The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.
Dabrafenib; Preclinical Characterization, Increased Efficacy when Combined with Trametinib, while BRAF/MEK Tool Combination Reduced Skin Lesions
Open accessAbstract
Mitogen-Activated Protein Kinase (MAPK) pathway activation has been implicated in many types of human cancer. BRAF mutations that constitutively activate MAPK signalling and bypass the need for upstream stimuli occur with high prevalence in melanoma, colorectal carcinoma, ovarian cancer, papillary thyroid carcinoma, and cholangiocarcinoma. In this report we characterize the novel, potent, and selective BRAF inhibitor, dabrafenib (GSK2118436). Cellular inhibition of BRAF(V600E) kinase activity by dabrafenib resulted in decreased MEK and ERK phosphorylation and inhibition of cell proliferation through an initial G1 cell cycle arrest, followed by cell death. In a BRAF(V600E)-containing xenograft model of human melanoma, orally administered dabrafenib inhibited ERK activation, downregulated Ki67, and upregulated p27, leading to tumor growth inhibition. However, as reported for other BRAF inhibitors, dabrafenib also induced MAPK pathway activation in wild-type BRAF cells through CRAF (RAF1) signalling, potentially explaining the squamous cell carcinomas and keratoacanthomas arising in patients treated with BRAF inhibitors. In addressing this issue, we showed that concomitant administration of BRAF and MEK inhibitors abrogated paradoxical BRAF inhibitor-induced MAPK signalling in cells, reduced the occurrence of skin lesions in rats, and enhanced the inhibition of human tumor xenograft growth in mouse models. Taken together, our findings offer preclinical proof of concept for dabrafenib as a specific and highly efficacious BRAF inhibitor and provide evidence for its potential clinical benefits when used in combination with a MEK inhibitor.
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Mutations of the BRAF gene in human cancer
Davies, H., Bignell, G. R., Cox, C., Stephens, P., Edkins, S., Clegg, S., Teague, J., Woffendin, H., Garnett, M. J., Bottomley, W., et al. (2002) · Nature · doi:10.1038/nature00766 · Cited by 10,674
Improved survival with vemurafenib in melanoma with BRAF V600E mutation
Chapman, P. B., Hauschild, A., Robert, C., Haanen, J. B., Ascierto, P., Larkin, J., Dummer, R., Garbe, C., Testori, A., Maio, M., et al. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1103782 · Cited by 7,720
MAP kinase signalling pathways in cancer
Dhillon, A. S., Hagan, S., Rath, O., & Kolch, W. (2007) · Oncogene · doi:10.1038/sj.onc.1210421 · Cited by 2,995
Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations
Flaherty, K. T., Infante, J. R., Daud, A., Gonzalez, R., Kefford, R. F., Sosman, J., Hamid, O., Schuchter, L., Cebon, J., Ibrahim, N., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1210093 · Cited by 2,810
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
RAF inhibitor resistance is mediated by dimerization of aberrantly spliced BRAF(V600E)
Poulikakos, P. I., Persaud, Y., Janakiraman, M., Kong, X., Ng, C., Moriceau, G., Shi, H., Atefi, M., Titz, B., Gabay, M. T., et al. (2011) · Nature · doi:10.1038/nature10662 · Cited by 1,454
Cited by
Targeted protein degradation by PROTACs
Neklesa, T. K., Winkler, J. D., & Crews, C. M. (2017) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2017.02.027 · Cited by 599
Planchard, D., Kim, T. M., Mazieres, J., Quoix, E., Riely, G., Barlesi, F., Souquet, P.-J., Smit, E. F., Groen, H. J. M., Kelly, R. J., et al. (2016) · The Lancet Oncology · doi:10.1016/s1470-2045(16)00077-2 · Cited by 453
Ten things you should know about protein kinases: IUPHAR R eview 14
Fabbro, D., Cowan‐Jacob, S. W., & Moebitz, H. (2015) · British Journal of Pharmacology · doi:10.1111/bph.13096 · Cited by 347
Dabrafenib plus trametinib in BRAFV600E-mutated rare cancers: the phase 2 ROAR trial
Subbiah, V., Kreitman, R. J., Wainberg, Z. A., Gazzah, A., Lassen, U., Stein, A., Wen, P. Y., Dietrich, S., de Jonge, M. J. A., Blay, J.-Y., et al. (2023) · Nature Medicine · doi:10.1038/s41591-023-02321-8 · Cited by 343
Ribas, A., Gonzalez, R., Pavlick, A., Hamid, O., Gajewski, T. F., Daud, A., Flaherty, L., Logan, T., Chmielowski, B., Lewis, K., et al. (2014) · The Lancet Oncology · doi:10.1016/s1470-2045(14)70301-8 · Cited by 299
Metadata
- Authors
- King, A. J., Arnone, M. R., Bleam, M. R., Moss, K. G., Yang, J., Fedorowicz, K. E., Smitheman, K. N., Erhardt, J. A., Hughes-Earle, A., Kane-Carson, L. S., Sinnamon, R. H., Qi, H., Rheault, T. R., Uehling, D. E., & Laquerre, S. G.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2013-07-03
- Volume
- 8
- Issue
- 7
- Pages
- e67583
- ISSN
- 1932-6203 (ISSN-L)
- OpenAlex
- W2162044478
- Cited by
- 221
- References
- 6
- FWCI
- 7.13
- Type
- journal article
- Language
- en
- Open access
- gold
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- King, A. J., Arnone, M. R., Bleam, M. R., Moss, K. G., Yang, J., Fedorowicz, K. E., Smitheman, K. N., Erhardt, J. A., Hughes-Earle, A., Kane-Carson, L. S., Sinnamon, R. H., Qi, H., Rheault, T. R., Uehling, D. E., & Laquerre, S. G. (2013). Dabrafenib; Preclinical Characterization, Increased Efficacy when Combined with Trametinib, while BRAF/MEK Tool Combination Reduced Skin Lesions. PLoS ONE. https://doi.org/10.1371/journal.pone.0067583
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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