The DOI matches its Crossref record; 26 of the 26 references it cites were found in a registry or an index.
Prognostic and predictive value of common mutations for treatment response and survival in patients with metastatic colorectal cancer
Open accessAbstract
BACKGROUND: We address the prognostic and predictive value of KRAS, PIK3CA and BRAF mutations for clinical outcomes in response to active agents in the treatment of metastatic colorectal cancer (mCRC). METHODS: We determined KRAS, BRAF and PIK3CA mutations in tumours from 168 patients treated for mCRC at two institutions. All patients received 5-FU-based first-line chemotherapy and treatment outcome was analysed retrospectively. RESULTS: KRAS, BRAF and PIK3CA mutations were present in 62 (37%), 13 (8%) and 26 (15%) cases, respectively. Multivariate analysis uncovered BRAF mutation as an independent prognostic factor for decreased survival (hazard ratio (HR) 4.0, 95% confidence interval (CI) 2.1-7.6). In addition, patients with BRAF-mutant tumours had significantly lower progression-free survival (PFS: HR 4.0, 95% CI 2.2-7.4) than those whose tumors that carried wild-type BRAF. Among 92 patients treated using chemotherapy and cetuximab as salvage therapy, KRAS mutation was associated with lack of response (P=0.002) and shorter PFS (P=0.09). BRAF (P=0.0005) and PIK3CA (P=0.01) mutations also predicted reduced PFS in response to cetuximab salvage therapy. CONCLUSIONS: These results underscore the potential of mutational profiling to identify CRCs with different natural histories or treatment responses. The adverse significance of BRAF mutation should inform patient selection and stratification in clinical trials.
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Cites
Bevacizumab plus Irinotecan, Fluorouracil, and Leucovorin for Metastatic Colorectal Cancer
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Mutations of the BRAF gene in human cancer
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Wild-Type KRAS Is Required for Panitumumab Efficacy in Patients With Metastatic Colorectal Cancer
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“Thus, the lack of EGFR mAb response observed in the setting of mutant KRAS (Schubbert et al, 2007; Amado et al, 2008) extends to other common mutations that deregulate cellular signalling pathways, especially BRAF and probably even PIK3CA.”
BackgroundResultInfluentialThe Genomic Landscapes of Human Breast and Colorectal Cancers
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KRAS Mutation Status Is Predictive of Response to Cetuximab Therapy in Colorectal Cancer
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Cited by
De Roock, W., Claes, B., Bernasconi, D., De Schutter, J., Biesmans, B., Fountzilas, G., Kalogeras, K. T., Kotoula, V., Papamichael, D., Laurent-Puig, P., et al. (2010) · The Lancet Oncology · doi:10.1016/s1470-2045(10)70130-3 · Cited by 2,144
Van Cutsem, E., Köhne, C.-H., Láng, I., Folprecht, G., Nowacki, M. P., Cascinu, S., Shchepotin, I., Maurel, J., Cunningham, D., Tejpar, S., et al. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2010.33.5091 · Cited by 1,882
Resistance to anti-EGFR therapy in colorectal cancer: From heterogeneity to convergent evolution
Misale, S., Di Nicolantonio, F., Sartore-Bianchi, A., Siena, S., & Bardelli, A. (2014) · Cancer Discovery · doi:10.1158/2159-8290.cd-14-0462 · Cited by 513
Pietrantonio, F., Petrelli, F., Coinu, A., Di Bartolomeo, M., Borgonovo, K., Maggi, C., Cabiddu, M., Iacovelli, R., Bossi, I., Lonati, V., et al. (2015) · European Journal of Cancer · doi:10.1016/j.ejca.2015.01.054 · Cited by 486
Siena, S., Sartore-Bianchi, A., Di Nicolantonio, F., Balfour, J., & Bardelli, A. (2009) · JNCI: Journal of the National Cancer Institute · doi:10.1093/jnci/djp280 · Cited by 429
Metadata
- Authors
- Souglakos, J., Philips, J., Wang, R., Marwah, S., Silver, M., Tzardi, M., Silver, J., Ogino, S., Hooshmand, S., Kwak, E., Freed, E., Meyerhardt, J. A., Saridaki, Z., Georgoulias, V, Finkelstein, D., Fuchs, C. S., Kulke, M. H., & Shivdasani, R. A.
- Venue
- British Journal of Cancer
- Published
- 2009-07-14
- Volume
- 101
- Issue
- 3
- Pages
- 465-472
- ISSN
- 0007-0920 (ISSN-L)
- 1532-1827
- OpenAlex
- W1969730641
- Cited by
- 310
- References
- 26
- FWCI
- 15.22
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Souglakos, J., Philips, J., Wang, R., Marwah, S., Silver, M., Tzardi, M., Silver, J., Ogino, S., Hooshmand, S., Kwak, E., Freed, E., Meyerhardt, J. A., Saridaki, Z., Georgoulias, V, Finkelstein, D., Fuchs, C. S., Kulke, M. H., & Shivdasani, R. A. (2009). Prognostic and predictive value of common mutations for treatment response and survival in patients with metastatic colorectal cancer. British Journal of Cancer. https://doi.org/10.1038/sj.bjc.6605164
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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.
