PROJECT SUMMARY The Cancer Biology and Cancer Stem Cells (CB) Program is a basic and translational science program that aims to understand the fundamental mechanisms underlying cancer development. From these insights, we aspire to improve cancer diagnosis and treatment through the following specific aims: (1) understand the regulation and function of normal and cancer stem cells, (2) understand the mechanisms of initiation and progression of epithelial cancers, and (3) identify potential new therapeutic targets. The program is co-led by Laura Attardi, PhD, and Roeland Nusse, PhD. In 2019, the former Cancer Biology Program and Cancer Stem Cells Program merged with the approval of the EAB to become the current Cancer Biology and Cancer Stem Cells Program. In the current funding period, program members have made substantial progress in understanding the self-renewal pathways of cancer stem cells and in elucidating signaling pathways of high cancer relevance, including most prominently the Wnt and Hedgehog pathways. They have also pioneered a new technology, ATAC-seq, that enables a more fundamental understanding of the role of chromatin in gene expression and used organoid and mouse model systems to discover the mechanisms of tumor suppressors and progression and to uncover new therapeutic targets. The 53 members of the current program represent 16 departments within the Schools of Medicine (SOM), Humanities and Sciences, and Engineering. Members are supported by peer-reviewed research totaling $25.6M, including 34 R01s, 12 R35s, 6 U01s, and 3 T32s. Peer-reviewed cancer-focused research funding consists of $7M from the NCI, $12M from other NIH sources, and $6.6M from other peer-reviewed sources. The members of this program are highly motivated and interactive in their goal to use basic science approaches to understand cancer initiation and progression, with the ultimate aim of improving cancer diagnosis and treatment. Since 2015, members of the CB Program have published 668 manuscripts. Of these, 16% represent intra-programmatic, 31% represent inter-programmatic, and 95% multi-institutional collaborations, 43% and 33% are in journals with IF>10 and IF>20, respectively. The Stanford Cancer Institute (SCI) enhances the program’s goals by providing state-of-the-art shared resources, seed grant support for new projects, programmatic funds, retreats, special seminars, support for new faculty recruitments, and clinical trial infrastructure for translation of research findings. The support from the SCI has also been instrumental in promoting both intra- and inter-programmatic collaborations through organizing programmatic and working group meetings and providing the means to interface with the more clinically oriented programs to enhance our translational impact. Future plans incluce to further enhance intra- and inter- progammtic collaborations by enhance cancer focused working groups.