Cancer Cell Genomics, Signaling, and Metastasis Research Program

CANCER CELL GENOMICS, SIGNALING, AND METASTASIS (CGSM): ABSTRACT The Cancer Cell Genomics, Signaling, and Metastasis (CGSM) Research Program serves as a “discovery science engine and catalyst” within Mayo Clinic Comprehensive Cancer Center (MCCCC) to drive innovative science and translation that are responsive to the needs of the patients and communities served by Mayo Clinic. Co-led by Mark McNiven (MCR), Panos Anastasiadis (MCF), Zhenkun Lou (MCR), and with community input facilitated by the MCCCC Community Outreach and Engagement Office (COE), CGSM has contributed significantly to our basic understanding of how cells undergo cancer transformation and how targeting these processes can be exploited for intervention. The CGSM Program will provide new insights into these processes while driving the science and its clinical applications through collaboration with other MCCCC Research Programs. These actions are coordinated with COE, Cancer Research Training and Education Coordination Office (CRTEC), and the Disease Groups (DGs), while leading the training and educating of a spectrum of learners. With reorganization of the MCCCC Research Programs, CGSM has become the primary engine of basic discovery to translational science in the Center with 57 members (44 MCR, 4 MCA, and 9 MCF) from 17 departments. Significant accomplishments include 74 peer-reviewed cancer relevant projects and active leadership in four NCI-supported SPORE Programs (Breast, Ovarian, Multiple Myeloma, and Hepatobiliary). CGSM has made numerous important cancer-related findings. Two seminal examples are defining a mechanism of BRCA1-BARD1 recruitment to damaged chromatin (Leland Hu et al, Nature 2021), and senescence promoting early-stage Kras-driven lung tumorigenesis (Luis Prieto et al, Cancer Cell 2023). CGSM continues to pursue our Central Hypothesis that malignancy-associated alterations in the cellular genome, signaling cascades, and surrounding environment act synergistically to amplify tumor growth, progression, and dissemination. Our four Specific Aims include studies of: 1) DNA replication and repair dysregulation and cell cycle control; 2) cancer genomics and epigenomics focused on genetic alterations that contribute to cancer development and progression; 3) tumor cell metabolism and signaling pathways that contribute to cancer cell growth; and 4) the tumor microenvironment and stromal remodeling that contribute to cancer invasion and metastasis. CGSM currently holds $11.1M in annual peer-reviewed funding (direct costs), of which $7.7M (69%) is from NCI, a significant increase compared to $5.6M in annual peer-reviewed NCI funding in 2018. From 2019-2023, CSGM published 772 peer-reviewed cancer-related publications: 12% intra-programmatic, 47% inter-programmatic, 41% were collaborative with other National Cancer Institute (NCI) Centers, and 44% had impact factors ≥10. Our current and future strategic plans are to continue to pursue impactful and innovative, cancer-focused, discovery science with new initiatives that will expand our presence in the structural biology of cancer relevant protein-nucleotide complexes and the biology of cellular senescence in cancer initiation and growth.