2026-04-14T03:41:54Zhttps://recercat.cat/oai/request

oai:recercat.cat:2445/2133832025-12-05T10:09:24Zcom_2072_1057col_2072_478916col_2072_478917col_2072_478929

00925njm 22002777a 4500 dc Moserle, Lidia author Pons, Roser author Martínez-Lozano, Mar author Jiménez Valerio, Gabriela author Vidal, August author Suárez, Cristina author Trilla Herrera, Enrique author Jiménez, José author de Torres, Inés author Carles, Joan author Senserrich, Jordi author Aguilar, Susana author Palomero, Luis author Amadori, Alberto author Casanovas, Oriol author 2024-06-18T15:30:54Z 2024-06-18T15:30:54Z 2020-12-07 2024-06-18T15:30:59Z An open debate in antiangiogenic therapies is about their consequence on tumor invasiveness and metastasis, which is undoubtedly relevant for patients currently treated with antiangiogenics, such as renal cell carcinoma patients. To address, this we developed an extensive series of 27 patient biopsy-derived orthotopic xenograft models (Ren-PDOX) that represent inter-patient heterogeneity. In specific tumors, antiangiogenics produced increased invasiveness and metastatic dissemination, while in others aggressiveness remained unchanged. Mechanistically, species-discriminative RNA sequencing identified a tumor cell-specific differential expression profile associated with tumor progression and aggressivity in TCGA RCC patients. Gene filtering using an invasion-annotated patient series pinpointed two candidate genes, of which ALDH1A3 differentiated the pro-invasive subtype of Ren-PDOXs. Validation in an independent series of 15 antiangiogenic-treated patients confirmed that pre-treatment ALDH1A3 can significantly discriminate patients with pro-aggressive response upon treatment. Overall, results confirm that effects of antiangiogenic drugs on tumor invasion and metastasis are heterogeneous and may profoundly affect the natural progression of tumors and promote malignancy. Furthermore, we identify a specific molecular biomarker that could be used to select patients that better benefit from treatment. Tumors Càncer de ronyó Angiogènesi Animals Tumors Renal cancer Neovascularization Animals Kidney cancer PDOXs reveal patient-specific pro-malignant effects of antiangiogenics and its molecular traits