Generation and Integrated Analysis of Advanced Patient- derived Orthoxenograft Models (PDOX) for the Rational Assessment of Targeted Therapies in Endometrial Cancer

ABSTRACT: Clinical management of endometrial cancer (EC) is handicapped by the limited availability of second line treatments and bona fide molecular biomarkers to predict recurrence. These limitations have hampered the treatment of these patients, whose survival rates have not improved over the last four decades. The advent of coordinated studies such as the TCGA_UCEC have partially solved this issue, but the lack of proper experimental systems still represents a bottleneck that precludes translational studies from successful clinical testing in EC patients. Within this context, we present the first study reporting the generation of a collection of endometrioid EC patient-derived orthoxenograft (PDOX) mouse models that we believe can overcome these experimental constraints and pave the way towards state-of-the-art precision medicine in EC. We have characterized our collection of primary tumors and derived PDOXs through an integrative approach based on transcriptomics, mutational profiles and morphological analysis; and demonstrate that EC tumors engrafted in the mouse uterus retain the main molecular and morphological features from analogous tumor donors. Finally, we have harnessed the molecular properties of these tumors to assess the therapeutic potential of trastuzumab, a HER2 inhibitor with growing interest in EC, using patient-derived organotypic multicellular tumor spheroids and in vivo experiments.

ORGANISM(S): Homo sapiens

PROVIDER: GSE214657 | GEO | 2022/10/25

REPOSITORIES: GEO