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040 _cH12O
041 _aeng
100 _91223
_aOrtiz Romero, Pablo Luis
_eDermatología Médico-Quirúrgica y Venereología
245 0 0 _aIndividualized strategies to target specific mechanisms of disease in malignant melanoma patients displaying unique mutational signatures.
_h[artículo]
260 _bOncotarget,
_c2015
300 _a6(28):25452-65.
500 _aFormato Vancouver: Curiel Olmo S, García Castaño A, Vidal R, Pisonero H, Varela I, León Castillo A et al. Individualized strategies to target specific mechanisms of disease in malignant melanoma patients displaying unique mutational signatures. Oncotarget. 2015 Sep 22;6(28):25452-65.
501 _aPMID: 26327537 PMC4694844.
504 _aContiene 42 referencias
505 _aErratum in: Oncotarget. 2016 Feb 2;7(5):6352.
520 _aTargeted treatment of advanced melanoma could benefit from the precise molecular characterization of melanoma samples. Using a melanoma-specific selection of 217 genes, we performed targeted deep sequencing of a series of biopsies, from advanced melanoma cases, with a Breslow index of ≥ 4 mm, and/or with a loco-regional infiltration in lymph nodes or presenting distant metastasis, as well of a collection of human cell lines. This approach detected 3-4 mutations per case, constituting unique mutational signatures associated with specific inhibitor sensitivity. Functionally, case-specific combinations of inhibitors that simultaneously targeted MAPK-dependent and MAPK-independent mechanisms were most effective at inhibiting melanoma growth, against each specific mutational background. These observations were challenged by characterizing a freshly resected biopsy from a metastatic lesion located in the skin and soft tissue and by testing its associated therapy ex vivo and in vivo using melanocytes and patient-derived xenografted mice, respectively. The results show that upon mutational characterization of advanced melanoma patients, specific mutational profiles can be used for selecting drugs that simultaneously target several deregulated genes/pathways involved in tumor generation or progression.
710 _9145
_aServicio de Dermatología Médico-Quirúrgica y Venereología
710 _9625
_aInstituto de Investigación imas12
856 _uhttps://pubmed.ncbi.nlm.nih.gov/26327537/
_yAcceso libre
942 _2ddc
_cART
_n0