neck squamous cell carcinoma cells.Scientific reports · 2019Article
- Review
- High-throughput screening in colorectal cancer tissue-originated spheroids.Cancer science · 2019Article
- RAS nucleotide cycling underlies the SHP2 phosphatase dependence of mutant BRAF-, NF1- and RAS-driven cancers.Nature cell biology · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In clinic, cetuximab, an anti-EGFR antibody, improves treatment outcomes in colorectal cancer (CRC). KRAS-mutant CRC is generally resistant to cetuximab, although difference of the sensitivity among KRAS-mutants has not been studied in detail. We previously developed the cancer tissue-originated spheroid (CTOS) method, a primary culture method for cancer cells. We applied CTOS method to investigate whether ex vivo cetuximab sensitivity assays reflect the difference in sensitivity in the xenografts. Firstly, in vivo cetuximab treatment was performed with xenografts derived from 10 CTOS lines (3 KRAS-wildtype and 7 KRAS mutants). All two CTOS lines which exhibited tumor regression were KRAS-wildtype, meanwhile all KRAS-mutant CTOS lines grew more than the initial size: were resistant to cetuximab according to the clinical evaluation criteria, although the sensitivity was quite diverse. We divided KRAS-mutants into two groups; partially responsive group in which cetuximab had a substantial growth inhibitory effect, and resistant group which exhibited no effect. The ex vivo signaling assay with EGF stimulation revealed that the partially responsive group, but not the resistant group, exhibited suppressed ERK phosphorylation ex vivo. Furthermore, two lines from the partially responsive group, but none of the lines in the resistant group, exhibited a combinatory effect of cetuximab and trametinib, a MEK inhibitor, ex vivo and in vivo. Taken together, the results indicate that ex vivo signaling assay reflects the difference in sensitivity in vivo and stratifies KRAS mutant CTOS lines by sensitivity. Therefore, coupling the in vivo and ex vivo assays with CTOS can be a useful platform for understanding the mechanism of diversity in drug sensitivity.
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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.