Figure 3.

Clinical-Translational Model Incorporating Patient-Derived Xenografts. Two patient-derived xenograft (PDX) clinical-translational models are shown. The tumor avatar approach (Top panel) is one in which the patient's tumor is used to generate a PDX that will directly inform his or her own therapy. A schematic is shown for one potential tumor avatar design in which an individual patient and a PDX derived from this patient's own cancer are given standard of care (SOC) therapy, such as chemotherapy (chemo) and radiation (XRT). When the PDX develops resistance to the SOC, the resistant PDX is then expanded and tested against potential second line therapies (Tx1-4). The winning therapy (indicated by trophy) is then selected for second line therapy for the patient when they develop tumor recurrence following SOC. A tumor proband approach is shown schematically (bottom panel). In a proband model system, a cohort of PDX are utilized that represent the spectrum of human disease for that tumor type. These PDX are molecularly profiled and tested against various therapeutic regimens, such as irradiation (XRT), chemotherapeutics, and small molecule inhibitors. Ideally, molecular profiling is performed longitudinally (i.e., pre- and post- therapy) as molecular profiles likely change due to tumor adaptation/response. Well-characterized PDX will generate a library of profiling and phenotype information that can be used to inform clinical decisions as follows: a patient's tumor is molecularly profiled and matched to a particular or multiple PDX and known therapeutic sensitivity information is then passed back to the clinician for selection of proband-directed therapy.