In silico drug discovery of dual inhibitors of combinatorial synthetic lethality inhibitors in the era of prevision medical oncology; proof of concept
Donald Durden, MD, PhD UC San Diego Moores Cancer Center
Donald Durden, MD, PhD Professor, Department of Pediatrics
Associate Director for Pediatric Hematology-Oncology
UC San Diego Moores Cancer Center
Dr. Durden’s laboratory is interested in understanding the fundamental mechanisms by which signals are transmitted from cell surface receptors to the cytoplasm and nucleus. His efforts are focused on the role of lipid and protein phosphorylation and dephosphorylation in the regulation of signal transduction and epigenetic effector mechanisms. In this regard, he is primarily interested in the regulation of signal transduction pathways in mammalian cells which might encode pathophysiologic states in pediatrics. More recently Dr. Durden has focused on the study of the epigenetic mechanisms that regulate important mammalian signaling events the immune system and oncogenesis. He is interested in converting target discovery and validation into drug discovery and drug development in particular as it relates to specific kinases and/or epigenetic effectors and translating this basic science information from "bench to bedside” in pediatric medicine. This includes hematologic, immunologic and oncologic diseases in his subspecialty and other disease processes outside of this clinical specialty area e.g. fibrosis, microbiome and infectious diseases, etc. To this end, Dr. Durden’s laboratory in collaboration with SignalRx Pharmaceuticals chemists has used in silico rational drug discovery to design and synthesize nM potent dual and triple inhibitory chemotypes against dominant synthetic lethalities and highly synergistic immune-oncology targets in an effort to develop novel safe and efficacious combinatorial therapeutic agents for cancer and other diseases.
Finally, as a board certified practicing attending pediatric hematologist-oncologist at UCSD, Dr. Durden is actively involved in the development and execution of Phase I and Phase II clinical trials of targeted and immunotherapies in cancer patients at the UCSD/Rady Children’s Hospital and Moores Cancer Center and participation in weekly molecular tumor boards. He understands the potential challenges to drug development in the pediatric population including but not restricted to cancer. He hopes to apply these combinatorial dual and triple inhibitory chemotypes in a precision medicine, genomics setting of adult and pediatric cancer.
