Evidence map›Paper›PMID 40938276›Full record

ArticleJournal of biomedical materials research. Part A2025

Targeting Cell-Matrix Induced Chemoresistance With Regorafenib in a 3D Model of Osteosarcoma.

Rameshwar R Rao, Michelle S Huang, Daiyao Zhang, Carla Huerta-López, Christopher Long, Giselle Aviles Rodriguez, Esther A T Mozipo, Sriya Sagi, Sarah C Heilshorn

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of biomedical materials research. Part A, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

9 authors.

Rameshwar R RaoBen Towne Center for Childhood Cancer and Blood Disorders Research, Seattle Children's Research Institute, Seattle, Washington, USA.ORCID 0000-0003-0136-2807
Michelle S HuangDepartment of Chemical Engineering, Stanford University, Stanford, California, USA.ORCID 0000-0002-1814-7786
Daiyao ZhangDepartment of Chemical Engineering, Stanford University, Stanford, California, USA.ORCID 0009-0005-7259-0948
Carla Huerta-LópezDepartment of Materials Science and Engineering, Stanford University, Stanford, California, USA.
Christopher LongDepartment of Materials Science and Engineering, Stanford University, Stanford, California, USA.
Giselle Aviles RodriguezDepartment of Materials Science and Engineering, Stanford University, Stanford, California, USA.
Esther A T MozipoDepartment of Bioengineering, Stanford University, Stanford, California, USA.
Sriya SagiBen Towne Center for Childhood Cancer and Blood Disorders Research, Seattle Children's Research Institute, Seattle, Washington, USA.
Sarah C HeilshornDepartment of Materials Science and Engineering, Stanford University, Stanford, California, USA.ORCID 0000-0002-9801-6304

Funding

Pediatric Scientist Development Program (PSDP) [K12]K12HD000850 · NICHD · YALE UNIVERSITY · PI Sallie R. Permar · 1987 to 2026
$44.1M
Increasing Interest in Hematology Research: Training for Promising StudentsR25DK130827 · NIDDK · STANFORD UNIVERSITY · PI Bonnie L Halpern-Felsher, Kathleen M Sakamoto · 2022 to 2026
$532k
Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNational Science Foundation CBET 2033302National Science Foundation DMR 2103812NICHD NIH HHS K12 HD000850NIDDK NIH HHS R25 DK130827NIH HHS K12-HD000850NIH HHS NIH R25DK130827Stanford Bio-XStanford Cancer InstituteStanford Maternal and Child Health Research Institute
6 · The paper itself

Abstract

Over the past four decades, there has been little advancement in treatment strategies for osteosarcoma (OS), the predominant primary bone tumor in the pediatric patient population. Current therapy involves multiple rounds of chemotherapy and surgical resection, which are associated with significant morbidity and suboptimal survival rates. A key challenge in developing new treatments is the difficulty in replicating the OS tumor microenvironment, particularly cell interactions with the extracellular matrix (ECM). This study uses an in vitro model of OS to investigate the cell response to collagen (COL) type I, the primary component of the OS ECM. After 7 days of culture within three-dimensional COL hydrogels, OS cells displayed a more elongated cellular morphology and reduced sensitivity to the standard chemotherapy used for OS treatment compared to cells grown on two-dimensional substrates. To test whether this model could be used to study treatment strategies used for high-risk OS patients, we applied a metronomic regimen combining regorafenib, a multi-tyrosine kinase inhibitor, with front-line chemotherapy to overcome cell-matrix induced chemoresistance. We identified overexpression of the ATP-binding cassette transporter ABCG2, a drug efflux pump, as a potential mechanism of resistance in 3D culture. Regorafenib's inhibitory effect on ABCG2 suggests a mechanistic basis for its ability to restore chemosensitivity in 3D culture. Altogether, these findings highlight the importance of cell-matrix interactions in in vitro OS models, provide valuable insights into a matrix-induced mechanism of OS chemoresistance, and suggest an approach to its treatment.

Indexed as

Antineoplastic AgentsBone NeoplasmsDrug Resistance, NeoplasmExtracellular MatrixModels, BiologicalOsteosarcomaPhenylurea CompoundsPyridinesATP Binding Cassette Transporter, Subfamily G, Member 2Cell Culture Techniques, Three DimensionalCell Line, TumorHumansAntineoplastic AgentsATP Binding Cassette Transporter, Subfamily G, Member 2Phenylurea CompoundsPyridinesregorafenib3D cancer modelsosteosarcomaregorafenibtyrosine kinase inhibitors

Identifiers

PMID40938276
PMCPMC12614213

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.