Summary: The goals of the Pilot Projects and Trans-Network Activities Core of the UP-PDTC focus on two priorities. First, the Core will promote and support new Pilot Projects with high scientific merit and innovation that will strongly impact PDX model development research and/or have the potential for translation to the clinic. The Core will specifically act as a focal point and resource to bring new ideas, technologies, interventions, and researchers into the UP-PDTC and the PDXNet. Second, the Pilot Projects and Trans-Network Core will prioritize and facilitate novel projects that can add to the translational capabilities of the PDXNet. Key criteria for project selection will include 1) high expected impact; 2) translational potential that may eventually be integrated into full projects within the UP-PDTC or PDXNet; 3) innovative ideas and approaches that generate new hypotheses and preliminary data; 4) collaborations to develop novel research and research tools, 5) high risk/high return projects that move basic science and/or clinical interventions and 6) development of tissue collections that address cancer disparities. Although the UP-PDTC will be a T-PDTC, we acknowledge and highly support the latter goal. Pilot project grants will be competitively financially supported by the Core budget and the PDX Core personnel will work with Pilot Project PI’s to develop application to the TransNetwork program and/or for specific R01 applications. Solicitations for Core projects are made within the University of Pennsylvania Abramson Cancer Center. Specific efforts will be made to recruit Pilot Project applicants from underrepresented minorities (URM), women, and individuals with disabilities. The UP-PDTC Administrative Core will assist in implementing a coordinated process for review, selection, and monitoring Pilot Projects, ensuring that UP-PDTC resources are used effectively to expand PDX modeling, interactions with the PDXNet and PDXNet research. The influx of research from new PDX modelers and investigators, or from those with expertise outside of the most common tumors, will foster innovative new directions and complement ongoing efforts in the UP-PDTC and PDXNet.