ResearchIn-Press PreviewCell biologyOncology Open Access | 10.1172/jci.insight.174329
1Department of Physiology and Biophysics, University of Illinois College of Medicine, Chicago, United States of America
2Department of Biomedical Engineering, The University of Michigan, Ann Arbor, United States of America
3Division of Hematology and Oncology, Vanderbilt University Medical Center, Nashville, United States of America
4Department of Nutrition and Integrative Physiology, Florida State University, Tallahassee, United States of America
5Meyer Cancer Center, Weill Cornell Medicine, New York, United States of America
6Department of Metabolism and Physiology, H. Lee Moffiitt Cancer Center, Tampa, United States of America
7Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, United States of America
8Department of Cancer Imaging and Metabolism, H. Lee Moffitt Cancer Center & Research Institute, Tampa, United States of America
9Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, United States of America
Find articles by Rawat, V. in: JCI | PubMed | Google Scholar
1Department of Physiology and Biophysics, University of Illinois College of Medicine, Chicago, United States of America
2Department of Biomedical Engineering, The University of Michigan, Ann Arbor, United States of America
3Division of Hematology and Oncology, Vanderbilt University Medical Center, Nashville, United States of America
4Department of Nutrition and Integrative Physiology, Florida State University, Tallahassee, United States of America
5Meyer Cancer Center, Weill Cornell Medicine, New York, United States of America
6Department of Metabolism and Physiology, H. Lee Moffiitt Cancer Center, Tampa, United States of America
7Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, United States of America
8Department of Cancer Imaging and Metabolism, H. Lee Moffitt Cancer Center & Research Institute, Tampa, United States of America
9Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, United States of America
Find articles by DeLear, P. in: JCI | PubMed | Google Scholar |
1Department of Physiology and Biophysics, University of Illinois College of Medicine, Chicago, United States of America
2Department of Biomedical Engineering, The University of Michigan, Ann Arbor, United States of America
3Division of Hematology and Oncology, Vanderbilt University Medical Center, Nashville, United States of America
4Department of Nutrition and Integrative Physiology, Florida State University, Tallahassee, United States of America
5Meyer Cancer Center, Weill Cornell Medicine, New York, United States of America
6Department of Metabolism and Physiology, H. Lee Moffiitt Cancer Center, Tampa, United States of America
7Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, United States of America
8Department of Cancer Imaging and Metabolism, H. Lee Moffitt Cancer Center & Research Institute, Tampa, United States of America
9Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, United States of America
Find articles by Prashanth, P. in: JCI | PubMed | Google Scholar |
1Department of Physiology and Biophysics, University of Illinois College of Medicine, Chicago, United States of America
2Department of Biomedical Engineering, The University of Michigan, Ann Arbor, United States of America
3Division of Hematology and Oncology, Vanderbilt University Medical Center, Nashville, United States of America
4Department of Nutrition and Integrative Physiology, Florida State University, Tallahassee, United States of America
5Meyer Cancer Center, Weill Cornell Medicine, New York, United States of America
6Department of Metabolism and Physiology, H. Lee Moffiitt Cancer Center, Tampa, United States of America
7Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, United States of America
8Department of Cancer Imaging and Metabolism, H. Lee Moffitt Cancer Center & Research Institute, Tampa, United States of America
9Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, United States of America
Find articles by Ozgurses, M. in: JCI | PubMed | Google Scholar |
1Department of Physiology and Biophysics, University of Illinois College of Medicine, Chicago, United States of America
2Department of Biomedical Engineering, The University of Michigan, Ann Arbor, United States of America
3Division of Hematology and Oncology, Vanderbilt University Medical Center, Nashville, United States of America
4Department of Nutrition and Integrative Physiology, Florida State University, Tallahassee, United States of America
5Meyer Cancer Center, Weill Cornell Medicine, New York, United States of America
6Department of Metabolism and Physiology, H. Lee Moffiitt Cancer Center, Tampa, United States of America
7Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, United States of America
8Department of Cancer Imaging and Metabolism, H. Lee Moffitt Cancer Center & Research Institute, Tampa, United States of America
9Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, United States of America
Find articles by Tebeje, A. in: JCI | PubMed | Google Scholar
1Department of Physiology and Biophysics, University of Illinois College of Medicine, Chicago, United States of America
2Department of Biomedical Engineering, The University of Michigan, Ann Arbor, United States of America
3Division of Hematology and Oncology, Vanderbilt University Medical Center, Nashville, United States of America
4Department of Nutrition and Integrative Physiology, Florida State University, Tallahassee, United States of America
5Meyer Cancer Center, Weill Cornell Medicine, New York, United States of America
6Department of Metabolism and Physiology, H. Lee Moffiitt Cancer Center, Tampa, United States of America
7Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, United States of America
8Department of Cancer Imaging and Metabolism, H. Lee Moffitt Cancer Center & Research Institute, Tampa, United States of America
9Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, United States of America
Find articles by Burns, P. in: JCI | PubMed | Google Scholar
1Department of Physiology and Biophysics, University of Illinois College of Medicine, Chicago, United States of America
2Department of Biomedical Engineering, The University of Michigan, Ann Arbor, United States of America
3Division of Hematology and Oncology, Vanderbilt University Medical Center, Nashville, United States of America
4Department of Nutrition and Integrative Physiology, Florida State University, Tallahassee, United States of America
5Meyer Cancer Center, Weill Cornell Medicine, New York, United States of America
6Department of Metabolism and Physiology, H. Lee Moffiitt Cancer Center, Tampa, United States of America
7Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, United States of America
8Department of Cancer Imaging and Metabolism, H. Lee Moffitt Cancer Center & Research Institute, Tampa, United States of America
9Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, United States of America
Find articles by Conger, K. in: JCI | PubMed | Google Scholar
1Department of Physiology and Biophysics, University of Illinois College of Medicine, Chicago, United States of America
2Department of Biomedical Engineering, The University of Michigan, Ann Arbor, United States of America
3Division of Hematology and Oncology, Vanderbilt University Medical Center, Nashville, United States of America
4Department of Nutrition and Integrative Physiology, Florida State University, Tallahassee, United States of America
5Meyer Cancer Center, Weill Cornell Medicine, New York, United States of America
6Department of Metabolism and Physiology, H. Lee Moffiitt Cancer Center, Tampa, United States of America
7Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, United States of America
8Department of Cancer Imaging and Metabolism, H. Lee Moffitt Cancer Center & Research Institute, Tampa, United States of America
9Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, United States of America
Find articles by Solís, C. in: JCI | PubMed | Google Scholar
1Department of Physiology and Biophysics, University of Illinois College of Medicine, Chicago, United States of America
2Department of Biomedical Engineering, The University of Michigan, Ann Arbor, United States of America
3Division of Hematology and Oncology, Vanderbilt University Medical Center, Nashville, United States of America
4Department of Nutrition and Integrative Physiology, Florida State University, Tallahassee, United States of America
5Meyer Cancer Center, Weill Cornell Medicine, New York, United States of America
6Department of Metabolism and Physiology, H. Lee Moffiitt Cancer Center, Tampa, United States of America
7Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, United States of America
8Department of Cancer Imaging and Metabolism, H. Lee Moffitt Cancer Center & Research Institute, Tampa, United States of America
9Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, United States of America
Find articles by Hasnain, Y. in: JCI | PubMed | Google Scholar
1Department of Physiology and Biophysics, University of Illinois College of Medicine, Chicago, United States of America
2Department of Biomedical Engineering, The University of Michigan, Ann Arbor, United States of America
3Division of Hematology and Oncology, Vanderbilt University Medical Center, Nashville, United States of America
4Department of Nutrition and Integrative Physiology, Florida State University, Tallahassee, United States of America
5Meyer Cancer Center, Weill Cornell Medicine, New York, United States of America
6Department of Metabolism and Physiology, H. Lee Moffiitt Cancer Center, Tampa, United States of America
7Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, United States of America
8Department of Cancer Imaging and Metabolism, H. Lee Moffitt Cancer Center & Research Institute, Tampa, United States of America
9Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, United States of America
Find articles by Novikova, A. in: JCI | PubMed | Google Scholar
1Department of Physiology and Biophysics, University of Illinois College of Medicine, Chicago, United States of America
2Department of Biomedical Engineering, The University of Michigan, Ann Arbor, United States of America
3Division of Hematology and Oncology, Vanderbilt University Medical Center, Nashville, United States of America
4Department of Nutrition and Integrative Physiology, Florida State University, Tallahassee, United States of America
5Meyer Cancer Center, Weill Cornell Medicine, New York, United States of America
6Department of Metabolism and Physiology, H. Lee Moffiitt Cancer Center, Tampa, United States of America
7Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, United States of America
8Department of Cancer Imaging and Metabolism, H. Lee Moffitt Cancer Center & Research Institute, Tampa, United States of America
9Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, United States of America
Find articles by Endress, J. in: JCI | PubMed | Google Scholar
1Department of Physiology and Biophysics, University of Illinois College of Medicine, Chicago, United States of America
2Department of Biomedical Engineering, The University of Michigan, Ann Arbor, United States of America
3Division of Hematology and Oncology, Vanderbilt University Medical Center, Nashville, United States of America
4Department of Nutrition and Integrative Physiology, Florida State University, Tallahassee, United States of America
5Meyer Cancer Center, Weill Cornell Medicine, New York, United States of America
6Department of Metabolism and Physiology, H. Lee Moffiitt Cancer Center, Tampa, United States of America
7Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, United States of America
8Department of Cancer Imaging and Metabolism, H. Lee Moffitt Cancer Center & Research Institute, Tampa, United States of America
9Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, United States of America
Find articles by González-Sánchez, P. in: JCI | PubMed | Google Scholar
1Department of Physiology and Biophysics, University of Illinois College of Medicine, Chicago, United States of America
2Department of Biomedical Engineering, The University of Michigan, Ann Arbor, United States of America
3Division of Hematology and Oncology, Vanderbilt University Medical Center, Nashville, United States of America
4Department of Nutrition and Integrative Physiology, Florida State University, Tallahassee, United States of America
5Meyer Cancer Center, Weill Cornell Medicine, New York, United States of America
6Department of Metabolism and Physiology, H. Lee Moffiitt Cancer Center, Tampa, United States of America
7Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, United States of America
8Department of Cancer Imaging and Metabolism, H. Lee Moffitt Cancer Center & Research Institute, Tampa, United States of America
9Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, United States of America
Find articles by Dong, W. in: JCI | PubMed | Google Scholar
1Department of Physiology and Biophysics, University of Illinois College of Medicine, Chicago, United States of America
2Department of Biomedical Engineering, The University of Michigan, Ann Arbor, United States of America
3Division of Hematology and Oncology, Vanderbilt University Medical Center, Nashville, United States of America
4Department of Nutrition and Integrative Physiology, Florida State University, Tallahassee, United States of America
5Meyer Cancer Center, Weill Cornell Medicine, New York, United States of America
6Department of Metabolism and Physiology, H. Lee Moffiitt Cancer Center, Tampa, United States of America
7Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, United States of America
8Department of Cancer Imaging and Metabolism, H. Lee Moffitt Cancer Center & Research Institute, Tampa, United States of America
9Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, United States of America
Find articles by Stephanopoulos, G. in: JCI | PubMed | Google Scholar
1Department of Physiology and Biophysics, University of Illinois College of Medicine, Chicago, United States of America
2Department of Biomedical Engineering, The University of Michigan, Ann Arbor, United States of America
3Division of Hematology and Oncology, Vanderbilt University Medical Center, Nashville, United States of America
4Department of Nutrition and Integrative Physiology, Florida State University, Tallahassee, United States of America
5Meyer Cancer Center, Weill Cornell Medicine, New York, United States of America
6Department of Metabolism and Physiology, H. Lee Moffiitt Cancer Center, Tampa, United States of America
7Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, United States of America
8Department of Cancer Imaging and Metabolism, H. Lee Moffitt Cancer Center & Research Institute, Tampa, United States of America
9Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, United States of America
Find articles by DeNicola, G. in: JCI | PubMed | Google Scholar
1Department of Physiology and Biophysics, University of Illinois College of Medicine, Chicago, United States of America
2Department of Biomedical Engineering, The University of Michigan, Ann Arbor, United States of America
3Division of Hematology and Oncology, Vanderbilt University Medical Center, Nashville, United States of America
4Department of Nutrition and Integrative Physiology, Florida State University, Tallahassee, United States of America
5Meyer Cancer Center, Weill Cornell Medicine, New York, United States of America
6Department of Metabolism and Physiology, H. Lee Moffiitt Cancer Center, Tampa, United States of America
7Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, United States of America
8Department of Cancer Imaging and Metabolism, H. Lee Moffitt Cancer Center & Research Institute, Tampa, United States of America
9Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, United States of America
Find articles by Harris, I. in: JCI | PubMed | Google Scholar
1Department of Physiology and Biophysics, University of Illinois College of Medicine, Chicago, United States of America
2Department of Biomedical Engineering, The University of Michigan, Ann Arbor, United States of America
3Division of Hematology and Oncology, Vanderbilt University Medical Center, Nashville, United States of America
4Department of Nutrition and Integrative Physiology, Florida State University, Tallahassee, United States of America
5Meyer Cancer Center, Weill Cornell Medicine, New York, United States of America
6Department of Metabolism and Physiology, H. Lee Moffiitt Cancer Center, Tampa, United States of America
7Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, United States of America
8Department of Cancer Imaging and Metabolism, H. Lee Moffitt Cancer Center & Research Institute, Tampa, United States of America
9Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, United States of America
Find articles by Sept, D. in: JCI | PubMed | Google Scholar
1Department of Physiology and Biophysics, University of Illinois College of Medicine, Chicago, United States of America
2Department of Biomedical Engineering, The University of Michigan, Ann Arbor, United States of America
3Division of Hematology and Oncology, Vanderbilt University Medical Center, Nashville, United States of America
4Department of Nutrition and Integrative Physiology, Florida State University, Tallahassee, United States of America
5Meyer Cancer Center, Weill Cornell Medicine, New York, United States of America
6Department of Metabolism and Physiology, H. Lee Moffiitt Cancer Center, Tampa, United States of America
7Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, United States of America
8Department of Cancer Imaging and Metabolism, H. Lee Moffitt Cancer Center & Research Institute, Tampa, United States of America
9Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, United States of America
Find articles by Mason, F. in: JCI | PubMed | Google Scholar |
1Department of Physiology and Biophysics, University of Illinois College of Medicine, Chicago, United States of America
2Department of Biomedical Engineering, The University of Michigan, Ann Arbor, United States of America
3Division of Hematology and Oncology, Vanderbilt University Medical Center, Nashville, United States of America
4Department of Nutrition and Integrative Physiology, Florida State University, Tallahassee, United States of America
5Meyer Cancer Center, Weill Cornell Medicine, New York, United States of America
6Department of Metabolism and Physiology, H. Lee Moffiitt Cancer Center, Tampa, United States of America
7Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, United States of America
8Department of Cancer Imaging and Metabolism, H. Lee Moffitt Cancer Center & Research Institute, Tampa, United States of America
9Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, United States of America
Find articles by Coloff, J. in: JCI | PubMed | Google Scholar
Published May 30, 2024 - More info
The non-physiological 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 impact therapeutic response by performing drug screening in human plasma-like medium (HPLM). 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 has recently failed in phase 3 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 media might help to identify compounds whose efficacy could be impacted in humans.