Evidence map›Paper›PMID 42856637›Full record

ArticlebioRxiv : the preprint server for biology2026

Spatially coordinated RTK-ERK signaling dynamics shape osteosarcoma single-cell drug response in the lung microenvironment.

Rawan Makkawi, Carol Halsey, Vaibhav Murthy, Elise C Manalo, Hugo Cros, Xin Yi, Jessie May Cartier, Matthew Chang, Mark Flory, Kelly Guptell and 4 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2026. 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.

No citing paper in PubMed yet.

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

14 authors.

Rawan MakkawiKnight Cancer Institute, Oregon Health and Science University, Portland, Oregon, USA.
Carol HalseyKnight Cancer Institute, Oregon Health and Science University, Portland, Oregon, USA.
Vaibhav MurthyKnight Cancer Institute, Oregon Health and Science University, Portland, Oregon, USA.
Elise C ManaloKnight Cancer Institute, Oregon Health and Science University, Portland, Oregon, USA.
Hugo CrosKnight Cancer Institute, Oregon Health and Science University, Portland, Oregon, USA.
Xin YiKnight Cancer Institute, Oregon Health and Science University, Portland, Oregon, USA.
Jessie May CartierKnight Cancer Institute, Oregon Health and Science University, Portland, Oregon, USA.
Matthew ChangKnight Cancer Institute, Oregon Health and Science University, Portland, Oregon, USA.
Mark FloryKnight Cancer Institute, Oregon Health and Science University, Portland, Oregon, USA.
Kelly GuptellCenter for Childhood Cancers and Blood Diseases, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.
Amy GrossCenter for Childhood Cancers and Blood Diseases, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.
Ryan D RobertsCenter for Childhood Cancers and Blood Diseases, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.
Jeremy CoppermanKnight Cancer Institute, Oregon Health and Science University, Portland, Oregon, USA.
Alexander E DaviesKnight Cancer Institute, Oregon Health and Science University, Portland, Oregon, USA.ORCID 0000-0002-1917-8816

Funding

Understanding the origins of rapid recurrence of pancreatic cancer after resectionP30CA069533 · NCI · OREGON HEALTH & SCIENCE UNIVERSITY · PI Grace B Gill · 1997 to 2026
$60.5M
High Performance Computing and Machine Learning Infrastructure for Oregon Life SciencesS10OD034224 · OD · OREGON HEALTH & SCIENCE UNIVERSITY · PI ELLROTT, KYLE · 2023 to 2023
$2.0M
Direct and indirect MCL1 targeting for high-efficiency therapy of lung metastasis in-vivo and on-a-chipR01CA300732 · NCI · OREGON HEALTH & SCIENCE UNIVERSITY · PI Alexander E Davies · 2026 to 2026
$625k
Targeting ERK-AKT-mediated single-cell drug response heterogeneity in metastatic osteosarcomaK01OD031811 · OD · OREGON HEALTH & SCIENCE UNIVERSITY · PI DAVIES, ALEXANDER E · 2021 to 2025
$599k
NCI NIH HHS P30 CA069533NCI NIH HHS R01 CA300732NIH HHS K01 OD031811NIH HHS S10 OD034224
6 · The paper itself

Abstract

Purpose: Lung metastases are the primary cause of death in osteosarcoma patients and treatment response often vary due to convergence of genetic and phenotypic influences in the context of a dynamic tumor-host tissue environment. The purpose of this study was to determine how dynamic tumor- and host-driven receptor tyrosine kinase (RTK)-ERK signaling interactions contribute to phenotypic drug response heterogeneity. Experimental Design: Live-cell time-lapse microscopy and data-driven dynamical modeling was used to resolve ERK activity, FOSL1/Fra-1 reporter expression, and spatiotemporal cell fate in living, biosensor-expressing osteosarcoma lung metastases Results: MCL1 inhibition induced extensive tumor-cell death; however, persistent ERK Conclusions: Tumor-host and tumor-cell-lysis-induced FGFR-ERK signaling contribute to spatiotemporally heterogeneous adaptive resistance in metastatic osteosarcoma. These data support combinatorial targeting of RTK signaling with cytotoxic or targeted agents as a strategy to block adaptive resistance and improve treatment efficacy.

Identifiers

PMID42856637
PMCPMC13648743

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.