Abstract
The tumor immune microenvironment is rapidly emerging as a key determinant in tumor progression, response to therapy, and ultimate prognosis. The intricate role immune components, in the field-accepted “Hallmarks of Cancer”, play in malignant cell growth are becoming better understood. Specifically, the crosstalk between the innate immune system and the tumor microenvironment influence the polarization from tumor promoting to tumor suppressive. Our previous work in this area has focused on mechanisms of action studies using small molecule inhibitors derived from nucleosides and peptides. Our approach to drug discovery in oncology is built on a fundamental analysis of basic biochemical and biophysical processes in normal vs. diseased state for initiation of a drug discovery campaign against a given putative target. Our approach is inherently interdisciplinary, allowing for the development of novel, functional High-throughput screens, artificial intelligence-driven computational modeling, and synthesis of novel chemical matter. Herein, three separate drug discovery initiatives are highlighted, summarizing the previous 5 years of productivity in the field of cancer biology.
The programs focus on epigenetic modulation through DNMT1 inhibition, PD-1 checkpoint blockade, and GLI1 transcription factor inhibition to affect the immunosuppressive microenvironment that often renders a cancer resistant to both chemo- and immune-therapies. We are continuing to build on our understanding of fluidity of the composition and contribution within the tumor environment to uncover vulnerabilities in the plasticity of the microenvironment. The contributions of the tumor microenvironment can be distilled to the promotors of the resident suppressive tumor immune cells. Whether this is driven by opportunistic bacteria, aberrant transcription factor signaling from the cancer cells, epigenetic modulation, over production of immune checkpoint promotors, or other factors is to be determined. The goal of the proposed work is to understand the fundamental interplay of these biochemical functions to identify critical cells, pathways and proteins as vulnerabilities for therapeutic intervention.
Speaker
Rebecca Boohaker, Ph.D.
Director of Oncology
Boohaker is the study director for Southern Research’s oncology department. She designs, oversees, executes and interprets all cancer-related in vivo studies to evaluate potential cancer treatments, including cancer-fighting viruses and other agents that might help combat the disease. Trained primarily as a molecular biologist, Boohaker’s graduate work at the University of Central Florida resulted in a targeted peptide therapy to combat triple negative breast cancer. Since joining Southern Research, her recent work has focused on chemo-resistant colorectal cancers as well as pancreatic cancers. Boohaker received a bachelor’s degree in biology from the University of Alabama at Birmingham and a doctorate in biomedical sciences from the University of Central Florida. Her postdoctoral work at Southern Research focused on cancer biology and DNA damage repair.
