Intratumoral molecular heterogeneity in a BRAF-mutant, BRAF inhibitor-resistant melanoma: a case illustrating the challenges for personalized medicine - PubMed (original) (raw)
Case Reports
. 2012 Dec;11(12):2704-8.
doi: 10.1158/1535-7163.MCT-12-0530. Epub 2012 Sep 7.
Affiliations
- PMID: 22962325
- DOI: 10.1158/1535-7163.MCT-12-0530
Case Reports
Intratumoral molecular heterogeneity in a BRAF-mutant, BRAF inhibitor-resistant melanoma: a case illustrating the challenges for personalized medicine
James S Wilmott et al. Mol Cancer Ther. 2012 Dec.
Abstract
Targeted therapies are increasingly being used to treat a variety of cancers. Their efficacy depends upon the accurate detection and targeting of a specific mutation or aberration in the tumor. All cancers, such as melanoma, are molecularly heterogeneous, with drug-resistant subclones present before the treatment or emerging as a result of targeted therapies. Here, we show intralesional molecular heterogeneity in a progressing V600E BRAF-mutant melanoma metastasis from a patient treated for 7 months with the BRAF inhibitor vemurafenib. In the single metastasis, two distinct subclones were observed, both V600E BRAF-mutant and only one with an additional G13R NRAS mutation. Molecular heterogeneity even at the intralesional level shows that personalizing or adjusting therapies based on genotyping of a portion of a single lesion may not accurately depict the molecular profile or drivers of oncogenesis across the entire patient's melanoma.
Similar articles
- BRAF Fusion as a Novel Mechanism of Acquired Resistance to Vemurafenib in _BRAF_V600E Mutant Melanoma.
Kulkarni A, Al-Hraishawi H, Simhadri S, Hirshfield KM, Chen S, Pine S, Jeyamohan C, Sokol L, Ali S, Teo ML, White E, Rodriguez-Rodriguez L, Mehnert JM, Ganesan S. Kulkarni A, et al. Clin Cancer Res. 2017 Sep 15;23(18):5631-5638. doi: 10.1158/1078-0432.CCR-16-0758. Epub 2017 May 24. Clin Cancer Res. 2017. PMID: 28539463 - Overcoming acquired BRAF inhibitor resistance in melanoma via targeted inhibition of Hsp90 with ganetespib.
Acquaviva J, Smith DL, Jimenez JP, Zhang C, Sequeira M, He S, Sang J, Bates RC, Proia DA. Acquaviva J, et al. Mol Cancer Ther. 2014 Feb;13(2):353-63. doi: 10.1158/1535-7163.MCT-13-0481. Epub 2014 Jan 7. Mol Cancer Ther. 2014. PMID: 24398428 - Detailed imaging and genetic analysis reveal a secondary BRAF(L505H) resistance mutation and extensive intrapatient heterogeneity in metastatic BRAF mutant melanoma patients treated with vemurafenib.
Hoogstraat M, Gadellaa-van Hooijdonk CG, Ubink I, Besselink NJ, Pieterse M, Veldhuis W, van Stralen M, Meijer EF, Willems SM, Hadders MA, Kuilman T, Krijgsman O, Peeper DS, Koudijs MJ, Cuppen E, Voest EE, Lolkema MP. Hoogstraat M, et al. Pigment Cell Melanoma Res. 2015 May;28(3):318-23. doi: 10.1111/pcmr.12347. Epub 2015 Jan 7. Pigment Cell Melanoma Res. 2015. PMID: 25515853 - The discovery of vemurafenib for the treatment of BRAF-mutated metastatic melanoma.
Kim A, Cohen MS. Kim A, et al. Expert Opin Drug Discov. 2016 Sep;11(9):907-16. doi: 10.1080/17460441.2016.1201057. Epub 2016 Jun 23. Expert Opin Drug Discov. 2016. PMID: 27327499 Free PMC article. Review. - Vemurafenib in patients with BRAF V600E mutation-positive advanced melanoma.
Ravnan MC, Matalka MS. Ravnan MC, et al. Clin Ther. 2012 Jul;34(7):1474-86. doi: 10.1016/j.clinthera.2012.06.009. Epub 2012 Jun 27. Clin Ther. 2012. PMID: 22742884 Review.
Cited by
- BRAFV600E immunopositive melanomas show low frequency of heterogeneity and association with epithelioid tumor cells: a STROBE-compliant article.
Verlinden I, van den Hurk K, Clarijs R, Willig AP, Stallinga CMHA, Roemen GMJM, van den Oord JJ, Zur Hausen A, Speel EM, Winnepenninckx VJL. Verlinden I, et al. Medicine (Baltimore). 2014 Dec;93(28):e285. doi: 10.1097/MD.0000000000000285. Medicine (Baltimore). 2014. PMID: 25526463 Free PMC article. - Melanoma patient derived xenografts acquire distinct Vemurafenib resistance mechanisms.
Monsma DJ, Cherba DM, Eugster EE, Dylewski DL, Davidson PT, Peterson CA, Borgman AS, Winn ME, Dykema KJ, Webb CP, MacKeigan JP, Duesbery NS, Nickoloff BJ, Monks NR. Monsma DJ, et al. Am J Cancer Res. 2015 Mar 15;5(4):1507-18. eCollection 2015. Am J Cancer Res. 2015. PMID: 26101714 Free PMC article. - Dabrafenib and its potential for the treatment of metastatic melanoma.
Menzies AM, Long GV, Murali R. Menzies AM, et al. Drug Des Devel Ther. 2012;6:391-405. doi: 10.2147/DDDT.S38998. Epub 2012 Dec 11. Drug Des Devel Ther. 2012. PMID: 23251089 Free PMC article. Review. - Converting biology into clinical benefit: lessons learned from BRAF inhibitors.
McQuade J, Davies MA. McQuade J, et al. Melanoma Manag. 2015;2(3):241-254. doi: 10.2217/mmt.15.18. Melanoma Manag. 2015. PMID: 26594316 Free PMC article. - Primary and Metastatic Melanoma With NTRK Fusions.
Lezcano C, Shoushtari AN, Ariyan C, Hollmann TJ, Busam KJ. Lezcano C, et al. Am J Surg Pathol. 2018 Aug;42(8):1052-1058. doi: 10.1097/PAS.0000000000001070. Am J Surg Pathol. 2018. PMID: 29683819 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
Research Materials
Miscellaneous