The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.
Digital karyotyping identifies thymidylate synthase amplification as a mechanism of resistance to 5-fluorouracil in metastatic colorectal cancer patients
Open accessAbstract
Resistance to chemotherapy is a major cause of mortality in advanced cancer patients. In this study, digital karyotyping was used to search for genomic alterations in liver metastases that were clinically resistant to 5-fluorouracil (5-FU). In two of four patients, we identified amplification of an ≈100-kb region on 18p11.32 that was of particular interest because it contained the gene encoding thymidylate synthase (TYMS), a molecular target of 5-FU. Analysis of TYMS by fluorescence in situ hybridization identified TYMS gene amplification in 23% of 31 5-FU-treated cancers, whereas no amplification was observed in metastases of patients that had not been treated with 5-FU. Patients with metastases containing TYMS amplification had a substantially shorter median survival (329 days) than those without amplification (1,021 days, P <0.01). These data suggest that genetic amplification of TYMS is a major mechanism of 5-FU resistance in vivo and have important implications for the management of colorectal cancer patients with recurrent disease.
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5-Fluorouracil: mechanisms of action and clinical strategies
Longley, D. B., Harkin, D. P., & Johnston, P. G. (2003) · Nature Reviews Cancer · doi:10.1038/nrc1074 · Cited by 5,332
Clinical Resistance to STI-571 Cancer Therapy Caused by BCR-ABL Gene Mutation or Amplification
Gorre, M. E., Mohammed, M., Ellwood, K., Hsu, N., Paquette, R., Rao, P. N., & Sawyers, C. L. (2001) · Science · doi:10.1126/science.1062538 · Cited by 3,104
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Self-citationLiquid Biopsies: Genotyping Circulating Tumor DNA
Diaz, L. A., & Bardelli, A. (2014) · Journal of Clinical Oncology · doi:10.1200/jco.2012.45.2011 · Cited by 2,210
Self-citation5-fluorouracil and other fluoropyrimidines in colorectal cancer: Past, present and future
Vodenkova, S., Buchler, T., Cervena, K., Veskrnova, V., Vodicka, P., & Vymetalkova, V. (2020) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2019.107447 · Cited by 956
Sun, Y., Campisi, J., Higano, C., Beer, T. M., Porter, P., Coleman, I., True, L., & Nelson, P. S. (2012) · Nature Medicine · doi:10.1038/nm.2890 · Cited by 793
“Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas. Nature 445, 656–660 (2007). 36.”
BackgroundInfluentialResistance to cancer chemotherapy: failure in drug response from ADME to P-gp
Alfarouk, K. O., Stock, C.-M., Taylor, S., Walsh, M., Muddathir, A. K., Verduzco, D., Bashir, A. H. H., Mohammed, O. Y., Elhassan, G. O., Harguindey, S., et al. (2015) · Cancer Cell International · doi:10.1186/s12935-015-0221-1 · Cited by 665
Metadata
- Authors
- Wang, T.-L., Diaz, L. A., Romans, K., Bardelli, A., Saha, S., Galizia, G., Choti, M., Donehower, R., Parmigiani, G., Shih, I.-M., Iacobuzio-Donahue, C., Kinzler, K. W., Vogelstein, B., Lengauer, C., & Velculescu, V. E.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2004-02-17
- Volume
- 101
- Issue
- 9
- Pages
- 3089-3094
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2023389182
- Cited by
- 183
- References
- 2
- FWCI
- 7.64
- Type
- journal article
- Language
- en
- Open access
- green
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- CoChat. (2026). Citation check: Digital karyotyping identifies thymidylate synthase amplification as a mechanism of resistance to 5-fluorouracil in metastatic colorectal cancer patients. https://app.cochat.ai/papers/10.1073/pnas.0308716101
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- Wang, T.-L., Diaz, L. A., Romans, K., Bardelli, A., Saha, S., Galizia, G., Choti, M., Donehower, R., Parmigiani, G., Shih, I.-M., Iacobuzio-Donahue, C., Kinzler, K. W., Vogelstein, B., Lengauer, C., & Velculescu, V. E. (2004). Digital karyotyping identifies thymidylate synthase amplification as a mechanism of resistance to 5-fluorouracil in metastatic colorectal cancer patients. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0308716101
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
