Evidence map›Paper›PMID 38605363›Full record

ArticleGenome medicine2024

Single cell lineage tracing reveals clonal dynamics of anti-EGFR therapy resistance in triple negative breast cancer.

Simona Pellecchia, Melania Franchini, Gaetano Viscido, Riccardo Arnese, Gennaro Gambardella

Open access · goldAbstract read
In one paragraph

Article in Genome medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
3.7field-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

16 citing papers in PubMed, 13 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Advances in CRISPR-Cas9 in lineage tracing of model animals.Animal models and experimental medicine · 2025
    Review
  12. Article
  13. Review
  14. Article
  15. Review
  16. Article
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

5 authors at 3 institutions in 1 country.

Simona Pellecchia *Telethon Institute of Genetics and Medicine, Naples, Italy.
Melania Franchini *Telethon Institute of Genetics and Medicine, Naples, Italy.
Gaetano ViscidoTelethon Institute of Genetics and Medicine, Naples, Italy.
Riccardo ArneseTelethon Institute of Genetics and Medicine, Naples, Italy.
Gennaro GambardellaTelethon Institute of Genetics and Medicine, Naples, Italy. gambardella@tigem.it.ORCID 0000-0001-7517-1347
Telethon Institute Of Genetics And Medicine · ITFederico II University Hospital · ITScuola Superiore Meridionale · IT

Funding

My First AIRC grant 23162
6 · The paper itself

Abstract

backgroundMost primary Triple Negative Breast Cancers (TNBCs) show amplification of the Epidermal Growth Factor Receptor (EGFR) gene, leading to increased protein expression. However, unlike other EGFR-driven cancers, targeting this receptor in TNBC yields inconsistent therapeutic responses.

methodsTo elucidate the underlying mechanisms of this variability, we employ cellular barcoding and single-cell transcriptomics to reconstruct the subclonal dynamics of EGFR-amplified TNBC cells in response to afatinib, a tyrosine kinase inhibitor (TKI) that irreversibly inhibits EGFR.

resultsIntegrated lineage tracing analysis revealed a rare pre-existing subpopulation of cells with distinct biological signature, including elevated expression levels of Insulin-Like Growth Factor Binding Protein 2 (IGFBP2). We show that IGFBP2 overexpression is sufficient to render TNBC cells tolerant to afatinib treatment by activating the compensatory insulin-like growth factor I receptor (IGF1-R) signalling pathway. Finally, based on reconstructed mechanisms of resistance, we employ deep learning techniques to predict the afatinib sensitivity of TNBC cells.

conclusionsOur strategy proved effective in reconstructing the complex signalling network driving EGFR-targeted therapy resistance, offering new insights for the development of individualized treatment strategies in TNBC.

Indexed as

Triple Negative Breast NeoplasmsAfatinibCell LineageCell Line, TumorErbB ReceptorsHumansProtein Kinase InhibitorsSignal TransductionAfatinibEGFR protein, humanErbB ReceptorsProtein Kinase Inhibitors

Identifiers

PMID38605363
PMCPMC11008053
OpenAlexW4394711426

What OpenQuestion 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 OpenQuestion graph.