This application is being submitted in response to the Notice of Special Interest (NOSI) identified as NOT-CA- 20-052. Project Summary While several innovative and creative anti-cancer therapies have shown promising results, a significant expansion of their clinical use will require collaborative efforts to elucidate resistance mechanisms, exploit tumor sensitivity, map cancer dependence, discover new targets, identify predictive biomarkers, evaluate combination therapies, and develop real-time monitoring approaches. Leveraging cutting-edge multi-disciplinary team approaches, we will support the NCI Drug Resistance and Sensitivity Network (DRSN) to understand and combat mechanisms of tumor resistance and to exploit tumor sensitivity to anti-cancer therapies. Our strategy is to serve as an administration, communication, collaboration and analysis hub to coordinate the DRSN?s network-wide studies, focusing on reducing barriers to domain expertise, improving the productivity of DRSN investigators, maintaining a high standard for data harmonization and integration, designing and implementing rigorous analytical strategies, and fostering a collaborative and supportive research community. An experienced, multidisciplinary team has been assembled to pursue five Specific Aims: First, we will provide a centralized administration infrastructure to coordinate DRSN activities, building upon the Immuno-Oncology Translational Network (IOTN) Data Management and Resource-sharing Center (DMRC)?s well-functioning infrastructure that currently coordinates network studies under the umbrella of the NCI Cancer Moonshot initiative. Second, we will actively promote the DRSN and foster trans-consortium interactions, where we will leverage the IOTN DMRC?s demonstrable experience in Cross-Moonshot outreach and Bioconductor?s decades-long record in community-wide engagement. Third, we will provide multidisciplinary expertise to support DRSN collaborative research, leveraging four of the Roswell Park CCSG?s shared resources: Biostatistics, Bioinformatics, Data Bank and BioRepository, Bioanalytics, Metabolomics & Pharmacokinetics. Our analytic support will be armed with professional IT staff and informed by an experienced anti-cancer therapeutic researcher team. Fourth, we will develop innovative multi-omics data integration methods to enhance DRSN?s research capacity, capitalizing on the well-respected and highly-successful Bioconductor project. Fifth, we will disseminate resources developed in the DRSN to the broader community, unleashing the full potential of DRSN activities. Taken together, we envision our CC, in close collaboration with the DRSN components, will allow us to conduct highly effective and innovative translational studies to address the significantly unmet needs related to anti-cancer therapeutics, and fulfill the expectations and guiding principles of NCI Cancer Moonshot initiative.
While several innovative and creative anti-cancer therapies have shown promising results, a significant expansion of their clinical use will require collaborative efforts to elucidate resistance mechanisms, exploit tumor sensitivity, map cancer dependence, discover new targets, identify predictive biomarkers, evaluate combination therapies, and develop real-time monitoring approaches. Leveraging cutting-edge multi-disciplinary team approaches, we will support the NCI Drug Resistance and Sensitivity Network (DRSN) to understand and combat mechanisms of tumor resistance and to exploit tumor sensitivity to anti-cancer therapies.
