# EGFR C797S

Source: https://onco.cc/terms/c797s/  
OnCo record `c797s` (Term). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

A mutation that stops osimertinib from binding to EGFR; the main on-target way lung cancers escape it.

## Summary

EGFR C797S is a mutation at the covalent binding site that stops osimertinib from attaching to EGFR, and it is the main on-target route by which lung cancers escape the drug. It arises in a minority of patients progressing on osimertinib, either in cis or in trans with T790M, and it can be detected in circulating tumour DNA by liquid biopsy. No fourth-generation EGFR inhibitor is yet approved, with BLU-945 and others discontinued or still early, so amivantamab-based and antibody-drug conjugate regimens are the practical answer. The first-line pairing of amivantamab and lazertinib is designed partly to pre-empt this escape route. The term belongs to the wider topic of acquired resistance and appears in the resistance-routes map and the drug-tolerant persister pathway.

## Fields

- Kind: Term
- Last checked: 2026-09-06

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Osimertinib
- Thress et al., Acquired EGFR C797S mutation mediates resistance to AZD9291 (Nature Medicine 2015): https://doi.org/10.1038/nm.3854

## Connected records

- cancers: [EGFR-mutated non-small-cell lung cancer](https://onco.cc/cancers/egfr-mutant-nsclc/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/)
- technologies: [Liquid biopsy (ctDNA)](https://onco.cc/technologies/liquid-biopsy/)
- targets: [EGFR](https://onco.cc/targets/egfr/)
- terms: [Drug resistance (primary and acquired)](https://onco.cc/terms/resistance/)
- key papers: [Acquired EGFR C797S mutation mediates resistance to AZD9291 in non-small cell lung cancer harboring EGFR T790M](https://onco.cc/key-papers/paper-thress-nat-med/)
- pairings: [Amivantamab + lazertinib (first-line EGFR NSCLC)](https://onco.cc/pairings/amivantamab-plus-lazertinib/)
- bottlenecks: [Acquired resistance to every therapy](https://onco.cc/bottlenecks/b-resistance/)
- pathways: [Drug-tolerant persister cells](https://onco.cc/pathways/drug-tolerant-persisters/), [Receptor tyrosine kinase activation](https://onco.cc/pathways/rtk-activation/), [Resistance routes: how a blocked pathway comes back](https://onco.cc/pathways/resistance-routes-map/)
- biomarkers: [EGFR T790M](https://onco.cc/biomarkers/egfr-t790m/)

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