The DOI matches its Crossref record; 31 of the 31 references it cites were found in a registry or an index.
Molecular Correlates of Imatinib Resistance in Gastrointestinal Stromal Tumors
Abstract
Purpose: Gastrointestinal stromal tumors (GISTs) commonly harbor oncogenic mutations of the KIT or platelet-derived growth factor alpha (PDGFRA) kinases, which are targets for imatinib. In clinical studies, 75% to 90% of patients with advanced GISTs experience clinical benefit from imatinib. However, imatinib resistance is an increasing clinical problem. Patients and Methods: One hundred forty-seven patients with advanced, unresectable GISTs were enrolled onto a randomized, phase II clinical study of imatinib. Specimens from pretreatment and/or imatinib-resistant tumors were analyzed to identify molecular correlates of imatinib resistance. Secondary kinase mutations of KIT or PDGFRA that were identified in imatinib-resistant GISTs were biochemically profiled for imatinib sensitivity. Results: Molecular studies were performed using specimens from 10 patients with primary and 33 patients with secondary resistance. Imatinib-resistant tumors had levels of activated KIT that were similar to or greater than those typically found in untreated GISTs. Secondary kinase mutations were rare in GISTs with primary resistance but frequently found in GISTs with secondary resistance (10% v 67%; P = .002). Evidence for clonal evolution and/or polyclonal secondary kinase mutations was seen in three (18.8%) of 16 patients. Secondary kinase mutations were nonrandomly distributed and were associated with decreased imatinib sensitivity compared with typical KIT exon 11 mutations. Using RNAi technology, we demonstrated that imatinib-resistant GIST cells remain dependent on KIT kinase activity for activation of critical downstream signaling pathways. Conclusion: Different molecular mechanisms are responsible for primary and secondary imatinib resistance in GISTs. These findings have implications for future approaches to the growing problem of imatinib resistance in patients with advanced GISTs.
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Cites
Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors
Demetri, G. D., von Mehren, M., Blanke, C. D., Van den Abbeele, A. D., Eisenberg, B., Roberts, P. J., Heinrich, M. C., Tuveson, D. A., Singer, S., Janicek, M., et al. (2002) · New England Journal of Medicine · doi:10.1056/nejmoa020461 · Cited by 4,389
Self-citationPDGFRA Activating Mutations in Gastrointestinal Stromal Tumors
Heinrich, M. C., Corless, C. L., Duensing, A., McGreevey, L., Chen, C.-J., Joseph, N., Singer, S., Griffith, D. J., Haley, A., Town, A., et al. (2003) · Science · doi:10.1126/science.1079666 · Cited by 2,301
Self-citationKinase Mutations and Imatinib Response in Patients With Metastatic Gastrointestinal Stromal Tumor
Heinrich, M. C., Corless, C. L., Demetri, G. D., Blanke, C. D., von Mehren, M., Joensuu, H., McGreevey, L. S., Chen, C.-J., Van den Abbeele, A. D., Druker, B. J., et al. (2003) · Journal of Clinical Oncology · doi:10.1200/jco.2003.04.190 · Cited by 2,299
Self-citationJoensuu, H., Roberts, P. J., Sarlomo-Rikala, M., Andersson, L. C., Tervahartiala, P., Tuveson, D., Silberman, S. L., Capdeville, R., Dimitrijevic, S., Druker, B., et al. (2001) · New England Journal of Medicine · doi:10.1056/nejm200104053441404 · Cited by 2,037
Self-citationVerweij, J., Casali, P. G., Zalcberg, J., LeCesne, A., Reichardt, P., Blay, J.-Y., Issels, R., van Oosterom, A., Hogendoorn, P. C., Van Glabbeke, M., et al. (2004) · The Lancet · doi:10.1016/s0140-6736(04)17098-0 · Cited by 1,665
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Biology of Gastrointestinal Stromal Tumors
Corless, C. L., Fletcher, J. A., & Heinrich, M. C. (2004) · Journal of Clinical Oncology · doi:10.1200/jco.2004.05.140 · Cited by 1,224
Self-citationKIT activation is a ubiquitous feature of gastrointestinal stromal tumors.
Rubin, B. P., Singer, S., Tsao, C., Duensing, A. U., Lux, M. L., Ruiz, R., Hibbard, M. K., Chen, C. J., Xiao, S., Tuveson, D. A., et al. (2001) · PubMed · Cited by 959
Self-citationCorless, C. L., Schroeder, A., Griffith, D., Town, A., McGreevey, L., Harrell, P., Shiraga, S., Bainbridge, T., Morich, J., & Heinrich, M. C. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2005.14.068 · Cited by 849
Self-citationAntonescu, C. R., Besmer, P., Guo, T., Arkun, K., Hom, G., Koryotowski, B., Leversha, M. A., Jeffrey, P. D., Desantis, D., Singer, S., et al. (2005) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-04-2245 · Cited by 836
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MET Amplification Leads to Gefitinib Resistance in Lung Cancer by Activating ERBB3 Signaling
Engelman, J. A., Zejnullahu, K., Mitsudomi, T., Song, Y., Hyland, C., Park, J. O., Lindeman, N., Gale, C.-M., Zhao, X., Christensen, J., et al. (2007) · Science · doi:10.1126/science.1141478 · Cited by 4,496
COT drives resistance to RAF inhibition through MAP kinase pathway reactivation
Johannessen, C. M., Boehm, J. S., Kim, S. Y., Thomas, S. R., Wardwell, L., Johnson, L. A., Emery, C. M., Stransky, N., Cogdill, A. P., Barretina, J., et al. (2010) · Nature · doi:10.1038/nature09627 · Cited by 1,460
Kinase-targeted cancer therapies: progress, challenges and future directions
Bhullar, K. S., Lagarón, N. O., McGowan, E. M., Parmar, I., Jha, A., Hubbard, B. P., & Rupasinghe, H. P. V. (2018) · Molecular Cancer · doi:10.1186/s12943-018-0804-2 · Cited by 1,245
Gastrointestinal stromal tumour
Rubin, B. P., Heinrich, M. C., & Corless, C. L. (2007) · The Lancet · doi:10.1016/s0140-6736(07)60780-6 · Cited by 1,036
Self-citationHigh-throughput oncogene mutation profiling in human cancer
Thomas, R. K., Baker, A. C., DeBiasi, R. M., Winckler, W., LaFramboise, T., Lin, W. M., Wang, M., Feng, W., Zander, T., MacConaill, L. E., et al. (2007) · Nature Genetics · doi:10.1038/ng1975 · Cited by 988
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Metadata
- Authors
- Heinrich, M. C., Corless, C. L., Blanke, C. D., Demetri, G. D., Joensuu, H., Roberts, P. J., Eisenberg, B. L., von Mehren, M., Fletcher, C. D. M., Sandau, K., McDougall, K., Ou, W.-B., Chen, C.-J., & Fletcher, J. A.
- Venue
- Journal of Clinical Oncology
- Published
- 2006-10-10
- Volume
- 24
- Issue
- 29
- Pages
- 4764-4774
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- OpenAlex
- W2103304755
- Cited by
- 814
- References
- 31
- FWCI
- 44.54
- Type
- journal article
- Language
- en
- Open access
- closed
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- Heinrich, M. C., Corless, C. L., Blanke, C. D., Demetri, G. D., Joensuu, H., Roberts, P. J., Eisenberg, B. L., von Mehren, M., Fletcher, C. D. M., Sandau, K., McDougall, K., Ou, W.-B., Chen, C.-J., & Fletcher, J. A. (2006). Molecular Correlates of Imatinib Resistance in Gastrointestinal Stromal Tumors. Journal of Clinical Oncology. https://doi.org/10.1200/jco.2006.06.2265
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