Jonathan Coloff, PhD, co-leader of the University of Illinois Cancer Center Cancer Biology Research Program, is the corresponding author of a paper published in the Journal of Clinical Investigation Insight. The study, “Drug Screening in Human Physiologic Medium Identifies Uric Acid as an Inhibitor of Rigosertib Efficacy,” includes other authors in the Department of Physiology and Biophysics at the University of Illinois College of Medicine Chicago, where Coloff is an Assistant Professor, including Vipin Singh Rawat, PhD, who is mentored by Coloff and the study’s first author.
To read the full study, click the link here. The study abstract is below.
“The nonphysiological nutrient levels found in traditional culture media have been shown to affect numerous aspects of cancer cell physiology, including how cells respond to certain therapeutic agents. Here, we comprehensively evaluated how physiological nutrient levels affect therapeutic response by performing drug screening in human plasma-like medium. We observed dramatic nutrient-dependent changes in sensitivity to a variety of FDA-approved and clinically trialed compounds, including rigosertib, an experimental cancer therapeutic that recently failed in phase III clinical trials. Mechanistically, we found that the ability of rigosertib to destabilize microtubules is strongly inhibited by the purine metabolism end product uric acid, which is uniquely abundant in humans relative to traditional in vitro and in vivo cancer models. These results demonstrate the broad and dramatic effects nutrient levels can have on drug response and how incorporation of human-specific physiological nutrient medium might help identify compounds whose efficacy could be influenced in humans.”