Project Summary The goal of our proposed Coordinating and Data Management Center (CDMC) application is to coordinate the activities across the Acquired Resistance to Therapy Network (ARTNet), and to manage, integrate and disseminate the data and resources generated through the network. Leveraging cutting-edge multi-disciplinary team approaches, we will support the ARTNet to inform new strategies that can be better translated to overcome significant challenges in acquired resistance to cancer therapies. Our strategy is to enhance the productivity of ARTNet investigators by fostering a collaborative and supportive research community, accelerate the progress of ARTNet research by reducing barriers to accessing analytical expertise, ensure the reproducibility of ARTNet data by deploying best practices for data acquisition and harmonization, and unleash the full potential of ARTNet activities by developing enhanced tools to enable resource sharing to the broader scientific community. First, we will provide a centralized administrative infrastructure to coordinate ARTNet activities, building upon our well-functioning infrastructure that currently coordinates network studies under the umbrella of the NCI Cancer Moonshot initiatives. Second, we will actively promote the ARTNet and engage in trans-consortium interactions, where we will leverage our demonstrable experience in Cross-Moonshot outreach and Bioconductor’s decades-long record in community engagement. Third, we will provide multidisciplinary analytical expertise to support ARTNet collaborative research, leveraging five of Roswell Park CCSG’s shared resources: Biostatistics, Bioinformatics, Biomedical Informatics, Pharmacokinetics/Pharmacodynamics, and Data Bank and BioRepository. Our analytical support will be provided at no cost to ARTNet investigators in need of analytical expertise, based on collaboration, transparency, and sharing. Fourth, we will develop improved data integration software and workflows to enhance ARTNet’s research capacity, capitalizing on our extensive track-record in developing NIH-supported Moonshot, Bioconductor and AnVIL ecosystems. The main deliverables from the proposed aims will be administrative and outreach support to coordinate network activities, facilitate network collaboration, and engage in interaction with the broader community (Aim 1); polices and infrastructures to ensure that all resources generated by the ARTNet will be findable in a centralized virtual resource sharing repository, and that all resources will be shared with the broader scientific community (Aim 2); workflows to ensure that all data generated by the ARTNet will be harmonized using standards interoperable with the broader cancer data ecosystem, analysis tools to integrate ARTNet data and facilitate cross-study analysis within and beyond the ARTNet, and multidisciplinary analytical supports to accelerate ARTNet research progress.(Aim 3).

Project Narrative While advances in cancer therapeutics have resulted in remarkable clinical responses in some patients, acquired resistance remains one of the biggest challenges towards expanding the clinical benefits to more patients. Tackling acquired therapy resistance will require collaborative efforts to elucidate resistance mechanisms, characterize the tumor microenvironment, discover new targets, identify predictive biomarkers, evaluate combination therapies, and develop real-time monitoring approaches. The goal of our proposed Coordinating and Data Management Center (CDMC) application is to coordinate the activities across the Acquired Resistance to Therapy Network (ARTNet), and to manage, integrate and disseminate the data and resources generated through the network. Leveraging cutting-edge multi-disciplinary team approaches, we will support the ARTNet to inform new strategies that can be better translated to overcome significant challenges in acquired resistance to cancer therapies.