Patient-Derived Xenograft Models for Endometrial Cancer Research

Abstract

Endometrial cancer (EC) is the most common malignancy of the genital tract among women in developed countries. Recently, a molecular classification of EC has been performed providing a system that, in conjunction with histological observations, reliably improves EC classification and enhances patient management. Patient-derived xenograft models (PDX) represent nowadays a promising tool for translational research, since they closely resemble patient tumour features and retain molecular and histological features. In EC, PDX models have already been used, mainly as an individualized approach to evaluate the efficacy of novel therapies and to identify treatment-response biomarkers; however, their uses in more global or holistic approaches are still missing. As a collaborative effort within the ENITEC network, here we describe one of the most extensive EC PDX cohorts developed from primary tumour and metastasis covering all EC subtypes. Our models are histologically and molecularly characterized and represent an excellent reservoir of EC tumour samples for translational research. This review compiles the information on current methods of EC PDX generation and their utility and provides new perspectives for the exploitation of these valuable tools in order to increase the success ratio for translating results to clinical practice.

Patient-derived non-small cell lung cancer xenograft mirrors complex tumor heterogeneity

“…With the rapid development of genotype-based individualized targeted therapies, preclinical trials using in vitro and in vivo models are essential in elucidating gene function and validating potential therapeutic targets 8 . In the last decade, a series of patient-derived xenograft (PDX) models have been developed and have rapidly gained favor over use of conventional cell lines as a preclinical drug screening platform, including for pancreatic cancer 9 , 10 , colorectal cancer 11 – 13 , hepatocellular carcinoma 14 , 15 , breast cancer 16 , 17 , epithelial ovarian cancer 18 , esophageal cancer 19 , 20 , and other cancers 21 – 23 . These PDX-based preclinical models accurately recapitulate the pathological and molecular characteristics of corresponding individual tumors, better reflecting patient heterogeneity and clinical diversity.…”

Changes in Stem Cell Regulation and Epithelial Organisation during Carcinogenesis and Disease Progression in Gynaecological Malignancies

“…This approach would help to build upon unique advantages of PDOs in comparison to other valuable disease models such as patient derived xenografts (PDXs). The latter are still considered as "gold standard" to assess tumourigenic potential of any cancer type, and have been successfully created for gynaecological malignancies [110,111]. However, despite providing clear benefits as in vivo experimental models [112], PDXs do have limitation of xeno-tissue environment.…”

Near-Infrared Fluorescent Imaging for Monitoring of Treatment Response in Endometrial Carcinoma Patient-Derived Xenograft Models

“…Thus, PDX models are not only anticipated to capture both the intra-and inter-tumor heterogeneity of endometrial carcinoma, as has been previously demonstrated for breast, lung and pancreatic cancer, but also to faithfully reproduce clinical responses to chemotherapy [16,17]. Critically, orthotopic PDX models, i.e., where primary biopsies are implanted into the organ/microenvironment of origin, are proposed as a superior paradigm of clinical disease compared with subcutaneous PDX [18][19][20]. However, a major caveat of the orthotopic approach, particularly with patient-derived material, is longitudinal and spatio-temporal monitoring of not only disease development and characterization but also for further intervention studies.…”