Evidence map›Paper›PMID 31078067›Full record

ArticleNeoplasia (New York, N.Y.)2019

Cellular Metabolic Heterogeneity In Vivo Is Recapitulated in Tumor Organoids.

Joe T Sharick, Justin J Jeffery, Mohammad R Karim, Christine M Walsh, Karla Esbona, Rebecca S Cook, Melissa C Skala

Open access · goldAbstract read
In one paragraph

Article in Neoplasia (New York, N.Y.), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed
3.4field-weighted citation impact, top 6% of its field
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

51 citing papers in PubMed, 74 citations in OpenAlex.

  1. Article
  2. Organoids glimpse: the nexus for diverse tumor heterogeneity.Frontiers in cell and developmental biology · 2026
    Review
  3. Article
  4. Review
  5. Article
  6. Resistance to neoadjuvant chemotherapy in breast cancers: a metabolic perspective.Journal of experimental & clinical cancer research : CR · 2025
    Review
  7. Article
  8. Review
  9. Review
  10. Review
  11. Article
  12. Article
  13. Imaging immunometabolismImmunometabolism (Cobham, Surrey) · 2024
    Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Article
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  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 5 institutions in 1 country.

Joe T SharickDepartment of Biomedical Engineering, Vanderbilt University, PMB 351631, 2301 Vanderbilt Place, Nashville, TN, 37235, USA; Morgridge Institute for Research, 330 N. Orchard Street, Madison, WI, 53715, USA.
Justin J JefferyUniversity of Wisconsin Carbone Cancer Center, 600 Highland Avenue, Madison, WI, 53792, USA.
Mohammad R KarimMorgridge Institute for Research, 330 N. Orchard Street, Madison, WI, 53715, USA.
Christine M WalshMorgridge Institute for Research, 330 N. Orchard Street, Madison, WI, 53715, USA.
Karla EsbonaDepartment of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, 3170 UW Medical Foundation Centennial Building, 1685 Highland Avenue, Madison, WI, 53705, USA.
Rebecca S CookDepartment of Biomedical Engineering, Vanderbilt University, PMB 351631, 2301 Vanderbilt Place, Nashville, TN, 37235, USA; Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, PMB 407935 U-3218, Medical Research Building III, Nashville, TN, 37240, USA;; Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN; Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN.
Melissa C SkalaMorgridge Institute for Research, 330 N. Orchard Street, Madison, WI, 53715, USA; Department of Biomedical Engineering, University of Wisconsin-Madison, Engineering Centers Building, 1550 Engineering Drive Room #2130, Madison, WI, 53706. Electronic address: mcskala@wisc.edu.
Morgridge Institute for Research · USUniversity of Wisconsin Carbone Cancer Center · USUniversity of Wisconsin Foundation · USUniversity of Wisconsin–Madison · USVanderbilt University Medical Center · US

Funding

UW COMPREHENSIVE CANCER CENTER SUPPORTP30CA014520 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI AMY TRENTHAM-DIETZ · 1985 to 2026
$142.6M
Harnessing human brain and liver microphysiological systems for testing therapeutics for metastatic melanomaU01TR002383 · NCATS · VANDERBILT UNIVERSITY · PI MURPHY, WILLIAM L., TAYLOR, D. LANSING · 2018 to 2022
$7.6M
Optical imaging of pancreas cancer organoids for drug development and personalized treatmentR01CA211082 · NCI · MORGRIDGE INSTITUTE FOR RESEARCH, INC. · PI SKALA, MELISSA CAROLINE · 2017 to 2021
$3.5M
(PQ7) Quantitative in vivo optical imaging of tumor heterogeneityR01CA205101 · NCI · MORGRIDGE INSTITUTE FOR RESEARCH, INC. · PI SKALA, MELISSA CAROLINE · 2016 to 2020
$1.9M
Cellular-level Optical Metabolic Imaging to Predict Drug Response in CancerR01CA185747 · NCI · VANDERBILT UNIVERSITY · PI SKALA, MELISSA CAROLINE · 2014 to 2019
$1.6M
3D biomimetic image-based stromal models of pancreatic cancer for drug screeningR21CA224280 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI CAMPAGNOLA, PAUL J, SKALA, MELISSA CAROLINE · 2018 to 2019
$373k
NCATS NIH HHS U01 TR002383NCI NIH HHS P30 CA014520NCI NIH HHS R01 CA185747NCI NIH HHS R01 CA205101NCI NIH HHS R01 CA211082NCI NIH HHS R21 CA224280
6 · The paper itself

Abstract

Heterogeneous populations within a tumor have varying metabolic profiles, which can muddle the interpretation of bulk tumor imaging studies of treatment response. Although methods to study tumor metabolism at the cellular level are emerging, these methods provide a single time point "snapshot" of tumor metabolism and require a significant time and animal burden while failing to capture the longitudinal metabolic response of a single tumor to treatment. Here, we investigated a novel method for longitudinal, single-cell tracking of metabolism across heterogeneous tumor cell populations using optical metabolic imaging (OMI), which measures autofluorescence of metabolic coenzymes as a report of metabolic activity. We also investigated whether in vivo cellular metabolic heterogeneity can be accurately captured using tumor-derived three-dimensional organoids in a genetically engineered mouse model of breast cancer. OMI measurements of response to paclitaxel and the phosphatidylinositol-3-kinase inhibitor XL147 in tumors and organoids taken at single cell resolution revealed parallel shifts in metaboltruic heterogeneity. Interestingly, these previously unappreciated heterogeneous metabolic responses in tumors and organoids could not be attributed to tumor cell fate or varying leukocyte content within the microenvironment, suggesting that heightened metabolic heterogeneity upon treatment is largely due to heterogeneous metabolic shifts within tumor cells. Together, these studies show that OMI revealed remarkable heterogeneity in response to treatment, which could provide a novel approach to predict the presence of potentially unresponsive tumor cell subpopulations lurking within a largely responsive bulk tumor population, which might otherwise be overlooked by traditional measurements.

Indexed as

Single-Cell AnalysisAnimalsAntineoplastic AgentsBreast NeoplasmsCell Line, TumorCell ProliferationDisease Models, AnimalFemaleHumansMiceOptical ImagingOrganoidsQuinoxalinesSulfonamidesTumor MicroenvironmentAntineoplastic AgentsQuinoxalinesSulfonamidesXL147

Identifiers

PMID31078067
PMCPMC6514366
OpenAlexW2944159612

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.