Abstract One the most important challenges in the treatment of cancer is its evolving genomic intratumor heterogeneity. Tumors are composed of assortments of cells with subclonal genomic alterations that evolve following Darwinian selection. Glioblastoma (GBM) is a prototypical heterogeneous tumor and still little is known about how intratumor heterogeneity influences the progression of GBM and, most importantly, determines the response to treatments and tumor relapse. The study of the spatial and temporal genomic architecture of GBM is essential to understand the biology and improve the treatment of this dismal disease. Through the study of primary and relapsed tumors and patient-derived xenograft models (PDX) of GBM, we are studying the genomic subclones emerging after treatment since these subclones might be enriched in genomic alterations that confer a selective advantage and resistance to treatment. Putative genomic alterations involved in tumor resistance to treatment are further studied and validated through PDX models. Citation Format: Joan Seoane. Patient-derived xenograft models in glioblastoma. [abstract]. In: Proceedings of the AACR Special Conference: Patient-Derived Cancer Models: Present and Future Applications from Basic Science to the Clinic; Feb 11-14, 2016; New Orleans, LA. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(16_Suppl):Abstract nr IA16.