The DOI matches its Crossref record; 26 of the 27 references it cites were found in a registry or an index.
MAP Kinase Pathway Alterations in BRAF -Mutant Melanoma Patients with Acquired Resistance to Combined RAF/MEK Inhibition
Open accessPublished version of a preprint
Abstract
Treatment of BRAF-mutant melanoma with combined dabrafenib and trametinib, which target RAF and the downstream MAP–ERK kinase (MEK)1 and MEK2 kinases, respectively, improves progression-free survival and response rates compared with dabrafenib monotherapy. Mechanisms of clinical resistance to combined RAF/MEK inhibition are unknown. We performed whole-exome sequencing (WES) and whole-transcriptome sequencing (RNA-seq) on pretreatment and drug-resistant tumors from five patients with acquired resistance to dabrafenib/trametinib. In three of these patients, we identified additional mitogen-activated protein kinase (MAPK) pathway alterations in the resistant tumor that were not detected in the pretreatment tumor, including a novel activating mutation in MEK2 (MEK2Q60P). MEK2Q60P conferred resistance to combined RAF/MEK inhibition in vitro, but remained sensitive to inhibition of the downstream kinase extracellular signal–regulated kinase (ERK). The continued MAPK signaling-based resistance identified in these patients suggests that alternative dosing of current agents, more potent RAF/MEK inhibitors, and/or inhibition of the downstream kinase ERK may be needed for durable control of BRAF-mutant melanoma. Significance: This study represents an initial clinical genomic study of acquired resistance to combined RAF/MEK inhibition in BRAF-mutant melanoma, using WES and RNA-seq. The presence of diverse resistance mechanisms suggests that serial biopsies and genomic/molecular profiling at the time of resistance may ultimately improve the care of patients with resistant BRAF-mutant melanoma by specifying tailored targeted combinations to overcome specific resistance mechanisms. Cancer Discov; 4(1); 61–8. ©2013 AACR. See related commentary by Solit and Rosen, p. 27 This article is highlighted in the In This Issue feature, p. 1
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Nonetheless, resistance is pervasive, and observations so far let us conclude that, in most cases, progression to alternative strategies of drug elusion will inevitably occur [109, 140].”
From Primary and acquired resistance to EGFR-targeted therapies in colorectal cancer: impact on future treatment strategies (2014) · cites this paper as [140]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1)
Eisenhauer, E. A., Therasse, P., Bogaerts, J., Schwartz, L. H., Sargent, D., Ford, R., Dancey, J., Arbuck, S., Gwyther, S., Mooney, M., et al. (2009) · European Journal of Cancer · doi:10.1016/j.ejca.2008.10.026 · Cited by 29,534
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
Self-citationInhibition of Mutated, Activated BRAF in Metastatic Melanoma
Flaherty, K. T., Puzanov, I., Kim, K. B., Ribas, A., McArthur, G. A., Sosman, J. A., O'Dwyer, P. J., Lee, R. J., Grippo, J. F., Nolop, K., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa1002011 · Cited by 3,103
Self-citationCombined 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
Self-citationMelanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation
Nazarian, R., Shi, H., Wang, Q., Kong, X., Koya, R. C., Lee, H., Chen, Z., Lee, M., Attar, N., Sazegar, H., et al. (2010) · Nature · doi:10.1038/nature09626 · Cited by 2,244
Improved Survival with MEK Inhibition in BRAF-Mutated Melanoma
Flaherty, K. T., Robert, C., Hersey, P., Nathan, P., Garbe, C., Milhem, M. M., Демидов, Л. В., Hassel, J. C., Rutkowski, P. L., Mohr, P., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1203421 · Cited by 2,205
Self-citationSurvival in BRAF V600-mutant advanced melanoma treated with vemurafenib
Sosman, J. A., Kim, K. B., Schuchter, L., Gonzalez, R., Pavlick, A. C., Weber, J. S., McArthur, G. A., Hutson, T. E., Moschos, S. J., Flaherty, K. T., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1112302 · Cited by 2,156
Self-citationTumour micro-environment elicits innate resistance to RAF inhibitors through HGF secretion
Straussman, R., Morikawa, T., Shee, K., Barzily-Rokni, M., Qian, Z. R., Du, J., Davis, A., Mongare, M. M., Gould, J., Frederick, D. T., et al. (2012) · Nature · doi:10.1038/nature11183 · Cited by 1,771
Self-citationCOT 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
Self-citationRAF 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
Self-citation
Flagged first, then by citations
1 of the 27 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Items 401–481 of 481
Gorlov, I., Amos, C. I., Tsavachidis, S., Begg, C. B., Hernando, E., Cheng, C., Shen, R., Orlow, I., Luo, L., Ernstoff, M. S., et al. (2020) · Human Mutation · doi:10.1002/humu.24078 · Cited by 3
Lopes, B. A., Ortelan, A. G., Faria, A. V. D. S., & Ferreira‐Halder, C. V. (2020) · Brazilian Journal of Health Review · doi:10.34119/bjhrv3n4-291 · Cited by 4
Dermatologic adverse events associated with targeted therapies for melanoma
Scarpato, L., Festino, L., Vanella, V., Madonna, G., Mastroianni, M., Palla, M., & Ascierto, P. A. (2021) · Expert Opinion on Drug Safety · doi:10.1080/14740338.2022.1986000 · Cited by 3
Targeted therapy of anaplastic thyroid cancer
Алексеевич, Н. П., Polyakov, A. P., Sleptsov, I. V., Boyko, N. S., Gronskaya, Y. A. G., Timofeeva, N. I., & Chernikov, R. A. (2022) · Head and neck tumors (HNT) · doi:10.17650/2222-1468-2022-12-4-33-38 · Cited by 3
Revisiting the Role of B-RAF Kinase as a Therapeutic Target in Melanoma
Kozyra, P., & Pitucha, M. (2023) · Current Medicinal Chemistry · doi:10.2174/0109298673258495231011065225 · Cited by 4
Activating mutations drive human MEK1 kinase using a gear-shifting mechanism
Patil, K., Wang, Y., Chen, Z., Suresh, K., & Radhakrishnan, R. (2023) · Biochemical Journal · doi:10.1042/bcj20230281 · Cited by 4
Existence, stability, and numerical simulation of a nonlinear brain tumor model
Afshari, H., Kalantari, S., Anvari, M., & Marasi, H. R. (2025) · Journal of Inequalities and Applications · doi:10.1186/s13660-025-03276-9 · Cited by 3
Oncogene-Directed Small Molecule Inhibitors for the Treatment of Cutaneous Melanoma
Eliades, P. J., Flaherty, K. T., & Tsao, H. (2015) · Melanoma Management · doi:10.2217/mmt.15.5 · Cited by 3
Self-citationDecker, M., Huang, B. J., Ware, T. B., Boone, C. D., Tang, M., Ybarra, J., Sale, M. J., Francois, R. A., Ballapuram, A. C., Taran, K. A., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.03.20.644389 · Cited by 3
Knoedler, L., Huelsboemer, L. F., Hollmann, K., Alfertshofer, M. G., Herfeld, K., Hosseini, H. C., Boroumand, S., Stögner, V. A., Safi, A., Perl, M., et al. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1276306 · Cited by 3
dos Santos, G. A., Castro, J. P., Guardia, G. D. A., dos Santos, F. F., Birbrair, A., & Galante, P. A. F. (2026) · Aging Cell · doi:10.1111/acel.70696 · Cited by 3
Németh, A., Bányai, G. L., Dobos, N. K., Kós, T., Gaál, A., Varga, Z., Buzás, E. I., Khamari, D., Dank, M., Takács, I., et al. (2024) · Cell Communication and Signaling · doi:10.1186/s12964-024-01660-4 · Cited by 2
Current and emerging treatment options for BRAFV600-mutant melanoma
Javaid, A., Peres, T., Pozas, J., Thomas, J. M., & Larkin, J. (2025) · Expert Review of Anticancer Therapy · doi:10.1080/14737140.2025.2451722 · Cited by 3
Fischer, G. M., Fang, R., Xu, S., Karkempetzaki, A. I., Migayron, L., Draper, E. C., Wang, J., Schatton, T., Mandinova, A., Murphy, G. F., et al. (2025) · British Journal of Dermatology · doi:10.1093/bjd/ljaf378 · Cited by 2
Patient-Derived Xenografting of Human Melanoma
Boyle, S. E., Fedele, C. G., & Shackleton, M. J. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-804010-2.00023-0 · Cited by 2
Mardis, E. R. (2015) · F1000Research · doi:10.12688/f1000research.6645.1 · Cited by 2
The Potential Complementary Role of Targeted Alpha Therapy in the Management of Metastatic Melanoma
Brown, M. P., Bezak, E., & Allen, B. (2015) · Melanoma Management · doi:10.2217/mmt.15.26 · Cited by 2
New Challenges in Cancer Therapy: MAPK Inhibitors from Bench to Bedside
Ropert, C., & Huth, H. W. (2017) · Springer eBooks · doi:10.1007/978-3-319-53082-6_3 · Cited by 1
CRISPR Screens Identify Essential Cell Growth Mediators in BRAF-inhibitor Resistant MelanomaPreprint
Li, Z., Wang, B., Gu, S., Jiang, P., Sahu, A., Chen, C.-H., Han, T., Shi, S., Wang, X., Traugh, N., et al. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2019.12.16.876631 · Cited by 2
Puniya, B. L., Allen, L., Hochfelder, C. G., Majumder, M., & Helikar, T. (2016) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2016.00010 · Cited by 1
Tridente, G. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-809400-6.00024-x · Cited by 1
Treating Metastatic Melanoma in 2014: What Just Happened and What Is Next?
Chapman, P. B. (2014) · American Society of Clinical Oncology Educational Book · doi:10.14694/edbook_am.2014.34.16 · Cited by 2
Resistance to MAPK inhibition: come see(c) AMP ed up melanoma
Rodríguez, C. I., & Setaluri, V. (2014) · Pigment Cell & Melanoma Research · doi:10.1111/pcmr.12230 · Cited by 1
Mutation Yield of a 34-Gene Solid Tumor Panel in Community-Based Tumor Samples
Sanders, H. R., Qu, K. Z., Li, H., Ma, L., Barlan, C., Zhang, X., Prentice, J., Wolfson, D., Crossley, B., Sferruzza, A. D., et al. (2016) · Molecular Diagnosis & Therapy · doi:10.1007/s40291-016-0197-0 · Cited by 1
Idris, O. A., Shebrain, A., Jawad, A., Pacione, S. C., Haj, D., Bzizi, H. F., Ahmedfiqi, Y. O., Jahromi, B. S., Deleon, N., Zhang, T., et al. (2025) · Clinical Surgical Oncology · doi:10.1016/j.cson.2025.100095 · Cited by 1
Molecular Genetics of Melanocytic Neoplasia
Hodis, E., & Garraway, L. A. (2017) · Springer eBooks · doi:10.1007/978-1-4614-7322-0_29-1 · Cited by 1
Self-citationTridente, G. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-809400-6.00023-8 · Cited by 1
Molecular Genetics of Melanocytic Neoplasia
Hodis, E., & Garraway, L. A. (2019) · Springer eBooks · doi:10.1007/978-1-4614-7147-9_29 · Cited by 1
Self-citationKorkut, A., Wang, W., Demir, E., Aksoy, B. A., Jing, X., Molinelli, E. J., Babur, Ö., Bemis, D. L., Solit, D. B., Pratilas, C. A., et al. (2014) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/008201 · Cited by 1
Decoding molecular programs in melanoma brain metastasesPreprint
Radke, J., Schumann, E., Onken, J., Koll, R., Acker, G., Bodnar, B., Senger, C., Tierling, S., Möbs, M., Vajkoczy, P., et al. (2022) · medRxiv · doi:10.1101/2022.02.06.22270509 · Cited by 1
Hedberg, M. L. (2015) · D-Scholarship@Pitt (University of Pittsburgh)
4th international conference on tumor progression and therapeutic resistance: meeting report
Prabhu, V. V., & El‐Deiry, W. S. (2015) · Cancer Biology & Therapy · doi:10.1080/15384047.2015.1004928 · Cited by 1
Studies of overcoming acquired resistance : molecular mechanisms and development of novel drugs
Wang, X. (2014) · Figshare
The role of Axl in melanoma metastasis
Kang, J. (2015) · NORA - Norwegian Open Research Archives
Inhibition of BRAF and MEK in BRAF-mutant melanoma
Coleman, R. E., & Hadji, P. (2015)
Clinical Approach to Advanced Melanoma for Today and Tomorrow
Monterroso, J., Ji, Y., Emmons, S., & Verschraegen, C. F. (2015) · Springer eBooks · doi:10.1007/978-3-319-21683-6_28
Understanding the Genetic Mechanisms of Cancer Drug Resistance Using Genomic
Hu, A., & Zhang, Z. (2016)
Local IL-15-immunotherapy to treat melanoma
Hanes, M. R. (2017) · DalSpace (Dalhousie University)
Improving the Delivery of Molecularly-Targeted Agents to Effectively Treat Melanoma Brain Metastases
Vaidhyanathan, S. (2015) · University of Minnesota Digital Conservancy (University of Minnesota)
Translational Research and Genomics Driven Trials in Thyroid Cancer
Cabanillas, M. E., Schweppe, R. E., Dadu, R., Cote, G. J., Beadnell, T. C., & Hofmann, M.-C. C. (2018) · Springer eBooks · doi:10.1007/978-3-319-91725-2_24
Meierjohann, S., & Schilling, B. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-811785-9.00046-6
Sun, X. (2019) · IntechOpen eBooks · doi:10.5772/intechopen.76185
Targeted Therapies for BRAF-Mutant Metastatic Melanoma
Johnson, D. B., Dummer, R., Flaherty, K. T., & Smalley, K. S. M. (2018) · Springer eBooks · doi:10.1007/978-3-319-46029-1_40-1
Self-citationGillis, N. (2019) · Carolina Digital Repository (University of North Carolina at Chapel Hill) · doi:10.17615/3ttj-j094
TARGETING THE ERK MAPK PATHWAY IN RAS-DRIVEN CANCERS
Ryan, M. B. (2019) · Carolina Digital Repository (University of North Carolina at Chapel Hill) · doi:10.17615/jjj1-7f72
Cutaneous Malignant Melanoma and Targeted Therapy Based on the Biomarkers
Pandiaraja, J. (2019) · Indian Journal of Medical and Paediatric Oncology · doi:10.4103/ijmpo.ijmpo_204_18
Wong, T. C. (2018) · Digital Access to Scholarship at Harvard (DASH) (Harvard University)
Identification of Novel Targets for Therapy in Solid Tumors
Hutchinson, K. E. (2015)
Robust metabolic transcriptional components in 34,494 patient-derived samples and cell linesPreprint
Leeuwenburgh, V. C., Urzúa-Traslaviña, C. G., Bhattacharya, A., Walvoort, M. T. C., Jalving, M., de Jong, S., & Fehrmann, R. S. N. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.10.01.321950
Robust Metabolic Transcriptional Components in 34,494 Patient-Derived Samples and Cell LinesPreprint
Leeuwenburgh, V. C., Urzúa-Traslaviña, C. G., Bhattacharya, A., Walvoort, M. T. C., Jalving, M., de Jong, S., & Fehrmann, R. S. N. (2021) · Research Square · doi:10.21203/rs.3.rs-659596/v1
Wang, X., Kim, C., Zhang, Y., Rindhe, S., Cobb, M. H., & Yu, Y. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.05.20.444617
Rassaf, T., & Schadendorf, D. (2022) · Elsevier eBooks · doi:10.1016/b978-0-323-68135-3.00053-2
Targeted Therapies for BRAF-Mutant Metastatic Melanoma
Johnson, D. B., Dummer, R., Flaherty, K. T., & Smalley, K. S. M. (2020) · Springer eBooks · doi:10.1007/978-3-030-05070-2_40
Self-citationYang, J. H., Guo, L., Su, Y., & Zhang, Y. (2022) · Chinese Control Conference (CCC) · doi:10.23919/ccc55666.2022.9901550
Current Trends in Treatment and New Generation of Trials in Thyroid Cancer
Iyer, P. C., Srour, S. A., Hofmann, M.-C. C., & Cabanillas, M. E. (2023) · Springer eBooks · doi:10.1007/978-3-031-38605-3_21
Transcriptomic entropy reveals tissue-specific patterns in aging and predicts cancer progressionPreprint
dos Santos, G. A., Castro, J. P., & Galante, P. A. F. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.06.29.662218
Németh, A., Bányai, G. L., Dobos, N. K., Kós, T., Gaál, A., Varga, Z., Buzás, E. I., Khamari, D., Dank, M., Takács, I., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26724026
Leeuwenburgh, V. C., Urzúa-Traslaviña, C. G., Bhattacharya, A., Walvoort, M. T. C., Jalving, M., de Jong, S., & Fehrmann, R. S. N. (2021) · Figshare · doi:10.6084/m9.figshare.16683141
Melanoma Beyond the Microscope in the Era of AI and Integrated Diagnostics
Aksoy, S., Demircioğlu, P., & Böğrekçi, İ. (2026) · Dermato · doi:10.3390/dermato6010006
Marqueurs prédictifs de réponse aux inhibiteurs de BRAF dans le mélanome cutané métastatique
Funck-Brentano, E. (2016) · theses.fr (ABES) · doi:10.70675/73a2af67z6d03z483czb461zb0527aec1a30
Epigenetic regulation of gene expression during melanocyte and melanoma development
Laurette, P. (2016) · theses.fr (ABES) · doi:10.70675/b22b69c4z85a0z409czaccczc882ea46e923
Vercellino, L. (2017) · theses.fr (ABES) · doi:10.70675/bd83d31bz69ecz46a1z92b1z8e459d3f81ee
Mathematical Methods for Modelling Biological Heterogeneity
Hodgkinson, A. (2019) · theses.fr (ABES) · doi:10.70675/e9459bf2ze8f3z459cz9c28zf5629cbbd949
Identification et modulation des voies moléculaires impliquées dans l’agressivité du mélanome cutané
Gautron, A. (2019) · theses.fr (ABES) · doi:10.70675/b9c75939z7407z49abzafcbze6e92703d459
Molecular mechanisms of drug-tolerance to EGFR-targeted therapies in lung adenocarcinoma
Léonce, C. (2021) · theses.fr (ABES) · doi:10.70675/0611e924z7044z428cz90dcz9235e0a4b5a2
Serafini, M. (2024) · theses.fr (ABES) · doi:10.70675/ab8b1f5az3c15z4b5fzba28z247b40b8c7e0
Zhu, C., Wang, C., Zhu, Y., Yu, Z., Lin, Y., Zhang, Y., Jin, Y., Zhang, N., Liu, X., Ye, X., et al. (2026) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6c00836 · Cited by 1
Fu, H., Wang, M., Zhu, H., Li, W., Shen, X., Yan, H., & He, J. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27188031
Sologov, S. I., Sologova, D., Dubinin, D., Anikin, G., Bekhorashvili, N., Rayisyan, M., Krylova, E., Яркова, М. А., Grigorevskikh, E., Smolyarchuk, Е. А., et al. (2026) · Cancers · doi:10.3390/cancers18182950
Mutational landscape in cutaneous melanoma
Thielmann, C. M., Albrecht, L. J., Zaremba, A., Griewank, K., & Schadendorf, D. (2026) · EJC Skin Cancer · doi:10.1016/j.ejcskn.2026.101167
Xie, H., Wang, G., 原志庆, Li, Y., & Liu, Y. (2026) · Cancer Letters · doi:10.1016/j.canlet.2026.218931
Metadata
- Authors
- Wagle, N., Van Allen, E. M., Treacy, D. J., Frederick, D. T., Cooper, Z. A., Taylor-Weiner, A., Rosenberg, M., Goetz, E. M., Sullivan, R. J., Farlow, D. N., Friedrich, D. C., Anderka, K., Perrin, D., Johannessen, C. M., McKenna, A., Cibulskis, K., Kryukov, G., Hodis, E., Lawrence, D. P., Fisher, S., Getz, G., Gabriel, S. B., Carter, S. L., Flaherty, K. T., Wargo, J. A., & Garraway, L. A.
- Affiliations
- Broad Institute (US)
- Authors' Affiliations: 1Department of Medical Oncology, Dana-Farber Cancer Institute; 2Department of Medicine, Brigham and Women's Hospital; 3Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston; 4Broad Institute of Harvard and MIT; and 5Harvard–MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts
- Corresponding author
- Wargo, Jennifer A.
- Garraway, Levi A.
- ORCID
- Venue
- Cancer Discovery
- Published
- 2014-01-01
- Volume
- 4
- Issue
- 1
- Pages
- 61-68
- ISSN
- 2159-8274 (ISSN-L)
- 2159-8290
- PMC
- PMC3947296
- OpenAlex
- W2103557568
- Cited by
- 478
- References
- 27
- Citations by year
- 2026: 6 · 2025: 19 · 2024: 19 · 2023: 18 · 2022: 33 · 2021: 29 · 2020: 39 · 2019: 47 · 2018: 38 · 2017: 54 · 2016: 44 · 2015: 74 · 2014: 55
- FWCI
- 26.30
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Cancer Discovery (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (DP2OD002750)
- National Human Genome Research Institute (U54HG003067)
- National Cancer Institute (P50-CA-93683, R33CA155554, P01 CA163222 01A1, P50CA093683, T32CA009172, P30CA016672, P01CA163222)
- National Institute of General Medical Sciences (T32GM007753)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Keywords
- BRAF-mutant melanoma, acquired drug resistance, dabrafenib, trametinib, MEK2, MAPK pathway alterations, ERK inhibition, targeted therapy resistance, resistance mechanisms
- MeSH terms
- Aged, Antineoplastic Agents, Humans, Imidazoles, Male, Melanoma, Middle Aged, Mutation, Oximes, Pyridones, Pyrimidinones, Skin Neoplasms, Signal Transduction, Drug Resistance, Neoplasm, Mitogen-Activated Protein Kinases, Mitogen-Activated Protein Kinase Kinases, Protein Kinase Inhibitors, raf Kinases, Proto-Oncogene Proteins B-raf
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
