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Title: Resistance to antiangiogenic therapies by metabolic symbiosis in renal cell carcinoma PDX models and patients
Author: Jiménez-Valerio, Gabriela
Martínez-Lozano, Mar
Bassani, Nicklas
Vidal-Bel, August
Ochoa de Olza, Maria
Suárez, Cristina
García del Muro Solans, Xavier
Carles, Joan
Viñals Canals, Francesc
Graupera i Garcia-Milà, Mariona
Indraccolo, Stefano
Casanovas i Casanovas, Oriol
Keywords: Angiogènesi
Càncer de ronyó
Resistència als medicaments
Cèl·lules canceroses
Renal cancer
Drug resistance
Cancer cells
Issue Date: 10-May-2016
Publisher: Elsevier
Abstract: Antiangiogenic drugs are used clinically for treatment of renal cell carcinoma (RCC) as a standard first-line treatment. Nevertheless, these agents primarily serve to stabilize disease, and resistance eventually develops concomitant with progression. Here, we implicate metabolic symbiosis between tumor cells distal and proximal to remaining vessels as a mechanism of resistance to antiangiogenic therapies in patient-derived RCC orthoxenograft (PDX) models and in clinical samples. This metabolic patterning is regulated by the mTOR pathway, and its inhibition effectively blocks metabolic symbiosis in PDX models. Clinically, patients treated with antiangiogenics consistently present with histologic signatures of metabolic symbiosis that are exacerbated in resistant tumors. Furthermore, the mTOR pathway is also associated in clinical samples, and its inhibition eliminates symbiotic patterning in patient samples. Overall, these data support a mechanism of resistance to antiangiogenics involving metabolic compartmentalization of tumor cells that can be inhibited by mTOR-targeted drugs.
Note: Reproducció del document publicat a:
It is part of: Cell Reports, 2016, vol. 15, num. 6, p. 1134-1143
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ISSN: 2211-1247
Appears in Collections:Articles publicats en revistes (Ciències Fisiològiques)
Articles publicats en revistes (Patologia i Terapèutica Experimental)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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