An NCI-designated Comprehensive Cancer Center
By Katie Neith | January 7, 2020
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When exploring and developing new therapies for diseases like cancer and diabetes, there can often be a significant lag time between a breakthrough at the bench and being able to apply successful study results to patients in need. Luckily at City of Hope, the Drug Discovery and Structural Biology (DDSB) Core exists to bridge that gap and help speed the translation of basic science discoveries into the clinic.
Despite the recent advances in treating cancer and diabetes over the last decade, many current therapies could be improved upon for better efficacy and less toxicity. In addition, there remains many disease states that urgently require new therapies.
“There are cancers that have recurred or become refractory to known treatments for which no good options are available,” explains David Horne, Ph.D., vice provost and associate director of Beckman Research Institute at City of Hope and the Dr. & Mrs. Allen Y. Chao Chair in Developmental Cancer Therapeutics. “The DDSB core facilitates the development of novel therapies to treat such conditions.”    
The DDSB core, which Horne co-directs with John Williams, Ph.D., professor of molecular medicine, is one of City of Hope’s National Cancer Institute-Designated Comprehensive Cores that supports the research activities of investigators from not only the cancer center and but also the Diabetes and Metabolism Research Institute. Fundamental to the DDSB core is the design and development of new targeted therapeutics ranging from small molecules to antibodies and therapeutic oligonucleotides.    
Horne points out that the DDSB core is also essential for the development and advancement of projects in critical areas like the Preclinical Drug Development Venture at City of Hope and the Hope Portfolio Fund pipeline, which is an internal granting initiative for translational research projects being developed for patient care and commercial availability.     
The DDSB consists of four major components that offer a wide variety of important services for City of Hope investigators and their collaborators. For example, X-ray crystallography provides researchers the ability to determine the structural characterization of drug-protein complexes at atomic resolution and high throughput screening technology provides unique opportunities for the discovery of small-molecule inhibitors of targeted proteins. Synthetic and biopolymer chemistry experts synthesize complex molecules as well as imaging agents, nanoparticles, focused combinatorial libraries, and more, while scientists in the computational therapeutics facility aid in the design of small molecule inhibitors or modulators, bioengineer better antibodies, and investigate drug-protein interactions.
Together, researchers within the core can offer a full array of early-phase drug discovery services and chemical probes for biological systems. These techniques are provided by an interdisciplinary team of biologists, structural biologists, computational chemists, and medicinal chemists that specialize in drug discovery and the translation of early stage leads into clinical drug candidates for Phase I clinical trials. The drugs are then manufactured in City of Hope’s Chemical GMP Synthesis Facility for use in the trials, closing the loop from drug discovery to manufacturing and experimentation.  
“This translational infrastructure and expertise are what distinguishes City of Hope as an academic leader in the rapid development of new therapies for urgent unmet needs,” says Horne. “The goal is to bring tomorrow’s cures to patients who need them today.”