Posted May 13, 2014
Dr. Ching-Shih Chen, Ohio State University
Many current chemotherapy treatments for prostate cancer work by blocking the activity of the Androgen Receptor (AR). Unfortunately, this form of treatment can also result in the development of advanced disease that no longer responds to the same androgen blocking treatments, resulting in a much more severe form of the disease that is often fatal. Therefore many researchers are attempting to discover new chemotherapy agents that target the androgen receptor through a different mechanism. With the support of a 2008 Idea Development Award, Dr. Ching-Shih Chen and his group at the Ohio State University wanted to investigate the possibility that the production of androgen receptor could be targeted by blocking an alternative pathway - glucose metabolism.
Previous studies had shown that agents mimicking glucose restriction, such as 2-deoxyglucose (2-DG), can reduce prostate cancer cell growth in vitro and in animal models. Therefore, Dr. Chen wanted to develop new agents to inhibit glucose transportation and activate a starvation response in the cancer cells. His PCRP-funded work demonstrated in xenograft mouse models that the CG-5 agent was capable of eliciting the starvation-associated response in prostate cancer cells, and that this response was tumor cell-specific since normal prostate cells were shown to be resistant to the drug. Importantly, the CG-5 agents also appeared to be non-toxic, an important characteristic for agents with clinical potential.
Dr. Chen and his group have shown the potential of CG-5 as a therapeutic agent, and validated their hypothesis that AR expression can be selectively targeted by blocking glucose metabolism in prostate cancer cells. Continued optimization of the CG-5 agent is currently underway in Dr. Chen's lab with the goal of generating an optimized lead compound ready for preclinical development and eventually testing in clinical trials.