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A growth receptor that is mutated in some lung cancers and overproduced in others; the first great success of targeted pills.
EGFR activating mutations (exon 19 del, L858R) drive ~15% of Western and ~40-50% of East Asian NSCLC; osimertinib is standard first-line. EGFR is also an antibody target in colorectal and head-and-neck cancer (cetuximab, panitumumab) and a component of bispecifics (amivantamab, EGFR×MET; EGFR×HER3 ADCs). Resistance via C797S, MET amplification, and histologic transformation is the central problem.
In plain words · A growth receptor that is mutated in some lung cancers and overproduced in others; the first great success of targeted pills.
Backbone ribbon from PDB 6WVZ. RCSB PDB 6WVZ. The ribbon widens where the chain is folded into a regular pattern and narrows where it is a loose loop.
A growth receptor that is mutated in some lung cancers and overproduced in others; the first great success of targeted pills.
EGFR is a receptor tyrosine kinase activating RAS-MAPK and PI3K-AKT. Exon 20 insertions need dedicated drugs.
51 products aim at EGFR: antibodies, antibody-drug conjugates, bispecific antibodies, vaccines, small molecules and other agents. Kinases are switched on by binding ATP inside the cell, so most drugs are small molecules shaped to plug that ATP pocket.
Would move the TROP2 ADC into the first-line EGFR-mutant setting on top of the standard TKI. Timing is a registry-based estimate. Source
Tumour-specific alteration: 4 of 4 label readouts filed under it measure a sequence variant (EGFR exon 19 deletion, EGFR exon 20 insertion, EGFR L858R, EGFR T790M) absent from normal cells. HPA EGFR: RNA tissue enhanced (placenta 62 nTPM); high antibody staining in 4 normal tissues; highest cancer staining head and neck cancer (4 of 4 high). Distribution: 5 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Lung cancer (all types), Colorectal cancer, Head and neck squamous cell carcinoma, Brain and spinal cord tumours (all types), Biliary tract cancer (all types)); approvals of single-target medicines aimed at it also list Pancreatic ductal adenocarcinoma, Oesophageal cancer, not counted; Open Targets associates it with 17 specific cancer types at or above 0.5 (non-small cell lung carcinoma, lung adenocarcinoma, head and neck squamous cell carcinoma, lung cancer, breast cancer, colorectal adenocarcinoma and more). (Rule 3 of scripts/fetch-target-specificity.ts.)
Sources: EGFR exon 19 deletion label threshold; EGFR exon 20 insertion label threshold; Human Protein Atlas EGFR tissue; Open Targets ENSG00000146648 associations
First described 1984. Earliest sequence paper UniProt cites for the protein: Ullrich et al, Nature, 1984, "Human epidermal growth factor receptor cDNA sequence and aberrant expression of the amplified gene in A431 epidermoid carcinoma cells". Source.
What a pathology or genomic report can say about this target, each with the thresholds approvals use.
Cell lines and mouse models for this target →
EGFR is a receptor tyrosine kinase activating RAS-MAPK and PI3K-AKT. Exon 20 insertions need dedicated drugs.
RNA: tissue enhanced (placenta 62 nTPM), detected in many normal tissues.
Medium: Cervix, Epididymis, Esophagus, Fallopian tube, Gallbladder, Kidney, Liver, Oral mucosa.
RNA cancer enriched: Glioblastoma Multiforme 324 pTPM.
Medium only: breast cancer, ovarian cancer, prostate cancer, thyroid cancer.
HPA EGFR tissue · HPA EGFR pathology · HPA protein class: FDA approved drug targets
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Colorectal cancer | 100% | Wild-type EGFR is the antibody target | Benefit restricted to RAS/BRAF wild-type (~40%) | Wikipedia |
| Head and neck squamous cell carcinoma | 80-90% | Overexpression by IHC | Wikipedia | |
| Glioma & glioblastoma | 40-50% | Amplification | EGFRvIII in ~25-30% | cBioPortal (TCGA) |
| Non-small-cell lung cancer | 12-47% | Activating mutation (any class) | cBioPortal: 143 of 302, 47.4%, in luad_oncosg_2020 (East Asian); 866 of 2,653, 32.6%, in luad_mskcc_2023_met_organotropism; 268 of 915, 29.3%, in lung_msk_2017; 66 of 232, 28.4%, in lung_nci_2022 (never smokers); 662 of 2,621, 25.3%, in nsclc_ctdx_msk_2022; 38 of 110, 34.5%, in luad_cptac_2020; 70 of 566, 12.4%, in luad_tcga_pan_can_atlas_2018; 33 of 230, 14.3%, in luad_tcga_pub. The Lung Cancer Mutation Consortium found sensitising EGFR in 122 of 733, 17%, plus other EGFR mutations in 29 (Kris 2014). | cBioPortal (TCGA) |
| Non-small-cell lung cancer | 13-19% | In-frame deletion around codons 746 to 750 | cBioPortal, samples carrying the class: 382 of 2,653, 14.4%, in luad_mskcc_2023_met_organotropism; 308 of 2,621, 11.8%, in nsclc_ctdx_msk_2022; 117 of 915, 12.8%, in lung_msk_2017; 57 of 302, 18.9%, in luad_oncosg_2020; 38 of 232, 16.4%, in lung_nci_2022; 23 of 566, 4.1%, in luad_tcga_pan_can_atlas_2018. E746_A750del is the single commonest variant (237 of 1,114 EGFR records in luad_mskcc_2023_met_organotropism). | cBioPortal (TCGA) |
| Non-small-cell lung cancer | 9-21% | Exon 21 point mutation | cBioPortal, samples: 289 of 2,653, 10.9%, in luad_mskcc_2023_met_organotropism; 206 of 2,621, 7.9%, in nsclc_ctdx_msk_2022; 82 of 915, 9.0%, in lung_msk_2017; 63 of 302, 20.9%, in luad_oncosg_2020; 20 of 232, 8.6%, in lung_nci_2022; 23 of 566, 4.1%, in luad_tcga_pan_can_atlas_2018. | cBioPortal (TCGA) |
| Non-small-cell lung cancer | 10-15% | Activating mutation (US/Europe) | 40-50% in East Asian adenocarcinoma | cBioPortal (TCGA) |
| Triple-negative breast cancer | 3-6% | Amplification | EGFR amplified (gains included) in 23% of basal-like tumours, alongside PIK3CA 49%, KRAS 32% and BRAF 30% (Cancer Genome Atlas 2012); cBioPortal high-level amplification: 5 of 119, 4.2%, in brca_tcga_pan_can_atlas_2018; 19 of 320, 5.9%, in brca_metabric; 5 of 176, 2.8%, in breast_msk_2018. Growth-factor signalling defines the BL2 subtype (Lehmann 2011). | doi.org |
| Non-small-cell lung cancer | 3-5% | G719X, L861Q, S768I and compound alleles | cBioPortal, samples out of 2,653 in luad_mskcc_2023_met_organotropism: G719X 57 (2.1%), L861Q 30 (1.1%), S768I 30 (1.1%); out of 2,621 in nsclc_ctdx_msk_2022: G719X 28, S768I 19, L861Q 15; out of 915 in lung_msk_2017: G719X 14, L861Q 8, S768I 5. Together they are 117 of 2,653 samples, 4.4%, in the largest cohort. | cBioPortal (TCGA) |
| Gallbladder cancer | 1-3% | Amplification or mutation | Amplification in 8 of 244 samples, 3.3%, and mutation in 3 of 244, 1.2%, in cBioPortal gbc_mskcc_2022; 3.1% of 32 exomes in gbc_shanghai_2014; among the actionable variants in the Chilean cohort (Erices 2025). | cBioPortal (TCGA) |
| Non-small-cell lung cancer | 1-3% | In-frame insertion or duplication in the loop after the C-helix | cBioPortal, samples: 47 of 2,653, 1.8%, in luad_mskcc_2023_met_organotropism; 45 of 2,621, 1.7%, in nsclc_ctdx_msk_2022; 17 of 915, 1.9%, in lung_msk_2017; 4 of 232, 1.7%, in lung_nci_2022; 3 of 302, 1.0%, in luad_oncosg_2020. About 5 to 6% of EGFR-mutant lung adenocarcinoma. | cBioPortal (TCGA) |
| Colorectal cancer | 1-2% | High-level amplification (and acquired ectodomain mutation) | cBioPortal high-level amplification: 101 of 7,237, 1.4%, in crc_msk_2026; 16 of 1,134, 1.4%, in crc_msk_2017; 19 of 1,516 in crc_eo_2020; 4 of 592 in coadread_tcga_pan_can_atlas_2018. Distal tumours are the ones that carry EGFR or HER2 amplification and overexpress epiregulin (Missiaglia 2014). | cBioPortal (TCGA) |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
Afatinib (Gilotrif) is a second-generation pill that binds EGFR, HER2 and HER4 irreversibly, approved in 2013 for EGFR-mutant lung cancer. Its lasting value is activity against the uncommon EGFR mutations G719X, L861Q and S768I, approved in 2018, because osimertinib has displaced it for common mutations and its wild-type EGFR binding causes more rash and diarrhoea.
A two-armed antibody that blocks EGFR and its escape partner MET, now first-line for EGFR-mutant lung cancer with lazertinib.
Aumolertinib is Hansoh's third-generation lung cancer pill, the first China-developed drug of its class, approved for first-line EGFR-mutant lung cancer on the AENEAS trial.
Cetuximab is a chimeric antibody that blocks the EGFR growth receptor. It is used with FOLFIRI or FOLFOX in RAS wild-type, left-sided bowel cancer, with encorafenib in BRAF V600E disease, with KRAS G12C inhibitors, and with radiation or chemotherapy in head and neck cancer; RAS-mutant tumours gain nothing and may be harmed, so RAS testing comes first.
Cetuximab sarotalocan is an EGFR antibody carrying a light-activated dye: after infusion, a red laser is shone on the tumour and the cells burst. It has been approved in Japan since 2020.
The lung cancer gene test that became the first blood-based companion diagnostic the FDA ever approved.
A second-generation EGFR pill that beat gefitinib on survival in EGFR-mutant lung cancer but was quickly overshadowed by osimertinib.
Depatuxizumab mafodotin carried a cell-killing payload to glioblastomas with extra copies of the EGFR gene. It caused serious eye problems and, in the phase 3 INTELLANCE-1 trial, did not help patients live longer, so development stopped in 2019.
E-EDV-D682 is an experimental EDV nanocell (bacterial minicell) drug conjugate from Engeneic Pty in phase 2 trials for pancreatic ductal adenocarcinoma, aimed at EGFR.
Encorafenib is a BRAF inhibitor that, with cetuximab and chemotherapy, became first-line standard for BRAF-mutant colorectal cancer in 2026.
Erlotinib was one of the first EGFR pills for lung cancer; it was approved before anyone knew EGFR mutations predicted who would respond, then redefined by them.
Ficerafusp alfa is an EGFR antibody fused to a TGF-beta sponge, designed to remove the immune-suppressing signal that keeps HPV-negative throat cancers cold.
Furmonertinib is a Chinese lung cancer pill of the same class as osimertinib, which more than doubled the time before cancer grew compared with gefitinib in the FURLONG trial.
The lung-cancer pill whose dramatic responses in a few patients led to the discovery of EGFR mutations in 2004.
A blood test that reads a tumour's mutations without a tissue biopsy and is the FDA-approved gateway to several targeted drugs.
HLX43 is an experimental antibody-drug conjugate from Shanghai Henlius Biotech in phase 3 trials for non-small-cell lung cancer, cervical cancer and ovarian cancer, aimed at PD-L1 and EGFR.
HMBD-001 is an experimental monoclonal antibody from Hummingbird Bioscience in phase 2 trials for non-small-cell lung cancer, head and neck squamous cell carcinoma and oesophageal cancer, aimed at HER3 and EGFR.
HS-20117 is an experimental bispecific antibody from Hansoh BioMedical R&D in phase 3 trials for non-small-cell lung cancer, aimed at EGFR and MET.
Icotinib, approved in 2011, was the first cancer drug invented and developed in China, and it showed that a domestic lung cancer pill could match a Western one head to head.
Izalontamab brengitecan is the first bispecific ADC to succeed in a phase 3 trial, hitting two growth receptors at once in triple-negative breast cancer.
JMT101 is an experimental monoclonal antibody from Shanghai JMT-Bio in phase 3 trials for non-small-cell lung cancer, aimed at EGFR.
JS111 is an experimental small-molecule drug from Suzhou Junjing BioSciences in phase 2 trials for non-small-cell lung cancer, aimed at EGFR and MET.
Lapatinib was the first HER2-blocking pill (2007) and is now mostly a comparator arm and a late-line option, displaced by tucatinib and ADCs.
A third-generation EGFR pill used together with amivantamab as the first regimen to beat osimertinib in EGFR-mutant lung cancer.
Limertinib is Aosaikang's third-generation EGFR inhibitor, approved in China in 2024 for lung cancer with the T790M resistance mutation after earlier EGFR drugs, and in phase 3 trials for first-line use.
MCLA-129 is an experimental bispecific antibody from Betta Pharmaceuticals in phase 2 trials for non-small-cell lung cancer, head and neck squamous cell carcinoma and colorectal cancer, aimed at EGFR and MET.
Mobocertinib was the first oral drug for EGFR exon 20 insertion lung cancer, approved in 2021 and withdrawn in 2023-24 after its confirmatory trial failed.
Necitumumab (Portrazza) is an antibody added to gemcitabine and cisplatin as first treatment for squamous non-small cell lung cancer that has spread; the benefit is modest and it is little used.
A pill taken for a year after trastuzumab to further reduce recurrence in HER2-positive, hormone-positive breast cancer, limited by severe diarrhoea.
Nimotuzumab is a Cuban-developed antibody against EGFR approved in India, China, Cuba and other countries for head and neck cancer, nasopharyngeal cancer and brain tumours, usually with radiotherapy; it causes far less rash than cetuximab but has never been approved in the United States or Europe.
Olmutinib was a Korean-developed EGFR pill approved in South Korea in 2016 for lung cancers that had developed the T790M resistance mutation, the same niche as osimertinib; severe skin reactions and osimertinib's success ended its development.
The first FDA-approved gene panel that could match one biopsy to several different lung cancer drugs at once.
Osimertinib (Tagrisso) is the standard pill for EGFR-mutant lung cancer, now also given after surgery and with chemotherapy or after chemoradiation.
Panitumumab is a fully human EGFR antibody, the preferred first-line partner for chemotherapy in left-sided, RAS-normal bowel cancer after the PARADIGM trial.
A two-armed antibody that blocks EGFR while gripping LGR5, a marker of cancer stem cells, so it hits the cells that regrow tumours.
Poziotinib was a tablet designed to fit the awkward shape of HER2 and EGFR exon 20 mutations in lung cancer. It shrank tumours in some patients but caused severe rash and diarrhoea, and the FDA declined to approve it in 2022.
Pyrotinib is an irreversible pan-ErbB kinase inhibitor pill (EGFR, HER2, HER4) from Jiangsu Hengrui, approved in China since 2018 but not in the US or EU. It is the standard HER2 pill there, given with capecitabine after trastuzumab, and the comparator that new Chinese HER2 ADCs are beating; diarrhoea affects nearly every patient.
Rindopepimut is a peptide vaccine against EGFRvIII, a mutant protein found only on some glioblastomas. After a phase 2 that beat historical controls, the 745-patient double-blind phase 3 ACT IV found no benefit in 2016, and tumours in both arms had lost EGFRvIII at recurrence, a lesson in antigen escape.
Savolitinib is a Chinese-discovered pill that blocks the MET growth signal, approved in China for lung cancers with a MET exon 14 mutation and being tested worldwide with osimertinib.
Silevertinib is an experimental small-molecule drug from Black Diamond Therapeutics in phase 2 trials for non-small-cell lung cancer, aimed at EGFR.
An oral drug for EGFR exon 20 insertion lung cancer that succeeded where mobocertinib failed; approved in China (2023) and the US (2025).
Tempus's tumour-and-normal gene panel, FDA-approved in 2023 as a companion test for EGFR antibodies in bowel cancer.
A family of quick single-gene tests that decide who can have several bowel, lung, breast and bladder cancer drugs.
AstraZeneca's EGFR×c-MET bispecific ADC, the most advanced in the most crowded next-generation ADC target pair.
TQB2922 is an experimental bispecific antibody from Chia Tai Tianqing Pharmaceutical Nanjing Shunxin Pharmaceutical in phase 2 trials for colorectal cancer, aimed at EGFR and MET.
TQB2930 is an experimental bispecific antibody from Chia Tai Tianqing Pharmaceutical in phase 2 trials for HR-positive / HER2-negative breast cancer, aimed at HER2 and EGFR.
TQB6411 is an experimental antibody-drug conjugate from Chia Tai Tianqing Pharmaceutical in phase 2 trials for non-small-cell lung cancer and oesophageal cancer, aimed at EGFR and MET.
Vandetanib was the first drug approved for medullary thyroid cancer (2011), now largely replaced by RET-selective selpercatinib.
A pill that blocked the HER family of growth receptors, tested with capecitabine as second-line treatment for bile duct and gallbladder cancer. It did not beat capecitabine alone in the TreeTopp trial and development stopped.
VRN110755 is an experimental small-molecule drug from Voronoi in phase 2 trials for non-small-cell lung cancer, aimed at EGFR.
Zipalertinib is an experimental small-molecule drug from Taiho Oncology in phase 3 trials for non-small-cell lung cancer, aimed at EGFR.
The 48 most recent of 61 papers; see them all →
The survival benefit first reported in 2023 has held five years after the last dose of adjuvant osimertinib, which answers the worry that a three-year course only delays relapse. Patients with an exon 19 deletion gained most; the L858R estimate crosses one and is less certain. Nothing here changes the recommendation, which already rests on the 2023 analysis, but it tightens the case for testing every resected non-squamous tumour for EGFR mutations.
For a patient weighing the FLAURA2 regimen against osimertinib alone, the extra toxicity is front-loaded: the hardest months are the four induction cycles, and once pemetrexed stops the profile returns to that of osimertinib by itself. Kidney function deserves watching during pemetrexed maintenance.
Patients with newly diagnosed metastatic colorectal cancer whose tumour carries a BRAF V600E mutation, which is about 8-12% of cases, should now be offered encorafenib and cetuximab together with FOLFOX from the start rather than after chemotherapy fails; median survival has roughly doubled to about two and a half years. BRAF testing at diagnosis is therefore essential, alongside RAS and mismatch repair testing. The regimen is more toxic than chemotherapy alone.
Chile has the world's highest gallbladder cancer mortality and until this paper almost no tumour genomics; the lower TP53 rate and high TSC2 and NOTCH1 hint at a different mutational grammar, but the panel and sample size mean the figures need replication.
Patients newly diagnosed with EGFR-mutated advanced lung cancer now have a first-line option that improves survival over osimertinib, particularly if they have high-risk features. The trade-off is intravenous (now subcutaneous) infusions and considerably more skin, nail and clotting toxicity, so osimertinib alone remains reasonable for those who prioritise convenience and tolerability. Both this regimen and osimertinib plus chemotherapy (FLAURA2) are approved; there is no direct comparison.
Stage III lung cancer is now treated by genotype as well as by stage: an EGFR mutation moves a patient from durvalumab consolidation to osimertinib consolidation. It is also the strongest hazard ratio in the lung cancer literature, which is a reason to read the overall survival data carefully when they arrive.
Patients with metastatic colorectal cancer carrying a KRAS G12C mutation (about 3-4% of cases) who have exhausted standard chemotherapy now have a targeted option that works far better than trifluridine-tipiracil or regorafenib. The higher sotorasib dose is clearly superior, and the EGFR antibody is essential because KRAS inhibition alone has little effect in bowel cancer. Responses are still modest and short-lived compared with EGFR or ALK inhibitors in lung cancer.
Adagrasib plus cetuximab is an approved option for previously treated KRAS G12C colorectal cancer, alongside sotorasib plus panitumumab; monotherapy is not enough because EGFR signalling reactivates the pathway.
Query for this target: (TITLE:"EGFR" OR ABSTRACT:"EGFR") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about EGFR, not a curated reading list.
Shares René Bernards, Ryan B. Corcoran, Downstream and upstream, Black Diamond Therapeutics and the tags driver, kinase.
Shares Lemmon and Schlessinger 2010: cell signalling by receptor tyrosine kinases, LUNGevity Foundation (and GO2 for Lung Cancer), Aichi Cancer Center, Shanghai Pulmonary Hospital and the tags driver, kinase.
Shares Imagene AI, Lucence, Vandetanib, Sequence: targeted therapy before immunotherapy in driver-positive NSCLC and the tags driver, kinase.
Shares Comprehensive molecular portraits of human breast tumours, Oncogene, Vanderbilt-Ingram Cancer Center, Hallmark: sustaining proliferative signalling and the tags driver, kinase.
Shares LUNGevity Foundation (and GO2 for Lung Cancer), Sequence: targeted therapy before immunotherapy in driver-positive NSCLC, Clinical implications of plasma-based genotyping with the delivery of personalized therapy in metastatic non-small cell lung cancer, NILE: clinical utility of comprehensive cell-free DNA analysis to identify genomic biomarkers in patients with newly diagnosed metastatic non-small cell lung cancer and the tags driver, kinase.
Shares Black Diamond Therapeutics, National Cancer Centre Singapore, therascreen companion diagnostic kits (KRAS, EGFR, PIK3CA, FGFR, BRAF), KRAS wild-type pancreatic ductal adenocarcinoma and the tags driver, kinase.
Shares Lemmon and Schlessinger 2010: cell signalling by receptor tyrosine kinases, PI3K / AKT / mTOR, Receptor tyrosine kinase activation, RAS / RAF / MEK / ERK (MAPK) and the tags driver, kinase.
Shares Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall, Receptor tyrosine kinase activation, Small-molecule kinase inhibitors and the tags driver, kinase.