Evidence map›Paper›PMID 40200028›Full record

ArticleScientific reports2025

Subclonal response heterogeneity to define cancer organoid therapeutic sensitivity.

Jeremy D Kratz, Shujah Rehman, Katherine A Johnson, Amani A Gillette, Aishwarya Sunil, Peter F Favreau, Cheri A Pasch, Devon Miller, Lucas C Zarling, Austin H Yeung and 24 more

Abstract read
In one paragraph

Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing 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

14 citing papers in PubMed.

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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

34 authors.

Jeremy D KratzDivision of Hematology, Medical Oncology and Palliative Care, Department of Medicine, School of Medicine and Public Health, University of Wisconsin, University of Wisconsin, Madison, WI, USA.
Shujah RehmanMorgridge Institute for Research, Madison, WI, USA.
Katherine A JohnsonMcArdle Laboratory for Cancer Research, Department of Oncology, University of Wisconsin, Madison, WI, USA.
Amani A GilletteMorgridge Institute for Research, Madison, WI, USA.
Aishwarya SunilDivision of Hematology, Medical Oncology and Palliative Care, Department of Medicine, School of Medicine and Public Health, University of Wisconsin, University of Wisconsin, Madison, WI, USA.
Peter F FavreauMorgridge Institute for Research, Madison, WI, USA.
Cheri A PaschUniversity of Wisconsin Carbone Cancer Center, Madison, WI, USA.
Devon MillerUniversity of Wisconsin Carbone Cancer Center, Madison, WI, USA.
Lucas C ZarlingUniversity of Wisconsin Carbone Cancer Center, Madison, WI, USA.
Austin H YeungUniversity of Wisconsin Carbone Cancer Center, Madison, WI, USA.
Linda ClipsonMcArdle Laboratory for Cancer Research, Department of Oncology, University of Wisconsin, Madison, WI, USA.
Samantha J AndersonUniversity of Wisconsin Carbone Cancer Center, Madison, WI, USA.
Alyssa K SteimleUniversity of Wisconsin Carbone Cancer Center, Madison, WI, USA.
Carley M SpracklingUniversity of Wisconsin Carbone Cancer Center, Madison, WI, USA.
Kayla K LemmonUniversity of Wisconsin Carbone Cancer Center, Madison, WI, USA.
Daniel E AbbottUniversity of Wisconsin Carbone Cancer Center, Madison, WI, USA.
Mark E BurkardDivision of Hematology, Medical Oncology and Palliative Care, Department of Medicine, School of Medicine and Public Health, University of Wisconsin, University of Wisconsin, Madison, WI, USA.
Michael F BassettiUniversity of Wisconsin Carbone Cancer Center, Madison, WI, USA.
Jens C EickhoffUniversity of Wisconsin Carbone Cancer Center, Madison, WI, USA.
Eugene F FoleyUniversity of Wisconsin Carbone Cancer Center, Madison, WI, USA.
Charles P HeiseUniversity of Wisconsin Carbone Cancer Center, Madison, WI, USA.
Randall J KimpleUniversity of Wisconsin Carbone Cancer Center, Madison, WI, USA.
Elise H LawsonUniversity of Wisconsin Carbone Cancer Center, Madison, WI, USA.
Noelle K LoConteDivision of Hematology, Medical Oncology and Palliative Care, Department of Medicine, School of Medicine and Public Health, University of Wisconsin, University of Wisconsin, Madison, WI, USA.
Sam J LubnerDivision of Hematology, Medical Oncology and Palliative Care, Department of Medicine, School of Medicine and Public Health, University of Wisconsin, University of Wisconsin, Madison, WI, USA.
Daniel L MulkerinDivision of Hematology, Medical Oncology and Palliative Care, Department of Medicine, School of Medicine and Public Health, University of Wisconsin, University of Wisconsin, Madison, WI, USA.
Kristina A MatkowskyjUniversity of Wisconsin Carbone Cancer Center, Madison, WI, USA.
Cristina B SangerUniversity of Wisconsin Carbone Cancer Center, Madison, WI, USA.
Nataliya V UbohaDivision of Hematology, Medical Oncology and Palliative Care, Department of Medicine, School of Medicine and Public Health, University of Wisconsin, University of Wisconsin, Madison, WI, USA.
Sean J McilwainDepartment of Biostatistics and Medical Informatics, University of Wisconsin, Madison, WI, USA.
Irene M OngDepartment of Biostatistics and Medical Informatics, University of Wisconsin, Madison, WI, USA.
Evie H CarchmanUniversity of Wisconsin Carbone Cancer Center, Madison, WI, USA.
Melissa C SkalaUniversity of Wisconsin Carbone Cancer Center, Madison, WI, USA.
Dustin A DemingDivision of Hematology, Medical Oncology and Palliative Care, Department of Medicine, School of Medicine and Public Health, University of Wisconsin, University of Wisconsin, Madison, WI, USA. ddeming@medicine.wisc.edu.

Funding

Project 3: Modulation of the head and neck tumor immune microenvironment by targeting the TAM family of receptorsP50CA278595 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI Jenny E. Gumperz · 2022 to 2026
$12.5M
Training in Cancer Biology Training GrantT32CA009135 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI SUGDEN, WILLIAM M. · 1985 to 2024
$10.4M
The Center for Label-free Imagingand Multiscale Biophotonics (CLIMB)P41EB031772 · NIBIB · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI Stephen A Boppart · 2022 to 2026
$7.6M
Optical imaging to predict cell-level genetic heterogeneity and treatment sensitivity in colorectal cancerR37CA226526 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI DEMING, DUSTIN A · 2018 to 2024
$4.2M
Functional optical imaging for rapid, label-free predictions of treatment response and clonal evolution in patient-derived cancer organoidsR01CA272855 · NCI · MORGRIDGE INSTITUTE FOR RESEARCH, INC. · PI Dustin A Deming, Melissa Caroline Skala · 2023 to 2026
$3.1M
BLRD VA IK2 BX006146NCI NIH HHS P50 CA278595NCI NIH HHS R01 CA272855NCI NIH HHS R37 CA226526NCI NIH HHS T32 CA009135NIBIB NIH HHS P41 EB031772
6 · The paper itself

Abstract

Tumor heterogeneity is predicted to confer inferior clinical outcomes with precision-based strategies, however, modeling heterogeneity in a manner that still represents the tumor of origin remains a formidable challenge. Sequencing technologies are limited in their ability to identify rare subclonal populations and predict response to treatments for patients. Patient-derived organotypic cultures have significantly improved the modeling of cancer biology by faithfully representing the molecular features of primary malignant tissues. Patient-derived cancer organoid (PCO) cultures contain subclonal populations with the potential to recapitulate heterogeneity, although treatment response assessments commonly ignore diversity in the molecular profile or treatment response. Here, we demonstrate the advantage of evaluating individual PCO heterogeneity to enhance the sensitivity of these assays for predicting clinical response. Additionally, organoid subcultures identify subclonal populations with altered treatment response. Finally, dose escalation studies of PCOs to targeted anti-EGFR therapy are utilized which reveal divergent pathway expression when compared to pretreatment cultures. Overall, these studies demonstrate the importance of population-based organoid response assessments, the use of PCOs to identify molecular heterogeneity not observed with bulk tumor sequencing, and PCO heterogeneity for understanding therapeutic resistance mechanisms.

Indexed as

Antineoplastic AgentsNeoplasmsOrganoidsErbB ReceptorsGenetic HeterogeneityHumansAntineoplastic AgentsErbB ReceptorsClonal heterogeneityColorectal cancerEGFROrganoidsTargeted therapy

Identifiers

PMID40200028
PMCPMC11978853

What OpenQuestion holds

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Registered trials

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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.