# Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors

Source: https://onco.cc/key-papers/paper-sequist-sci-transl-med/  
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## TL;DR

Paper cited by two term pages, indexed on Europe PMC as PubMed record 21430269 and published in Science Translational Medicine; the citing pages link this DOI, which is how the record was matched.

## Summary

Lung cancers harboring mutations in the epidermal growth factor receptor (EGFR) respond to EGFR tyrosine kinase inhibitors, but drug resistance invariably emerges. To elucidate mechanisms of acquired drug resistance, we performed systematic genetic and histological analyses of tumor biopsies from 37 patients with drug-resistant non-small cell lung cancers (NSCLCs) carrying EGFR mutations. All drug-resistant tumors retained their original activating EGFR mutations, and some acquired known mechanisms of resistance including the EGFR T790M mutation or MET gene amplification. Some resistant cancers showed unexpected genetic changes including EGFR amplification and mutations in the PIK3CA gene, whereas others underwent a pronounced epithelial-to-mesenchymal transition. Surprisingly, five resistant tumors (14%) transformed from NSCLC into small cell lung cancer (SCLC) and were sensitive to standard SCLC treatments. In three patients, serial biopsies revealed that genetic mechanisms of resistance were lost in the absence of the continued selective pressure of EGFR inhibitor treatment, and such cancers were sensitive to a second round of treatment with EGFR inhibitors. Collectively, these results deepen our understanding of resistance to EGFR inhibitors and underscore the importance of repeatedly assessing cancers throughout the course of the disease.

Indexed on Europe PMC as PubMed record 21430269 (DOI 10.1126/scitranslmed.3002003). Matched by DOI alone: two term pages cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.

## Fields

- Kind: Key paper
- Last checked: 2026-09-22
- Tags: europepmc-ingest
- Journal: Science Translational Medicine
- Year: 2011
- DOI: 10.1126/scitranslmed.3002003
- Authors: Sequist LV, Waltman BA, Dias-Santagata D, et al.
- What it means: Two term pages on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.
- Caveats: Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper.

## Sources

- Sci Transl Med 2011: https://doi.org/10.1126/scitranslmed.3002003
- PubMed: https://pubmed.ncbi.nlm.nih.gov/21430269/
- Europe PMC: https://europepmc.org/article/MED/21430269

## Connected records

- terms: [Histologic transformation](https://onco.cc/terms/histologic-transformation/), [MET amplification (bypass resistance)](https://onco.cc/terms/met-amplification/)
- journals: [Science Translational Medicine](https://onco.cc/journals/science-translational-medicine/)

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