Matthew Kalady, MD explains the importance of patient-centered research to identify novel biomarkers for radiation resistance and potential therapeutic targets. Dr. Kalady explores targeted therapies, and presents clinical algorithms and personalized approaches to care.
Hi, My name is Matt Clady. I'm the chief of the division of colon rectal surgery at the Ohio State University. I'm excited to be able to share an example of some of the research my team and I are doing as a surgeon. Scientists, patients at the center of everything we do, in particular of a clinical and academic interest in collective cancer. We're seeing some positive changes in the multiplayer treatment paradigms of rectal cancer. In general, patients undergo clinical staging, and those with locally advanced disease were referred for new agin therapy, including human radiation, and often also chemotherapy. After that, we determine the treatment response and make further treatment plans. If the patients had a complete clinical response, meaning there is no detectable residual tumor, those patients can now be offered a non operative approach, which entails active surveillance, also known as watch and wait. If there is any residual tumor, the patient goes on to surgery, and the pathologist provides a score that correlates with the amount of residual tumor. This is important because there's a large variability and how patients respond from a complete response toe. Almost none. We have previously shown that the response to you as your therapy directly correlates were survival. However, there still remains a huge knowledge gap as to why thes differences exist and also a huge clinical need to improve the overall degree of response and decrease the number of complete responders. So ultimately, we could improve survival and potentially offer non operative approach for more patients. But the big question still is. How do we get there? Help answer this. We turn to patients with rectal cancer and obtained biopsies of their tumor before starting any type of treatment. We then analyze the mRNA expression patterns for those tumors. And meanwhile, patients went on to receive the new admit therapy and surgery and then had the response scored by a pathologist. We then took the pre treatment tumor on expressions and tried to correlate those with the response patterns and identified a few key proteins that were potential targets associated with radiation resistance. The most promising protein identified is called coenzyme a synthesis or cozy. First, we valid observation with independent Marty approaching expression studies and found that there's a direct correlation with cozy levels and radiation response. We then move this information back to the bench and created knockdown sidelines and demonstrated that sells with lower levels of cozy what, more easily killed by radiation from the sidelines. We also generated Ortho topic mice models with Xena graphs and treated these tumors with radiation. And again the tumors would decrease. Cozy were much more susceptible to radiation treatment compared to controls. This effect was realized via decrease cellular proliferation, increased apoptosis and decreased DNA repair. So clearly cozy impact cell survival pathways and influences treatment effectiveness. So in summary, we have utilized patients Senate Research to identify a novel biomarker for radiation resistance and also a potential therapeutic target. We'll continue to work in the lab to unravel the mechanisms through which this works in our exploring possible targeted therapies, our goal is to be able to translate this work into a more personalized approach to patients with rectal cancer. As we continue to science and research to improve the lives and outcomes of our patients. Thank you very much for your interest in learning about our work