EGFR
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.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · A growth receptor that is mutated in some lung cancers and overproduced in others; the first great success of targeted pills.
- 1 · What it is
A growth receptor that is mutated in some lung cancers and overproduced in others; the first great success of targeted pills.
- 2 · What goes wrong in cancer
EGFR is a receptor tyrosine kinase activating RAS-MAPK and PI3K-AKT. Exon 20 insertions need dedicated drugs.
- 3 · How drugs use it
22 products aim at EGFR: antibodies, antibody-drug conjugates, bispecific antibodies, vaccines and small molecules. Kinases are switched on by binding ATP inside the cell, so most drugs are small molecules shaped to plug that ATP pocket.
Biology
EGFR is a receptor tyrosine kinase activating RAS-MAPK and PI3K-AKT. Exon 20 insertions need dedicated drugs.
- NSCLC (mutations)
- Colorectal (wild-type, antibody target)
- Head and neck squamous
- Glioblastoma (amplification, EGFRvIII)
How common it is, by cancer
| 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 | 10-15% | Activating mutation (US/Europe) | 40-50% in East Asian adenocarcinoma | cBioPortal (TCGA) |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
Afatinib (Gilotrif) is an irreversible EGFR pill for lung cancer, notable for activity against uncommon EGFR mutations (G719X, L861Q, S768I).
A two-armed antibody that blocks EGFR and its escape partner MET, now first-line for EGFR-mutant lung cancer with lazertinib.
An antibody that blocks the EGFR growth receptor. It works in bowel cancers with a normal RAS gene, especially left-sided ones, and is a key partner in the BRAF combination.
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.
A second-generation EGFR pill that beat gefitinib on survival in EGFR-mutant lung cancer but was quickly overshadowed by osimertinib.
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.
The lung-cancer pill whose dramatic responses in a few patients led to the discovery of EGFR mutations in 2004.
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.
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.
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.
A pill taken for a year after trastuzumab to further reduce recurrence in HER2-positive, hormone-positive breast cancer, limited by severe diarrhoea.
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.
Pyrotinib is China's HER2 pill, widely used there with capecitabine and as a comparator for the new Chinese HER2 ADCs.
A vaccine against a glioblastoma-specific mutant protein that looked promising for years and then failed its phase 3 trial in 2016. It is a landmark failure.
An oral drug for EGFR exon 20 insertion lung cancer that succeeded where mobocertinib failed; approved in China (2023) and the US (2025).
AstraZeneca's EGFR×c-MET bispecific ADC, the most advanced in the most crowded next-generation ADC target pair.
Vandetanib was the first drug approved for medullary thyroid cancer (2011), now largely replaced by RET-selective selpercatinib.
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.
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.
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 barely works in bowel cancer. Responses are still modest and short-lived compared with EGFR or ALK inhibitors in lung cancer.
Every resected non-squamous lung cancer should be tested for EGFR mutations, because patients who carry one live longer if they take osimertinib for three years after surgery. The trial does not tell us whether adjuvant chemotherapy can be omitted, nor what happens on relapse after osimertinib, and the three-year duration was chosen empirically.
Patients with head and neck squamous cell cancer that has recurred or spread should be treated first with pembrolizumab: alone if their tumour is strongly PD-L1 positive and they can wait for a slower response, or with chemotherapy if the tumour is bulky or PD-L1 low. Cetuximab-based chemotherapy is no longer the default. Long-term follow-up shows a small but real group of patients alive at four to five years, which was almost unheard of before.
Anyone diagnosed with advanced lung cancer should have EGFR testing before treatment, because osimertinib as the first drug gives the longest disease control, protects the brain, and is well tolerated. Chemotherapy is not the first step for these patients. The remaining questions are whether to intensify upfront (adding chemotherapy or amivantamab) and how to treat resistance when it develops.
Latest papers
topQuery 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.
Pages like this
not linked directly; found by shared links- TargetALK
Shares Aichi Cancer Center, On-target resistance mutations (gatekeeper, solvent-front, compound), Myung-Ju Ahn, LUNGevity Foundation (and GO2 for Lung Cancer) and the tags driver, kinase.
- TargetBRAF
Shares Sidedness (left vs right colon), René Bernards, Ryan B. Corcoran, Downstream and upstream and the tags driver, kinase.
- TargetPIK3CA / PI3K-alpha
Shares Vanderbilt-Ingram Cancer Center, Oncogene, Hallmark: sustaining proliferative signalling, Resistance routes: how a blocked pathway comes back and the tags driver, kinase.
- TargetROS1
Shares On-target resistance mutations (gatekeeper, solvent-front, compound), LUNGevity Foundation (and GO2 for Lung Cancer), Sequence: targeted therapy before immunotherapy in driver-positive NSCLC, Receptor tyrosine kinase activation and the tags driver, kinase.
- TargetRET
Shares Vandetanib, Sequence: targeted therapy before immunotherapy in driver-positive NSCLC, Shanghai Chest Hospital, Receptor tyrosine kinase activation and the tags driver, kinase.
- TargetFGFR2
Shares National Cancer Centre Singapore, Receptor tyrosine kinase activation, PI3K / AKT / mTOR, RAS / RAF / MEK / ERK (MAPK) and the tags driver, kinase.
- TargetKIT
Shares Receptor tyrosine kinase activation, PI3K / AKT / mTOR, RAS / RAF / MEK / ERK (MAPK), Small-molecule kinase inhibitors and the tags driver, kinase.
- TargetFLT3
Shares Receptor tyrosine kinase activation, Small-molecule kinase inhibitors and the tags driver, kinase.