Individualized strategies to target specific mechanisms of disease in malignant melanoma patients displaying unique mutational signatures. [artículo]
Por: Ortiz Romero, Pablo Luis [Dermatología Médico-Quirúrgica y Venereología]
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Colaborador(es): Servicio de Dermatología Médico-Quirúrgica y Venereología
| Instituto de Investigación imas12
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Tipo de material: ![materialTypeLabel](/opac-tmpl/lib/famfamfam/AR.png)
Tipo de ítem | Ubicación actual | Signatura | Estado | Fecha de vencimiento |
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PC17096 (Navegar estantería) | Disponible |
Formato 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.
PMID: 26327537
PMC4694844.
Contiene 42 referencias
Erratum in: Oncotarget. 2016 Feb 2;7(5):6352.
Targeted 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.
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