The use of preclinical models is essential in every aspect of translational cancer research, from the biologic understanding of the disease to the development of new treatments. Patient Derived Xenograft (PDX) models are increasingly used in translational cancer research due to their advantages over other preclinical models. However, although it has been widely demonstrate that these kind of models are predictive of clinical outcome, there are also some drawbacks when working with them.
Analyzing our PDX model collection, we have observed that there is a small percentage of cases in which a murine tumor is developed instead of the original human one by a process that has been called horizontal oncogenesis. This process was already observed and described in the early 80´s, however, it is still not well understood and the molecular mechanisms by which it happens remain unknown.
In order to determine the origin of the different murine tumors observed in our mice, we performed immunohistochemistry characterization of our altered models and found two different types of murine tumors: murine fibrosarcomas, which were observed in Colorectal and Pancreatic Ductal Adenocarcinoma PDX models; and murine lymphomas, that were observed mainly in Lung PDX models when they were implanted in Nod-scid mice. We also found a case in which a human lymphoproliferation grew in the animals instead of the sample from the small cell lung cancer obtained from the patient.
As these murine tumors grow in the same place where the human donor tumor was implanted, it is important to have a quick and effective method to identify them before performing any study with these altered models. In this regard, we have implemented a simple technique based on PCR analysis with primers that recognize K-Ras. We have designed an estrategy in which we can obtain amplicons of different sizes depending on their human or murine origin.
Although we still have to analize some of our PDX models, using this methodology we have confirmed that murine tumors appear in a very low percentage of cases (less than 5% to date). However, even with this low incidence we consider that is essential to identify those murine tumors as soon as possible in order to avoid wasting time, money and resources.
Citation Format: Camino Menéndez, Beatriz Salvador, Manuel Muñoz, Natalia Baños, Francesca Sarno, Pedro P López-Casas, Manuel Hidalgo. When murine tumors are thought to be human: A drawback of patient derived xenografts.. [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 B44.
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