Artículo
Efficacy of bortezomib in sarcomas with high levels of MAP17 (PDZK1IP1
Autor/es | Pérez, Marco
Peinado Serrano, Javier García Heredia, José Manuel Felipe Abrio, Irene Tous Rivera, Cristina Ferrer, Irene Martín Broto, Javier |
Departamento | Universidad de Sevilla. Departamento de Bioquímica Vegetal y Biología Molecular |
Fecha de publicación | 2016 |
Fecha de depósito | 2017-04-24 |
Publicado en |
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Resumen | Sarcomas are malignant tumors accounting for a high percentage of cancer morbidity and mortality in children and young adults. Surgery and radiation therapy are the accepted treatments for most sarcomas; however, patients ... Sarcomas are malignant tumors accounting for a high percentage of cancer morbidity and mortality in children and young adults. Surgery and radiation therapy are the accepted treatments for most sarcomas; however, patients with metastatic disease are treated with systemic chemotherapy. Many tumors display marginal levels of chemoresponsiveness, and new treatment approaches are needed. MAP17 is a small non-glycosylated membrane protein overexpressed in carcinomas. The levels of MAP17 could be used as a prognostic marker to predict the response to bortezomib in hematological malignancies and in breast tumors. Therefore, we analyzed the expression of this oncogene in sarcomas and its relationship with clinico-pathological features, as well as tested whether it can be used as a new biomarker to predict the therapeutic response to bortezomib and new therapies for sarcomas. We found that the levels of MAP17 were related to clinical features and poor survival in a cohort of 69 patients with different sarcoma types, not being restricted to any special subtype of tumor. MAP17 expression is associated with poor overall survival (p<0.001) and worse disease-free survival (p=0.002). Cell lines with high levels of MAP17 show a better response to bortezomib in vitro. Furthermore, patient-derived xenografts (PDX) with high levels of MAP17 respond to bortezomib in vivo. Our results showed that this response is due to the lower levels of NFκB and autophagy activation. Therefore, we suggest that MAP17 is a new biomarker to predict the efficacy of bortezomib as a new therapy for sarcomas. |
Identificador del proyecto | CTS-6844
CTS-1848 PI-0029-2013 PI-0096-2014 PI-0306-2012 |
Cita | Pérez, M., Peinado Serrano, J., García Heredia, J.M., Felipe Abrio, I., Tous Rivera, C., Ferrer, I. y Martín Broto, J. (2016). Efficacy of bortezomib in sarcomas with high levels of MAP17 (PDZK1IP1. Oncotarget, 7 (41), 67033-67046. |
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