Efficacy of bortezomib in sarcomas with high levels of MAP17 (PDZK1IP1)

// Marco Perez 1 , Javier Peinado-Serrano 1 , Jose Manuel Garcia-Heredia 1, 2 , Irene Felipe-Abrio 1 , Cristina Tous 1 , Irene Ferrer 1 , Javier Martin-Broto 1, 3 , Carmen Saez 1, 4 , Amancio Carnero 1 1 Instituto de Biomedicina de Sevilla, IBIS, Hospital Universitario Virgen del Rocio, Universidad de Sevilla, Consejo Superior de Investigaciones Cientificas, Seville, Spain 2 Department of Vegetal Biochemistry and Molecular Biology, University of Seville, Seville, Spain 3 Department of Medical Oncology, Virgen del Rocio University Hospital, Seville, Spain 4 Department of Pathology, Virgen del Rocio University Hospital, Seville, Spain Correspondence to: Amancio Carnero, email: acarnero-ibis@us.es Keywords: MAP17, bortezomib, PDX, sarcomas, biomarker Received: March 08, 2016      Accepted: August 09, 2016      Published: August 22, 2016 ABSTRACT 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.