In the relentless pursuit of effective cancer treatments, researchers strive to understand the complex interactions between drugs, cancer cells, and the human body.
Assistant Professor Christopher Solís participated in a research team based out of the University of Illinois to shed light on how important the body’s nutrient environment is to the efficacy of cancer drugs. The study, titled “Drug screening in human physiologic medium identifies uric acid as an inhibitor of rigosertib efficacy,” was published in JCI Insight.
The first step in testing new therapeutic drugs is to screen for its effectiveness in a cell culture. Another component in drug screens is the cell media, which are solutions used in laboratories to grow and maintain cells. These media provide essential nutrients like sugars, amino acids, vitamins, and minerals necessary for cell survival and growth. They are typically used to cultivate bacteria, fungi, plant cells, or animal cells under controlled conditions.
However, traditional culture media often do not fully and accurately replicate the nutrient composition found in the human body. Therefore, they can produce distorted drug responses. Similarly, animal models don’t fully mimic the physiology of the human body. This discrepancy can lead to inconsistencies between laboratory and clinical results, Solís and his team note.
The research team specifically focused on the prospective leukemia drug Rigosertib, which recently failed in phase III clinical trials. Typically, the main goal of phase III trials is to confirm that a drug is safe, effective, and works well for treating a specific condition. The research team investigated why these trials indicated that Rigosertib drug was ineffective as a cancer therapy in humans.
“Uric acid levels are much higher in humans than they are in animal models,” Solís explained. “Uric acid is a metabolite, or the aftermath of our bodies using nutrients.”
The team’s study found that uric acid, typically excreted in urine, interfered with the drug, rendering it ineffective.
“Of course, scientists did studies in cell lines and cell media—and the drug worked in animal models—but they didn’t have the human levels of uric acid because traditional cell media is a very simplified mix of nutrients and doesn’t include metabolites or waste products from the human body; and uric acid is uniquely abundant in humans compared to other models.”
To address this, the team proposed using human plasma-like mediums (HPLMs) when testing therapeutic drugs. HPLMs are both more complex, and more reflective of the composition of human fluids such as blood plasma and interstitial fluid, or fluid inside the organs.
"Our study shows how human-specific nutrient environments can reveal novel insights into cancer drug responses. By bridging the gap between laboratory models and human physiology, we can better predict therapeutic outcomes and advance personalized medicine,” he added.
The team notes that it can be especially important and relevant when testing cancer drugs. Tumor growth is influenced by both internal and external factors, and the availability of nutrients is increasingly recognized as a key environmental factor affecting how tumors grow and thrive.
By considering the human body’s nutrient environment in drug testing, researchers hope to accelerate the discovery of effective cancer treatments tailored specifically to human biology.
The research in this study was funded by the National Institutes of Health National Cancer Institute (K22 CA215828 & R37 CA251216 to JLC; R37 CA230042 to GMD) and the Department of Defense (W81XWH2110786 to FMM).
Solís is an assistant professor in the Department of Health, Nutrition, and Food Science within the College of Education, Health, and Human Sciences. To learn more about his research, visit his faculty bio or solislab.create.fsu.edu.
Solís also recently co-authored a study analyzing trends and disparities in NIH funding for early-career scientists published in eLife.
Rawat, V., DeLear, P., Prashanth, P., Ozgurses, M. E., Tebeje, A., Burns, P. A., Conger, K. O., Solís, C., Hasnain, Y., Novikova, A., Endress, J. E., González-Sánchez, P., Dong, W., Stephanopoulos, G., DeNicola, G. M., Harris, I., Sept, D., Mason, F. M., & Coloff, J. L. (2024). Drug screening in human physiologic medium identifies uric acid as an inhibitor of rigosertib efficacy. JCI insight, e174329. Advance online publication. https://doi.org/10.1172/jci.insight.174329
Woitowich, N. C., Hengel, S. R., Solis, C., Vilgalys, T. P., Babdor, J., & Tyrrell, D. J. (2024). Analysis of NIH K99/R00 awards and the career progression of awardees. eLife, 12, RP88984. https://doi.org/10.7554/eLife.88984
