Evidence map›Paper›PMID 40930104›Full record

ArticleCell genomics2025

Detection of heterogeneous resistance mechanisms to tyrosine kinase inhibitors from cell-free DNA.

Heather A Parsons, Conor Messer, Katheryn Santos, Jakob Weiss, David Merrell, Brian P Danysh, Melissa E Hughes, Gregory J Kirkner, Ashka Patel, Julian Hess and 17 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell genomics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Liquid biopsy in solid tumours: expert opinion paper of the European society of pathology.Virchows Archiv : an international journal of pathology · 2026
    Review
  2. 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

27 authors.

Heather A ParsonsMedical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA. Electronic address: hparsons@fredhutch.org.
Conor MesserBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Katheryn SantosMedical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, MA, USA.
Jakob WeissBroad Institute of MIT and Harvard, Cambridge, MA, USA.
David MerrellBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Brian P DanyshBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Melissa E HughesMedical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Yale Cancer Center, New Haven, CT, USA.
Gregory J KirknerMedical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Ashka PatelMedical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Julian HessBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Kerry SendrickMedical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Chip StewartBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Elizabeth GrantMedical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Kristy Schlueter-KuckBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Albert GrinshpunMedical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Nikhil WagleMedical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Jamunarani VeeraraghavanBaylor College of Medicine, Houston, TX, USA.
Jose Pablo LeoneMedical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
Rachel A FreedmanMedical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
Otto MetzgerMedical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
Rachel SchiffBaylor College of Medicine, Houston, TX, USA.
Eric P WinerYale Cancer Center, New Haven, CT, USA.
Sara M TolaneyMedical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
Mothaffar RimawiBaylor College of Medicine, Houston, TX, USA.
Ian E KropYale Cancer Center, New Haven, CT, USA.
Gad GetzBroad Institute of MIT and Harvard, Cambridge, MA, USA; Massachusetts General Hospital, Boston, MA, USA.
Nancy U LinMedical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.

Funding

Tissue and Pathology CoreP50CA168504 · NCI · DANA-FARBER CANCER INST · PI MYLES A BROWN · 2013 to 2026
$30.1M
NCI NIH HHS P50 CA168504
6 · The paper itself

Abstract

Though there has been substantial progress in the development of anti-human epidermal growth factor receptor 2 (HER2) therapies to treat HER2-positive metastatic breast cancer (MBC) within the past two decades, most patients still experience disease progression and cancer-related death. HER2-directed tyrosine kinase inhibitors can be highly effective therapies for patients with HER2-positive MBC; however, an understanding of resistance mechanisms is needed to better inform treatment approaches. We performed whole-exome sequencing on 111 patients with 73 tumor biopsies and 120 cell-free DNA samples to assess mechanisms of resistance. In 11 of 26 patients with acquired resistance, we identified alterations in previously characterized genes, such as PIK3CA and ERBB2, that could explain treatment resistance. Mutations in growing subclones identified potential mechanisms of resistance in 5 of 26 patients and included alterations in ESR1, FGFR2, and FGFR4. Additional studies are needed to assess the functional role and clinical utility of these alterations in driving resistance.

Indexed as

Breast NeoplasmsCell-Free Nucleic AcidsDrug Resistance, NeoplasmProtein Kinase InhibitorsClass I Phosphatidylinositol 3-KinasesErb-b2 Receptor Tyrosine KinasesEstrogen Receptor alphaExome SequencingFemaleHumansMiddle AgedMutationReceptor, Fibroblast Growth Factor, Type 2Tyrosine Kinase InhibitorsCell-Free Nucleic AcidsClass I Phosphatidylinositol 3-KinasesERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesESR1 protein, humanEstrogen Receptor alphaFGFR2 protein, humanPIK3CA protein, humanProtein Kinase InhibitorsReceptor, Fibroblast Growth Factor, Type 2Tyrosine Kinase Inhibitorscell-free DNAHER2metastatic breast cancerresistancetyrosine kinase inhibitors

Identifiers

PMID40930104
PMCPMC12802574

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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.