Intratumoral Molecular Heterogeneity in a BRAF-Mutant, BRAF Inhibitor-Resistant Melanoma: A Case Illustrating the Challenges for Personalized Medicine
| Autor: | Roger S. Lo, Varsha Tembe, Helen Rizos, Richard F. Kefford, John F. Thompson, James S. Wilmott, Richard A. Scolyer, Julie Howle, Raghwa Sharma, Georgina V. Long |
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| Rok vydání: | 2012 |
| Předmět: |
Male
Proto-Oncogene Proteins B-raf Neuroblastoma RAS viral oncogene homolog Cancer Research medicine.disease_cause Metastasis medicine Humans Neoplasm Metastasis Precision Medicine Vemurafenib Melanoma Aged business.industry Cancer medicine.disease Oncology Drug Resistance Neoplasm Mutation Immunology Cancer research Personalized medicine Carcinogenesis business V600E medicine.drug |
| Zdroj: | Molecular Cancer Therapeutics. 11:2704-2708 |
| ISSN: | 1538-8514 1535-7163 |
| Popis: | 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. Mol Cancer Ther; 11(12); 2704–8. ©2012 AACR. |
| Databáze: | OpenAIRE |
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