Precision Cancer Medicine and Investigational Therapeutics

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ABSTRACT – SOLID TUMOR THERAPEUTICS PROGRAM The Duke Cancer Institute’s Solid Tumor Therapeutics Program (STT) focuses on disease-specific drug development and testing in the following disease groups: gastrointestinal cancers (esophageal, gastric, small intestine, colorectal, anal, hepatobiliary and pancreatic), genitourinary cancers (kidney, bladder, prostate, testicular), thoracic cancers (lung), sarcoma, melanoma and head and neck cancers. Most solid tumors share common alterations in the major signaling pathways regulating development and homeostasis, including the EGF, TGF-β, PDGF, VEGF, FGFR, IGF, Hh, Wnt, Src and c-Met pathways. In addition, solid tumors share conserved roles for the tumor microenvironment (i.e., immune system, angiogenesis). Further, gaining insight into the cancer cell autonomous and tumor microenvironment alterations that will result in improvements in clinical practice requires the development of more relevant pre-clinical models to execute co-clinical trials. Accordingly, the Program’s overarching goal is to increase disease-specific drug development and testing with investigator-initiated trials based on the early stage drug discovery and lead development efforts at Duke University. The STT theme is to align the research efforts across these disease sites to increase disease-specific investigator initiated clinical trials. STT is organized into three focus groups: Signal Transduction Pathways, Tumor Microenvironment/Immunotherapy, and Preclinical Modeling. These efforts will enable us to leverage early stage drug discovery and lead development efforts at Duke, and increase disease-specific drug development and testing with investigator-initiated trials, including Phase I experimental therapeutics. Close collaboration with the Cancer Control and Population Sciences Program and Office of Health Equity also enables race-stratified clinical trials and assessing of cancer healthcare delivery measures including cost and health economics, and outcomes including patient-reported outcomes, quality and value-base care, and cancer disparities. Opportunities for translational and clinical trial development will occur through the NCI Experimental Therapeutics Clinical Trials Network with Phase I emphasis (ET-CTN) grant and the National Clinical Trials Network (NCTN) lead academic site grant, both of which are led by investigators in this Program. STT is comprised of 60 primary members and 26 secondary members from 12 different departments in 3 schools within Duke University. Total funding for primary program members is $20M, of which $4.4M is peer reviewed, including $1.8M from the NCI. From 2014-2018, Program members published 1,395 papers in peer- reviewed journals, 33% were intra-programmatic and 39% were inter-programmatic collaborations. During the current grant period, the Program enrolled 3,823 subjects to all trials, 2,216 to interventional trials, and 1,516 to treatment trials.