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Protein / target

Epidermal growth factor receptor

Encoded byEGFRP00533Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
28
Approved medicines
Open Targets target-level
View by indication →
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Transmembrane receptor protein tyrosine kinase

Primary biology

EGFR/ERBB growth-factor signalling

Strongest disease association

Squamous Cell Carcinoma of Head and Neck

Via encoding gene EGFR · Genetic evidence · score 0.82

Therapeutic position

Established drug target

Small molecules and antibodies

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses.

View complete UniProt function annotation

Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536, PubMed:2790960, PubMed:35538033). Known ligands include EGF, TGFA/TGF-alpha, AREG, epigen/EPGN, BTC/betacellulin, epiregulin/EREG and HBEGF/heparin-binding EGF (PubMed:12297049, PubMed:15611079, PubMed:17909029, PubMed:20837704, PubMed:27153536, PubMed:2790960, PubMed:7679104, PubMed:8144591, PubMed:9419975). Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation on key cytoplasmic residues. The phosphorylated receptor recruits adapter proteins like GRB2 which in turn activates complex downstream signaling cascades. Activates at least 4 major downstream signaling cascades including the RAS-RAF-MEK-ERK, PI3 kinase-AKT, PLCgamma-PKC and STATs modules (PubMed:27153536). May also activate the NF-kappa-B signaling cascade (PubMed:11116146). Also directly phosphorylates other proteins like RGS16, activating its GTPase activity and probably coupling the EGF receptor signaling to the G protein-coupled receptor signaling (PubMed:11602604). Also phosphorylates MUC1 and increases its interaction with SRC and CTNNB1/beta-catenin (PubMed:11483589). Positively regulates cell migration via interaction with CCDC88A/GIV which retains EGFR at the cell membrane following ligand stimulation, promoting EGFR signaling which triggers cell migration (PubMed:20462955). Plays a role in enhancing learning and memory performance (By similarity). Plays a role in mammalian pain signaling (long-lasting hypersensitivity) (By similarity)

Subcellular location

Cell membraneEndoplasmic reticulum membraneGolgi apparatus membraneNucleus membraneEndosomeEndosome membraneNucleusSecreted
Domains and Gene Ontology detail (84)

Domains & features

Protein kinase

Gene Ontology

  • Cbasal plasma membrane
  • Cbasolateral plasma membrane
  • Ccell junction
  • Ccell surface
  • Cclathrin-coated endocytic vesicle membrane
  • Ccytoplasm
  • Cearly endosome membrane
  • Cendoplasmic reticulum membrane
  • Cendosome
  • Cendosome membrane
  • Cextracellular space
  • Cfocal adhesion

1210 aa · 134 kDa · 4 isoforms

Biological roles

Reactome v97

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Receptor tyrosine kinase signallingUniProt · GO · ReactomeCell migrationUniProt · GO · ReactomeGrowth-factor signallingGO · ReactomeCell proliferation & survivalGO · ReactomeOncogenic signallingReactomeCell-cycle regulationGO
View supporting evidence

Receptor tyrosine kinase signalling

  • ·Receptor tyrosine kinase binding ligands of the EGF family and activating several signal…
  • ·transmembrane receptor protein tyrosine kinase activity
  • ·ERBB2-EGFR signaling pathway
  • ·Signaling by ERBB2

Cell migration

  • ·Receptor tyrosine kinase binding ligands of the EGF family and activating several signal…
  • ·positive regulation of cell migration
  • ·ERBB2 Regulates Cell Motility

Growth-factor signalling

  • ·epidermal growth factor binding
  • ·epidermal growth factor receptor activity
  • ·cellular response to epidermal growth factor stimulus
  • ·epidermal growth factor receptor signaling pathway

Cell proliferation & survival

  • ·positive regulation of cell population proliferation
  • ·PIP3 activates AKT signaling
  • ·PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling

Oncogenic signalling

  • ·Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants
  • ·Constitutive Signaling by Aberrant PI3K in Cancer

Cell-cycle regulation

  • ·positive regulation of G1/S transition of mitotic cell cycle
View underlying pathways (25)

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Interaction neighbourhood

STRING v12.0

Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.

PTPN11HBEGFNRG1TGFAERBB2DCNSHC1SOS1PIK3CAERBB3EGFR

10 strongest partners — larger node and heavier line mean higher confidence

Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.

Approved medicines with mapped indications

6 medicines · 3 areas

Approved therapies targeting this protein, grouped by what they are approved to treat — the disease-first view of the medicines below. Relationships come from the canonical approved-indication graph (ChEMBL phase-4), the same source as the drug cards.

Carcinoma, Non-Small-Cell Lung4 medicines
Pancreatic Neoplasms1 medicine

28 medicines meet Open Targets' target-level approved-medicine definition; the 6 shown here are those on this page with a canonical approved disease indication in the graph. Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.

Drugs targeting this protein

10

How approved and investigational drugs engage this protein — mechanism and action type, direct vs complex targeting, and how broadly each acts across other targets. A drug-first view (the section above groups the approved ones disease-first); direct binders with few recorded targets are listed first.

gefitinib
Narrow target profileApprovedInhibitor

Epidermal growth factor receptor erbB1 inhibitor

Indicated for Carcinoma, Non-Small-Cell Lung, Neoplasms

Direct interaction with this protein · Only this protein recorded as a target

osimertinib
Narrow target profileApprovedInhibitor

Epidermal growth factor receptor erbB1 inhibitor

Indicated for Neoplasms

Direct interaction with this protein · Only this protein recorded as a target

amivantamab
Narrow target profileApprovedInhibitor

Epidermal growth factor receptor erbB1 inhibitor

Indicated for Carcinoma, Non-Small-Cell Lung, Neoplasms

Direct interaction with this protein · 1 of 2 recorded protein targets — narrow recorded profile

nimotuzumab
Narrow target profileApprovedInhibitor

Epidermal growth factor receptor erbB1 inhibitor

Direct interaction with this protein · Only this protein recorded as a target

Erlotinib Hydrochloride
Narrow target profileApprovedInhibitor

Epidermal growth factor receptor erbB1 inhibitor

Indicated for Carcinoma, Non-Small-Cell Lung, Pancreatic Neoplasms

Direct interaction with this protein · Only this protein recorded as a target

pyrotinib
Narrow target profilePhase 3Inhibitor

Epidermal growth factor receptor erbB1 inhibitor

Direct interaction with this protein · 1 of 2 recorded protein targets — narrow recorded profile

View all 10 targeting drugs
mobocertinib
Narrow target profileApprovedInhibitor

Epidermal growth factor receptor erbB1 inhibitor

Indicated for Neoplasms

Direct interaction with this protein · Only this protein recorded as a target

neratinib
Narrow target profileApprovedInhibitor

Epidermal growth factor receptor erbB1 inhibitor

Direct interaction with this protein · 1 of 3 recorded protein targets — narrow recorded profile

brigatinib
Narrow target profileApprovedInhibitor

Epidermal growth factor receptor erbB1 inhibitor

Indicated for Carcinoma, Non-Small-Cell Lung, Neoplasms

Direct interaction with this protein · 1 of 2 recorded protein targets — narrow recorded profile

lazertinib
Narrow target profileApprovedInhibitor

Epidermal growth factor receptor erbB1 inhibitor

Direct interaction with this protein · Only this protein recorded as a target

ChEMBL mechanism, action type, target identity and approved indications. Open Targets clinical status.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene EGFR

Gene-level evidence surfaced through the gene EGFRthat encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Carcinoma, Non-Small-Cell Lung
0.98Well supported

Clinical evidence dominant · Open Targets 0.85

Squamous Cell Carcinoma of Head and Neck
0.97Well supported

Genetic evidence dominant · Open Targets 0.73

Adenocarcinoma of Lung
0.96Well supported

Genetic evidence dominant · Open Targets 0.77

Lung Neoplasms
0.96Well supported

Genetic evidence dominant · Open Targets 0.72

Neoplasms
0.90Well supported

Clinical evidence dominant · Open Targets 0.74

View evidence synthesis (5)
Carcinoma, Non-Small-Cell LungWell supported
0.98
agreement 0.901.00
Clinical30%Genetic30%Somatic mutation22%Pathway13%Literature6%Genetic literaturedup

Open Targets aggregate 0.85 · 5 independent evidence families · 1 not counted as duplicate

Squamous Cell Carcinoma of Head and NeckWell supported
0.97
agreement 0.881.00
Genetic38%Clinical30%Somatic mutation14%Pathway11%Literature7%

Open Targets aggregate 0.73 · 5 independent evidence families

Adenocarcinoma of LungWell supported
0.96
agreement 0.881.00
Genetic32%Somatic mutation25%Clinical22%Pathway15%Literature7%

Open Targets aggregate 0.77 · 5 independent evidence families

Lung NeoplasmsWell supported
0.96
agreement 0.871.00
Genetic39%Clinical31%Somatic mutation22%Literature7%Genetic literaturedup

Open Targets aggregate 0.72 · 4 independent evidence families · 1 not counted as duplicate

NeoplasmsWell supported
0.90
agreement 0.811.00
Clinical46%Pathway25%Genetic20%Literature10%

Open Targets aggregate 0.74 · 4 independent evidence families

The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations
Carcinoma, Non-Small-Cell Lung0.85
Adenocarcinoma of Lung0.77
Neoplasms0.74
Squamous Cell Carcinoma of Head and Neck0.73
Lung Neoplasms0.72
Breast Neoplasms0.68
Colorectal adenocarcinoma0.68
Glioblastoma0.65
Inflammatory skin and bowel disease, neonatal, 20.64

Drug development

82 compounds recorded · 28 approved · 53 in clinical development · 1 earlier-stage

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 10 drugs that target this protein in Forefront's canonical graph (6 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (10)
RUSERONTINIBPhase 3
TESEVATINIBPhase 3
AFATINIBApproval
CETUXIMAB SAROTALOCANApproval
MDX-447Phase 1
ALLITINIBPhase 1
BRIGATINIBApproval
LAZERTINIBApproval
IMGATUZUMABPhase 2
AFATINIB DIMALEATEApproval

Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.

Tractability

Small moleculesStrong

Approved Drug and Structure with Ligand support this modality.

AntibodiesStrong

Approved Drug and UniProt loc high conf support this modality.

Protein degradersEmerging

Feasibility evidence (literature and uniprot ubiquitination) — no clinical-stage drug of this modality recorded.

Other modalitiesStrong

Advanced Clinical support this modality.

View underlying tractability evidence (17)
SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · High-Quality PocketSM · Druggable FamilyAB · Approved DrugAB · UniProt loc high confAB · GO CC high confAB · UniProt loc med confAB · UniProt SigP or TMHMMAB · Human Protein Atlas locPR · LiteraturePR · UniProt UbiquitinationPR · Database UbiquitinationPR · Half-life DataPR · Small Molecule BinderOC · Advanced Clinical

Raw Open Targets tractability assessment buckets, by modality.

Safety-related annotations

alopeciaBrennan et al. (2024)ocular keratitisBrennan et al. (2024)HepatotoxicityBrennan et al. (2024)Skin rashBrennan et al. (2024)diarrhoeaBrennan et al. (2024)DiarrheaClinPGxAST increaseBrennan et al. (2024)regulation of catalytic activityToxCastepithelial inflammationBrennan et al. (2024)drug toxicityClinPGxdecreased appetiteBrennan et al. (2024)rashClinPGx

Terms indexed against this target in Open Targets' safety data, with their datasource. These are annotations, not causal claims: the direction of effect (whether activation or inhibition is implicated), species and evidence strength are not captured here, so an entry does not mean that modulating this target is known to cause that condition.

Clinical trials

30

Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.

View all trials (26)

NOT_YET_RECRUITING · via osimertinib · NCT06323148

RECRUITING · via nimotuzumab · NCT04821843

ClinicalTrials.gov via the drug-target graph.

What's happening now

12

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for 9 drugs that target this protein, plus publications where such a drug is a genuine subject. Every item is reached indirectly through the drug, not the protein itself; incidental mentions (a paper that merely measures a drug) and press items are excluded.

  1. Trial status changed2026-07-22

    Phase I Study of the Pan-ERBB Inhibitor Neratinib Given in Combination With Everolimus, Palbociclib, or Trametinib in Advanced Cancer Subjects With EGFR Mutation/Amplification, HER2 Mutation/Amplification, or HER3/4 Mutation or KRAS Mutation

    Status changed to Terminated · ClinicalTrials.gov · via neratinib

  2. Regulatory approval2025-01-20

    Approval: Lazcluze (EMA)

    ema · regulatory · ema · via lazertinib

  3. Withdrawn from market2024-09-27

    Market withdrawal: Gefitinib Mylan (EMA)

    ema · market · ema · via gefitinib

  4. New publication2024-06-26
    Amivantamab plus Lazertinib in Previously Untreated <i>EGFR</i>-Mutated Advanced NSCLC.

    The New England journal of medicine · 2024 · 303 citations · Europe PMC · via amivantamab

  5. New publication2023-10-31
    Pyrotinib versus placebo in combination with trastuzumab and docetaxel as first line treatment in patients with HER2 positive metastatic breast cancer (PHILA): randomised, double blind, multicentre, phase 3 trial.

    BMJ (Clinical research ed.) · 2023 · 79 citations · Europe PMC · via pyrotinib

  6. New publication2023-08-30
    Nimotuzumab Plus Gemcitabine for K-Ras Wild-Type Locally Advanced or Metastatic Pancreatic Cancer.

    Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2023 · 37 citations · Europe PMC · via nimotuzumab

  7. New publication2023-06-01
    Current treatment strategies for EGFR-mutated non-small cell lung cancer: from first line to beyond osimertinib resistance.

    Japanese journal of clinical oncology · 2023 · 59 citations · Europe PMC · via osimertinib

  8. New publication2023-01-31
    Adjuvant Osimertinib for Resected EGFR-Mutated Stage IB-IIIA Non-Small-Cell Lung Cancer: Updated Results From the Phase III Randomized ADAURA Trial.

    Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2023 · 308 citations · Europe PMC · via osimertinib

  9. New publication2022-12-08
    Therapeutic strategies for EGFR-mutated non-small cell lung cancer patients with osimertinib resistance.

    Journal of hematology & oncology · 2022 · 271 citations · Europe PMC · via osimertinib

  10. New publication2021-12-16
    Treatment Outcomes and Safety of Mobocertinib in Platinum-Pretreated Patients With EGFR Exon 20 Insertion-Positive Metastatic Non-Small Cell Lung Cancer: A Phase 1/2 Open-label Nonrandomized Clinical Trial.

    JAMA oncology · 2021 · 233 citations · Europe PMC · via mobocertinib

  11. Regulatory approval2021-12-09

    Approval: Rybrevant (EMA)

    ema · regulatory · ema · via amivantamab

  12. Regulatory approval2018-11-22

    Approval: Alunbrig (EMA)

    ema · regulatory · ema · via brigatinib

Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.

Related family literature

51

Papers about “ErbB Receptors” — a broader family this protein belongs to. Shown as context; not counted as papers specifically about this protein.

NSCLC: from tumorigenesis, immune checkpoint misuse to current and future targeted therapy.

Raskova Kafkova L · Frontiers in immunology · 2024

via ErbB Receptors

Amivantamab plus Lazertinib in Previously Untreated <i>EGFR</i>-Mutated Advanced NSCLC.

Cho BC · The New England journal of medicine · 2024

via ErbB Receptors

Europe PMC literature, reached through curated HGNC family membership. Membership is a taxonomic relationship — it does not imply this protein participates in every mechanism these papers discuss.