2026-04-14T04:22:59Zhttps://recercat.cat/oai/request

oai:recercat.cat:2445/1168032025-12-05T09:21:10Zcom_2072_1057col_2072_478799col_2072_478916col_2072_478917col_2072_478929

00925njm 22002777a 4500 dc Jiménez Valerio, Gabriela author Martínez Lozano, Mar author Bassani, Nicklas author Vidal-Bel, August author Ochoa de Olza, Maria author Suarez, Cristina author García del Muro Solans, Xavier author Carles, Joan author Viñals Canals, Francesc author Graupera i Garcia-Milà, Mariona author Indraccolo, Stefano author Casanovas i Casanovas, Oriol author 2017-10-19T12:11:46Z 2017-10-19T12:11:46Z 2016-05-10 2017-10-19T12:11:46Z 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. Angiogènesi Càncer de ronyó Resistència als medicaments Cèl·lules canceroses Neovascularization Renal cancer Drug resistance Cancer cells Resistance to antiangiogenic therapies by metabolic symbiosis in renal cell carcinoma PDX models and patients