Cancer Signaling Networks Research Program

CANCER SIGNALING NETWORKS RESEARCH PROGRAM PROGRAM CODE: CSN PROJECT SUMMARY/ABSTRACT Cancer Signaling Networks (CSN) is a transdisciplinary research program that leverages advances in knowledge of signaling networks to develop groundbreaking therapies that address clinical needs. The Program includes world-class investigators who study fundamental aspects of signaling and metabolic networks relevant to cancer and who develop novel technologies to study signaling that can be harnessed for basic and translational cancer research. CSN clinical investigators provide expertise with signaling targeting agents in the clinic and bring patient-driven perspectives to the program. CSN initiates and facilitates research activities and collaborations across three overarching programmatic synergistic themes: cancer metabolism, metastasis and drug resistance. These areas of strategic focus leverage program member’s expertise to overcome challenges in treating YCC priority cancers for our catchment area, including lung, breast, prostate and liver cancer that have higher (or rising) incidence in CT, and/or disproportionately affect specific populations. CSN research priorities also address disparities-associated risk factors and co-morbidities in our catchment area. These align with YCC priorities including cancers tied to metabolism (obesity and fatty/fibrotic liver syndrome- associated cancers) and tobacco use (smoking-related malignancies). CSN Aims are to: 1) Elucidate intra- cellular signaling and metabolic networks that contribute to cancer; 2) Understand how cells communicate with one another and with the microenvironment during malignant progression; and 3) Exploit this knowledge to identify new therapeutic targets, improve impact of existing agents, and overcome treatment resistance. In pursuit of our Aims, CSN investigators pioneer cutting edge spatial profiling technologies, sensitive biomarker assays, and novel model systems. With our efforts to assemble unique biorepositories of patient specimens, we are well positioned to enable further high-impact discoveries. CSN has 51 members from 16 different Yale departments. Funding is robust, with total cancer-focused funding of $12.9M (direct costs) including $9.8M in peer-reviewed funding, $4.0M from the NCI. Program members published 399 papers during this award period of which 44% are high impact and include both inter-programmatic (37%) and intra-programmatic (14%) collaborations. We are focused on expanding intra-programmatic collaborations in strategic areas, an effort which has recently yielded multi-PI grants – with others being submitted. CSN members also lead training and mentorship initiatives for the next generations of cancer researchers. Finally, since the last cycle, CSN members play key roles in the Yale SPOREs and provide leadership on clinical trials. CSN members are also involved in vigorous inter-programmatic collaborations – most notably with Developmental Therapeutics (DT) – to promote efficient and effective translation of CSN science. With its translational and clinical expertise, CSN has successfully moved discoveries to the clinic during the last funding cycle and incorporated research relevant to clinical observations into its portfolio, a strength it will continue to exert in the next project period.