Evidence map›Paper›PMID 37546939›Full record

ArticlebioRxiv : the preprint server for biology2023

Drug screening in human physiologic medium identifies uric acid as an inhibitor of rigosertib efficacy.

Vipin Rawat, Patrick DeLear, Prarthana Prashanth, Mete Emir Ozgurses, Anteneh Tebeje, Philippa A Burns, Kelly O Conger, Christopher Solís, Yasir Hasnain, Anna Novikova and 9 more

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed, 2 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors at 8 institutions in 1 country.

Vipin RawatDepartment of Physiology and Biophysics, University of Illinois College of Medicine, University of Illinois Cancer Center, Chicago, IL.
Patrick DeLearDepartment of Biomedical Engineering, University of Michigan, Ann Arbor, MI.
Prarthana PrashanthDepartment of Physiology and Biophysics, University of Illinois College of Medicine, University of Illinois Cancer Center, Chicago, IL.
Mete Emir OzgursesDepartment of Physiology and Biophysics, University of Illinois College of Medicine, University of Illinois Cancer Center, Chicago, IL.
Anteneh TebejeDivision of Hematology and Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN.
Philippa A BurnsDepartment of Physiology and Biophysics, University of Illinois College of Medicine, University of Illinois Cancer Center, Chicago, IL.
Kelly O CongerDepartment of Physiology and Biophysics, University of Illinois College of Medicine, University of Illinois Cancer Center, Chicago, IL.
Christopher SolísDepartment of Nutrition and Integrative Physiology, Florida State University, Tallahassee, FL.
Yasir HasnainDepartment of Physiology and Biophysics, University of Illinois College of Medicine, University of Illinois Cancer Center, Chicago, IL.
Anna NovikovaDepartment of Physiology and Biophysics, University of Illinois College of Medicine, University of Illinois Cancer Center, Chicago, IL.
Jennifer E EndressMeyer Cancer Center, Weill Cornell Medicine, New York, NY.
Paloma González-SánchezDepartment of Metabolism and Physiology, H. Lee. Moffitt Cancer Center, Tampa, FL.
Wentao DongDepartment of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA.
Greg StephanopoulosDepartment of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA.
Gina M DeNicolaDepartment of Metabolism and Physiology, H. Lee. Moffitt Cancer Center, Tampa, FL.
Isaac S HarrisDepartment of Biomedical Genetics, Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY.
David SeptDepartment of Biomedical Engineering, University of Michigan, Ann Arbor, MI.
Frank M MasonDivision of Hematology and Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN.
Jonathan L ColoffDepartment of Physiology and Biophysics, University of Illinois College of Medicine, University of Illinois Cancer Center, Chicago, IL.
University of Illinois Urbana-Champaign · USMassachusetts Institute of Technology · USMoffitt Cancer Center · USUniversity of Michigan · USVanderbilt University Medical Center · USCornell University · USFlorida State University · USUniversity of Rochester Medical Center · US

Funding

Investigation of NRF2-Dependent Metabolic LiabilitiesR37CA230042 · NCI · H. LEE MOFFITT CANCER CTR & RES INST · PI DENICOLA, GINA MARIE · 2018 to 2024
$2.8M
Identifying Proliferation-Independent Metabolic Vulnerabilities in CancerK22CA215828 · NCI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI COLOFF, JONATHAN L. · 2018 to 2020
$564k
NCI NIH HHS K22 CA215828NCI NIH HHS R37 CA230042
6 · The paper itself

Abstract

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 waste product uric acid, which is uniquely abundant in humans relative to traditional

Identifiers

PMID37546939
PMCPMC10402161
OpenAlexW4385332911

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.