Xenograft Animal Models Recapitulate Genetic Behavior of Original Human Tumors

  • Researchers from IDIBELL and ICO have participated in a multicenter study, published in Nature Genetics, which shows that the implantation of human tumors in nude mice does not lead to additional DNA changes.
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Animal models of xenograft are generated through the implantation of human tumors in mice. In these models, the human tumor is implanted either in the subcutaneous tissue of the mouse (called PDX, Patient-Derived Xenografts) or in the same organ of origin (called PDOX or Orthoxenografts). These preclinical models are widely used in drug efficacy studies since they allow researchers to study human tumor cells in tissue in vivo, also, to carry out molecular studies, and identify new therapeutic targets.

Genomic and histological studies have shown that tumors implanted in mice retain their original biological characteristics. However, it has been questioned whether tumor growth in mouse tissue could be altering its progression and affecting cancer-related genes, which in the second instance could afect the results of pharmacological efficacy.

A study published in the journal Nature Genetics has compared genetic changes of 509 models, most of them subcutaneous, with their corresponding original human tumors and found no significant differences. Specifically, they have measured alterations in the number of copies, that is, losses or gains of DNA fragments.

The study included the participation of IDIBELL and ICO researchers: Purificación Muñoz, Eva Gonzalez Suarez (also a CNIO researcher), as well as, Oriol Casanovas and Alberto Villanueva, both from ProCure. All of them within the European EurOPDX consortium, in close relationship with the PDXnet consortium of the National Cancer Institut (NCI) (USA).

The study concludes that the progression of tumors in mouse tissue does not entail genetic changes that could affect the behavior of the model and move it away from the behavior of the original tumor of the patient. In fact, the small variations detected between the two groups were of the same order as the variations that can be found in different regions of the same tumor.

 

The Bellvitge Biomedical Research Institute (IDIBELL) is a biomedical research center created in 2004. It is participated by the Bellvitge University Hospital and the Viladecans Hospital of the Catalan Institute of Health, the Catalan Institute of Oncology, the University of Barcelona and the City Council of L’Hospitalet de Llobregat.

IDIBELL is a member of the Campus of International Excellence of the University of Barcelona HUBc and is part of the CERCA institution of the Generalitat de Catalunya. In 2009 it became one of the first five Spanish research centers accredited as a health research institute by the Carlos III Health Institute. In addition, it is part of the “HR Excellence in Research” program of the European Union and is a member of EATRIS and REGIC. Since 2018, IDIBELL has been an Accredited Center of the AECC Scientific Foundation (FCAECC).

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