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Nat Commun ; 12(1): 5049, 2021 08 19.
Artículo en Inglés | MEDLINE | ID: mdl-34413304

RESUMEN

Preclinical testing is a crucial step in evaluating cancer therapeutics. We aimed to establish a significant resource of patient-derived xenografts (PDXs) of prostate cancer for rapid and systematic evaluation of candidate therapies. The PDX collection comprises 59 tumors collected from 30 patients between 2012-2020, coinciding with availability of abiraterone and enzalutamide. The PDXs represent the clinico-pathological and genomic spectrum of prostate cancer, from treatment-naïve primary tumors to castration-resistant metastases. Inter- and intra-tumor heterogeneity in adenocarcinoma and neuroendocrine phenotypes is evident from bulk and single-cell RNA sequencing data. Organoids can be cultured from PDXs, providing further capabilities for preclinical studies. Using a 1 x 1 x 1 design, we rapidly identify tumors with exceptional responses to combination treatments. To govern the distribution of PDXs, we formed the Melbourne Urological Research Alliance (MURAL). This PDX collection is a substantial resource, expanding the capacity to test and prioritize effective treatments for prospective clinical trials in prostate cancer.


Asunto(s)
Evaluación Preclínica de Medicamentos/métodos , Organoides/patología , Neoplasias de la Próstata/patología , Animales , Modelos Animales de Enfermedad , Genoma , Humanos , Masculino , Ratones , Ratones Endogámicos NOD , Ratones SCID , Mutación , Metástasis de la Neoplasia , Organoides/metabolismo , Estudios Prospectivos , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/metabolismo , Bancos de Tejidos , Transcriptoma , Ensayos Antitumor por Modelo de Xenoinjerto
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