CANCER BIOLOGY (CBIO) – PROJECT SUMMARY/ABSTRACT A critical need remains for new therapies to treat various types of cancer. The discovery of new therapies begins with uncovering the basic mechanisms that drive cancer, identifying the critical components of those mechanisms, and then subsequently targeting them with small molecules that act as drugs for cancer therapy. The Cancer Biology (CBIO) program exists to unite University of Virginia Cancer Center (UVACC) investigators whose research programs collectively make discoveries about mechanisms that drive cancer and advance that knowledge through to the identification of therapeutic targets and development of small molecule modulators to interfere with these targets. The CBIO program has a robust research base of investigators working to elucidate mechanisms driving cancer, particularly with respect to how various signaling networks contribute to tumor initiation and metastasis (Aim 1) and to validate individual proteins in tumors as targets for small molecule modulators and identify or develop small molecule modulators of validated targets in cancers (Aim 2). Investigators work to develop an understanding about how receptors and intracellular signaling support homeostasis in normal tissues and how mutations perturb these networks. These efforts are critical to identify pathways that represent vulnerabilities in particular cancers leading to new targets for validation and development of small molecule modulators. The identification of novel targets feeds subsequent efforts to move small molecule therapeutics further along the pipeline toward clinical application in conjunction with the Cancer Therapeutics Program (CRX). The CBIO program has two co-leaders: Bushweller leverages his expertise in chemical and structural biology within the Program to support and enhance cancer research; Gioeli's experience in industry developing a novel pre-clinical model for target identification, validation, and drug discovery enables him to support CBIO Program goals. The Program consists of 53 members, 17 of whom are new to UVA or the UVACC, from 10 departments and three schools. The Program Members are principal investigators of grants totaling $12.83M of current direct cost peer-reviewed funding with $3.29M from NCI and $9.54M from other agencies. Twelve CBIO Program Members participate in one or more of the disease-specific Translational Research Teams, which were created to spawn research in cancers that are over-represented in the UVACC catchment area; three CBIO members serve as basic science co-leaders, thus leveraging basic science expertise to advance research in cancers of particular relevance. CBIO Members depend on the Shared Resources provided by the UVACC, particularly the Advanced Microscopy Facility, the Biomolecular Analysis Facility, the Biorepository and Tissue Research Facility, and the Flow Cytometry Core. Together, these activities culminated in 236 selected publications since the last gra...