Development of Patient Derived Xenograft Models of Overt Spontaneous Breast Cancer Metastasis: A Cautionary Note

• DOI: 10.1371/journal.pone.0158034
• Publication Date: 2016-06-29T18:07:50Z
• Authors: Marta Paez-Ribes; Shan Man; Ping Xu; Robert S. Kerbel
• Keywords: Primary tumor

Several approaches are being evaluated to improve the historically limited value of studying transplanted primary tumors derived by injection cells from established cell lines for predicting subsequent cancer therapy outcomes in patients and clinical trials. These include use genetically engineered mouse models (GEMMs) spontaneous tumors, or patient tumor tissue xenografts (PDXs). Almost all such studies utilizing involve treatment tumors. An alternative approach we have developed involves human treat mice with overt visceral metastases after resection. The rationale is mimic more challenging circumstance treating late stage metastatic disease. entail prior vivo selection heritable, phenotypically stable variants increased aggressiveness metastasis; they were orthotopic followed resection serial distant metastases, which variant having a aggressive heritable phenotype established. We attempted adopt this strategy breast PDXs. studied five PDXs, emphasis on two, called HCI-001 HCI-002, both triple negative patients. However significant technical obstacles encountered. inherent slow growth rates rarity (detected only 3 144 mice), very high regrowths at site, failure few PDX isolated manifest upon re-transplantation into new hosts, formation de novo thymomas arising aged SCID that used experiments. discuss several possible strategies may be employed overcome these limitations. Uncovering basis detect rate reveal insights biology advanced