Molecular and Cellular Oncology Program

ABSTRACT Overview and Goals: The goal of the Molecular and Cellular Oncology (MCO) program is to perform in-depth mechanistic studies in pursuit of critical basic science knowledge that can be applied towards effective cancer prevention, diagnosis, and treatment. The expertise of program members is broad and deep, with major strengths in genome instability, gene expression and epigenetic regulation, DNA damage responses, telomeres, pathways controlling cell fate, and elucidation of cancer-relevant molecular structures. Research Highlights: Bench-to- bedside team science uncovered metabolic vulnerabilities of leukemia stem cells and contributed to a new therapy combination of BCL-2 inhibitor Venetoclax with standard chemotherapy that produces deep and durable remissions (Cancer Cell, 2018 [1,2]; Nature Medicine, 2018 [3]) and the finding that adding autophagy inhibitor chloroquine to BRAF inhibitor vemurafenib reduced inhibitor resistance for brain cancer patients (Elife, 2017 [4]; PNAS, 2018 [5]). Program Activities: To accomplish its goals, MCO co-leaders employ resources provided by the University of Colorado Cancer Center (UCCC) to encourage and enable intra- and inter-programmatic collaborations through organization of annual retreats and technology forums as well as fostering transdisciplinary collaborations. Assisted by UCCC support, the co-leaders catalyze new research by MCO members through the creation and expansion of Shared Resources (SR), by providing pilot funding to use these technologies, while leveraging resources and research strengths of collaborating institutions. Through coordinated transdisciplinary collaborations between MCO members and translational/clinical research programs, the discoveries made in MCO move from bench to preclinical investigations and clinical trials, which ultimately improve diagnosis, treatment, and prevention of cancer. Members: The program has 56 full and 13 mentored members with $ 4.7M NCI and $9.0M of other cancer peer-reviewed research funding. Members are from 13 basic science and clinical departments at UCAMC, UCB, CSU and National Jewish Health (NJH). Since July 2016, MCO members published 476 cancer-focused publications, of which 245 (51%) were either inter-programmatic (45%), intra- programmatic (17%), or both (11%); (27%) were in journals with an IF ≥10; and 130 (27%) represented collaborations with investigators at other NCI cancer centers. Future Directions: Through retreats/forums, seed grants, and support of relevant SRs, MCO plans to enhance current strengths in the cross-cutting research themes cancer and metabolism and cancer and aging. To promote collaborative translational research of relevance to the catchment, MCO members are collaborating with the UCCC Office of Community Outreach and Engagement to mine patient databases from the Colorado Center for Personalized Medicine for cancer-relevant genomic information in underserved populations in Colorado. Findings will be shared with MCO members to stimulate catchment-relevant cancer research. These efforts will advance the discovery of basic cancer processes and their translation into improved cancer prevention and treatment.