The interdisciplinary Chemistry and Cancer (CC) Program is uniquely situated in Simmons Comprehensive Cancer Center (SCCC) to bridge fundamental biology research with the discovery of novel therapies for the treatment of cancer. CC has facilitated numerous intraprogrammatic and interprogrammatic collaborations, which have resulted in new insights into cancer biology and drug discovery of high clinical applicability. CC combines the expertise of synthetic and medicinal chemists, molecular and structural biologists, biochemists, chemical biologists, pharmacologists, and clinician scientists to discover, design, and optimize drug-like small molecules that regulate biological pathways deregulated in cancer. CC’s discovery platform is guided by the hypothesis that an interdisciplinary and chemically focused approach to cancer biology will provide new avenues for discovery in cancer prevention and treatment. The CC Program is co-led by Jef De Brabander, PhD, and Uttam Tambar, PhD, and is composed of 22 members who are drawn from seven departments on campus. The CC Scientific Program is defined by three specific aims: (1) Identification of Molecular Targets of Novel Anti- Cancer Agents, (2) Biochemical Dissection of Regulatory Pathways Relevant to Human Cancer, and (3) Structure-Based Design of Chemicals that Perturb Cancer-Relevant Signaling Pathways. The CC Program focuses on acceleration of the continued translation of chemical discoveries made at the UT Southwestern Medical Center (UTSW) and SCCC to the clinic, the initiation of early-stage translational studies, and the licensing of mid- to late-stage preclinical studies. The CC Program will continue to prioritize research programs that impact cancers that are prevalent in the SCCC catchment area, such as colorectal, lung, kidney, and liver cancers. In addition, the CC Program will promote interprogrammatic and intraprogrammatic collaborations and explore new projects in the three specific aims. Total direct peer-reviewed funding to the CC Program is $5.2M, with $2.6M (51%) from the NCI. CC Program members have authored 253 peer-reviewed publications since 2014, of which 17% were intraprogrammatic, 40% interprogrammatic, and 36% were in journals with impact factors ≥ 10.