Resistance to antiangiogenic therapies by metabolic symbiosis in renal cell carcinoma PDX models and patients

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 tu...

Descripción completa

Detalles Bibliográficos
Autores: Jiménez Valerio, Gabriela, Martínez Lozano, Mar, Bassani, Nicklas, Vidal-Bel, August, Ochoa de Olza, Maria, Suarez, Cristina, García del Muro Solans, Xavier, Carles, Joan, Viñals Canals, Francesc, Graupera i Garcia-Milà, Mariona, Indraccolo, Stefano, Casanovas i Casanovas, Oriol
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2016
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/116803
Acceso en línea:https://hdl.handle.net/2445/116803
Access Level:acceso abierto
Palabra clave:Angiogènesi
Càncer de ronyó
Resistència als medicaments
Cèl·lules canceroses
Neovascularization
Renal cancer
Drug resistance
Cancer cells
Descripción
Sumario: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.

Similares en LA Referencia