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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. This dossier gathers the 51 products (27 approved), 372 trials, 12 pathways and 4 resistance routes in the corpus that involve it, with external identifiers so it can be joined to UniProt, ChEMBL, Open Targets and the rest of biology.
EGFR is a receptor tyrosine kinase activating RAS-MAPK and PI3K-AKT. Exon 20 insertions need dedicated drugs.
| 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.
| Residue | Kind | How common | What it does | Addressed by | Defeats | Source |
|---|---|---|---|---|---|---|
| Exon 19 deletions 746 to 753 | Activating | About 45% of EGFR-mutant NSCLC | In-frame deletions around E746 to A750 in the kinase beta-3/alpha-C loop; the best responders to every generation of TKI. | - | FLAURA, NEJM 2018 | |
| L858R 858 | Activating | About 40% of EGFR-mutant NSCLC | Activation-loop substitution; somewhat shorter PFS than exon 19 deletions on every TKI. | - | FLAURA, NEJM 2018 | |
| G719X / S768I / L861Q 719 | Activating | About 10% of EGFR mutations (uncommon alleles) | Exon 18, 20 and 21 point mutations; afatinib carries a label for them and osimertinib is active. | - | COSMIC: EGFR | |
| Exon 20 insertions 762 to 774 | Activating | About 4 to 10% of EGFR mutations | Insertions after the alpha-C helix that push the drug pocket shut for first- and third-generation TKIs. | Vyse and Huang, Nat Rev Clin Oncol 2019 | ||
| T790M 790 | Resistance | About 50 to 60% of progression on first- and second-generation TKIs | Gatekeeper methionine restores ATP affinity; osimertinib was designed for it. | Yu et al., Clin Cancer Res 2013 | ||
| C797S 797 | Resistance | About 7 to 15% after first-line osimertinib | Loses the cysteine osimertinib bonds to. Fourth-generation allosteric inhibitors are in trials; ADCs against EGFR, HER3 or TROP2 work regardless of genotype. | FLAURA2, NEJM 2023 |
Frequencies are quoted from the source on each row; a blank means no figure was sourced, not that it is rare. Domain boundaries are approximate. Sources for the map: Cancer Hotspots (MSK) · COSMIC: EGFR.
| Modality | Approved | Phase 3 | Phase 2 | Withdrawn or failed |
|---|---|---|---|---|
| Small molecule 15 | ||||
| Antibody 8 | ||||
| Bispecific antibody 6 | - | |||
| Test or device 5 | - | - | - | |
| ADC 3 | - | |||
| Bispecific ADC 2 | - | - | ||
| Small-molecule EGFR exon 20 insertion TKI 2 | - | - | ||
| Small-molecule EGFR TKI 2 | - | - | - | |
| Small-molecule pan-ErbB TKI 2 | - | - | - | |
| Small-molecule third-generation EGFR TKI 2 | - | - | - | |
| EDV nanocell 1 | - | - | - | |
| Small-molecule first-generation EGFR TKI 1 | - | - | - | |
| Small-molecule selective MET TKI 1 | - | - | - | |
| Vaccine or virus 1 | - | - | - |
| Trial | Setting | Result | Products | ||
|---|---|---|---|---|---|
MOUNTAINEER-03 NCT05253651 | 3 | Recruiting | First-line HER2-positive, RAS wild-type metastatic colorectal cancer: tucatinib with trastuzumab and mFOLFOX6 against mFOLFOX6 with bevacizumab or cetuximab | - | |
| 3 | Active | A Phase 3, Open-label, Randomized Study of Lazertinib With Subcutaneous Amivantamab Compared With Intravenous Amivantamab in Patients With EGFR-mutated Advanced or Metastatic Non-small Cell Lung Cancer After Progression on Osimertinib and Chemotherapy | - | ||
| 3 | Active | A Phase III, Randomised, Controlled, Multi-center, 3-Arm Study of Neoadjuvant Osimertinib as Monotherapy or in Combination With Chemotherapy Versus Standard of Care Chemotherapy Alone for the Treatment of Patients With Epidermal Growth Factor Receptor Mutation Positive, Resectable Non-small Cell Lung Cancer | - | ||
| 3 | Active | A Phase III, Randomized, Double-Blind, Placebo-Controlled Study of Platinum Plus Pemetrexed Chemotherapy Plus Osimertinib Versus Platinum Plus Pemetrexed Chemotherapy Plus Placebo in Patients With EGFRm, Locally Advanced or Metastatic NSCLC Who Have Progressed Extracranially Following First-Line Osimertinib Therapy (COMPEL) | - | ||
BL-B01D1-307 NCT06382142 | 3 | Positive | Previously treated locally advanced or metastatic TNBC: izalontamab brengitecan vs chemotherapy | PFS and OS significantly improved at interim analysis (numbers presented ASCO 2026). | |
PANKU-Esophagus01 (BL-B01D1-305) NCT06304974 | 3 | Positive | Recurrent or metastatic oesophageal squamous cell carcinoma after PD-(L)1 inhibitor plus platinum chemotherapy: izalontamab brengitecan vs chemotherapy of physician's choice | OS and PFS significantly improved at interim analysis; numbers per ASCO 2026 presentation. | |
| 3 | Active | A Randomized Phase 3 Study of MRTX849 in Combination With Cetuximab Versus Chemotherapy in Patients With Advanced Colorectal Cancer With KRAS G12C Mutation With Disease Progression On or After Standard First-Line Therapy | - | ||
| 3 | Active | A Phase 3, Open-Label, Randomized Study of Amivantamab and Lazertinib in Combination With Platinum-Based Chemotherapy Compared With Platinum-Based Chemotherapy in Patients With EGFR-Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer After Osimertinib Failure | - | ||
BREAKWATER NCT04607421 | 3 | Positive | First-line BRAF V600E-mutant metastatic colorectal cancer: encorafenib + cetuximab + mFOLFOX6 (or FOLFIRI) vs chemotherapy ± bevacizumab | OS 30.3 vs 15.1 months (HR 0.49); PFS 12.8 vs 7.1 months. | |
HORIZON-Breast01 NCT05424835 | 3 | Positive | HER2+ metastatic breast cancer after trastuzumab and taxane (China): trastuzumab rezetecan (SHR-A1811) vs pyrotinib + capecitabine | PFS 30.6 vs 8.3 months, HR 0.22. | |
| 3 | Active | A Randomized, Open-label Phase 3 Study of Combination Amivantamab and Carboplatin-Pemetrexed Therapy, Compared With Carboplatin-Pemetrexed, in Patients With EGFR Exon 20ins Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer | - | ||
| ACE-Breast-02 | 3 | Positive | HER2+ advanced breast cancer after trastuzumab and taxane (China): ARX788 vs lapatinib + capecitabine | PFS 11.3 vs 8.2 months, HR 0.64. | |
HARMONi-A NCT05184712 | 3 | Positive | EGFR-mutant non-squamous NSCLC after progression on an EGFR TKI, China: ivonescimab or placebo plus pemetrexed and carboplatin | PFS 7.1 vs 4.8 months, HR 0.46. | |
LAURA NCT03521154 | 3 | Positive | Unresectable stage III EGFR-mutant NSCLC after chemoradiation: osimertinib until progression vs placebo | PFS HR 0.16. | |
CAIRO5 NCT02162563 | 3 | Mixed | Initially unresectable colorectal liver metastases, stratified by sidedness and RAS/BRAF status: a doublet plus bevacizumab, FOLFOXIRI plus bevacizumab, or a doublet plus panitumumab, with central resectability review every two months | FOLFOXIRI plus bevacizumab better than a doublet for right-sided or RAS/BRAF-mutant disease; panitumumab no better than bevacizumab for left-sided wild-type disease. | |
CodeBreaK 300 NCT05198934 | 3 | Positive | KRAS G12C colorectal cancer, previously treated: sotorasib + panitumumab vs standard of care | PFS HR 0.49. | |
FLAURA2 NCT04035486 | 3 | Positive | First-line EGFR-mutant NSCLC: osimertinib + chemotherapy vs osimertinib | PFS HR 0.62; OS HR 0.77. | |
FOxTROT ISRCTN83842641 | 3 | Positive | Six weeks of preoperative oxaliplatin-fluoropyrimidine chemotherapy plus 18 weeks after surgery, against 24 weeks after surgery alone, in radiologically staged T3-4 N0-2 M0 colon cancer, with a second randomisation to panitumumab in RAS wild-type tumours; the platform continues as FOxTROT 2 and 3 across 77 centres to April 2027 | Residual or recurrent disease within two years 16.9 percent with six weeks of preoperative chemotherapy against 21.5 percent with postoperative chemotherapy alone (rate ratio 0.72, 0.54 to 0.98, p = 0.037); complete resection 94 percent against 89 percent. | |
MARIPOSA NCT04487080 | 3 | Positive | First-line EGFR-mutant NSCLC: amivantamab + lazertinib vs osimertinib | PFS HR 0.70; OS HR 0.75. | |
| 3 | Positive | Locally advanced or metastatic KRAS wild-type pancreatic cancer: nimotuzumab plus gemcitabine versus placebo plus gemcitabine | Overall survival improved with nimotuzumab plus gemcitabine in KRAS wild-type disease. | ||
| 3 | Completed | A Multi-centre, Open-label, Randomized Clinical Trial Comparing the Efficacy and Safety of the Antibody-drug Conjugate SYD985 to Physician's Choice in Patients With HER2-positive Unresectable Locally Advanced or Metastatic Breast Cancer | - | ||
AENEAS NCT03849768 | 3 | Positive | First-line EGFR-mutant (exon 19 deletion or L858R) locally advanced or metastatic NSCLC, China: aumolertinib vs gefitinib | PFS 19.3 vs 9.9 months, HR 0.46. | |
FURLONG NCT03787992 | 3 | Positive | First-line EGFR-mutant (exon 19 deletion or L858R) locally advanced or metastatic NSCLC, China: furmonertinib vs gefitinib | PFS 20.8 vs 11.1 months, HR 0.44. | |
PARADIGM NCT02394795 | 3 | Positive | First-line RAS wild-type metastatic colorectal cancer: panitumumab + mFOLFOX6 vs bevacizumab + mFOLFOX6 | OS 37.9 vs 34.3 months (HR 0.82) in left-sided RAS wild-type disease. | |
| 3 | Active | A Multicenter, Randomized, Double-Blind Study of Erlotinib in Combination With Ramucirumab or Placebo in Previously Untreated Patients With EGFR Mutation-Positive Metastatic Non-Small Cell Lung Cancer | - | ||
ADAURA NCT02511106 | 3 | Positive | Adjuvant osimertinib 3 years after resection of stage IB-IIIA EGFR-mutant NSCLC | OS HR 0.49. | |
| Gefitinib vs gefitinib plus pemetrexed-carboplatin in EGFR-mutant lung cancer (Tata Memorial) | 3 | Positive | Untreated advanced EGFR-mutant non-small-cell lung cancer: gefitinib alone vs gefitinib plus pemetrexed and carboplatin | PFS 16 vs 8 months (HR 0.51); OS not reached vs 17 months (HR 0.45). | |
NALA NCT01808573 | 3 | Positive | HER2-positive metastatic breast cancer after two or more HER2-directed regimens: neratinib plus capecitabine against lapatinib plus capecitabine | Neratinib plus capecitabine improved progression-free survival over lapatinib plus capecitabine and reduced interventions for central nervous system disease; approved in February 2020. | |
New EPOC ISRCTN22944367 | 3 | Negative | KRAS wild-type resectable or suboptimally resectable colorectal liver metastases: perioperative chemotherapy with or without cetuximab | Median overall survival 55.4 months with cetuximab against 81.0 months without (hazard ratio 1.45). | |
| 3 | Active | A Phase III, Open Label, Randomised, Controlled, Multi-Centre Study To Assess the Efficacy and Safety of Savolitinib Versus Sunitinib in Patients With MET-Driven, Unresectable and Locally Advanced, Or Metastatic Papillary Renal Cell Carcinoma (PRCC) | - |
Mutation of the cysteine that osimertinib binds covalently; abolishes drug binding while EGFR stays active.
Amplified MET signals to PI3K/MAPK independently of EGFR.
Conversion to small-cell lung cancer (RB1/TP53 co-loss) or squamous histology; EGFR mutation persists but the cell no longer depends on it.
Relief of ERK-mediated negative feedback re-activates receptors within hours, producing new wild-type KRAS-GTP the drug cannot bind.
KEGG's breast cancer map lays out the three clinical subtypes as signalling routes: oestrogen receptor driving cyclin D and CDK4/6 in hormone-receptor-positive disease, HER2 driving PI3K/AKT and MAPK in HER2-positive disease, and EGFR, Notch, Wnt and BRCA defects in triple-negative disease. Each route has its own drug class.
Which nodes have drugs →This KEGG map shows how cancer cells rewire the handling of choline, a nutrient used to build cell membranes, so that growth signals and membrane building feed each other. It matters because the resulting build-up of phosphocholine is visible on MR spectroscopy and PET scans and is one of the metabolic hallmarks of cancer.
Which nodes have drugs →Most cancers have the wrong number of chromosomes and keep shuffling them at every division. This chaos fuels evolution and drug resistance, but it also stresses the cell and can trigger immune alarms, a double edge that researchers are trying to exploit.
Which nodes have drugs →This KEGG map traces the step-by-step genetic route from normal bowel lining to colorectal cancer: APC loss unleashes Wnt, KRAS mutation drives growth, then TP53 and TGF-beta/SMAD4 loss remove the last brakes, or alternatively mismatch repair fails and mutations pile up. Knowing which route a tumour took decides which drugs work.
Which nodes have drugs →Even when a drug wipes out 99% of a tumour, a few cells survive without any resistance mutation: they go quiet, stop dividing, and wait. These persisters are the seed of relapse. They are hard to kill precisely because they are not doing much, but they have their own weaknesses.
Which nodes have drugs →This KEGG map shows the two genetic roads to glioblastoma: primary tumours amplify EGFR and lose PTEN and p16, secondary tumours from lower-grade astrocytomas over-express PDGF and CDK4 and lose TP53 and RB. It explains why growth-factor and cell-cycle drugs are the main targeted options in brain tumours, and why paediatric low-grade gliomas with BRAF changes respond to MAPK inhibitors.
Which nodes have drugs →Under pressure from a drug that blocks its identity (the androgen receptor in prostate cancer, EGFR in lung cancer), a tumour can change what kind of cell it is, becoming a small-cell neuroendocrine cancer that no longer needs the blocked signal. It is the ultimate escape: not a new mutation in the engine, but a new engine.
Which nodes have drugs →KEGG's non-small cell lung cancer map shows a set of alternative on-switches (EGFR mutation, KRAS mutation, EML4-ALK, RET and MET alterations) that all feed the same RAS/ERK, PI3K/AKT and STAT relays, plus loss of the p16 and p53 brakes. Each on-switch now has its own targeted pill, which is why molecular testing comes before treatment.
Which nodes have drugs →KEGG's prostate cancer map centres on the androgen receptor, the hormone switch that prostate cells depend on, plus loss of PTEN and NKX3.1 that lets PI3K/AKT growth signalling run free. Hormone therapy, AR antagonists and now AKT inhibitors act on these two arms.
Which nodes have drugs →The RAS-MAPK pathway is the cell's 'divide' relay. A signal at the surface flips RAS on, which passes to RAF, MEK, and ERK, which tell the nucleus to make the cell divide. KRAS and BRAF mutations jam it in the on position.
Which nodes have drugs →Growth-factor receptors are antennas on the cell surface that pair up when a signal lands and switch on the growth relays inside. Cancers mutate, multiply, or fuse these antennas so they broadcast 'grow' with no signal at all. Most targeted drugs, antibodies and ADCs start here.
Which nodes have drugs →When a drug blocks a cancer's engine, the cancer has five ways back: change the part the drug binds, make more of it, take a side road, switch to a different engine altogether, or stop letting the drug in. Knowing which route a tumour took decides the next drug.
Which nodes have drugs →| Assay | Platform | Cut-off | Gates |
|---|---|---|---|
| cobas EGFR Mutation Test v2 Roche Molecular Systems · FDA CDx 2013 | PCR | Mutation detected (qualitative); plasma negative result should be reflexed to tissue | |
| therascreen EGFR RGQ PCR Kit QIAGEN · FDA CDx 2013 | PCR | Mutation detected (qualitative) | |
| therascreen KRAS RGQ PCR Kit QIAGEN · FDA CDx 2012 | PCR | Wild-type required for cetuximab or panitumumab (colorectal); G12C detected for sotorasib and adagrasib (NSCLC) | |
| therascreen BRAF V600E RGQ PCR Kit QIAGEN · FDA CDx 2020 | PCR | V600E detected (colorectal cancer, encorafenib plus cetuximab) | |
| FoundationOne CDx Foundation Medicine (Roche) · FDA CDx 2017 | NGS tissue | Per companion claim: EGFR, ALK, BRAF V600, ERBB2 amplification, KRAS wild-type, BRCA1/2 and HRR genes, PIK3CA, MET exon 14, RET, FGFR2 fusions, IDH1, NTRK fusions; MSI-high; TMB at least 10 mutations per megabase | |
| FoundationOne Liquid CDx Foundation Medicine (Roche) · FDA CDx 2020 | NGS plasma | Per companion claim: EGFR (osimertinib, erlotinib, gefitinib), ALK (alectinib), BRCA1/2 and ATM (olaparib, rucaparib), PIK3CA (alpelisib), FGFR3 (erdafitinib), NTRK and RET; negative plasma results reflex to tissue | |
| Guardant360 CDx Guardant Health · FDA CDx 2020 | NGS plasma | Per companion claim: EGFR (osimertinib), EGFR exon 20 insertions (amivantamab), KRAS G12C (sotorasib), ESR1 mutations (elacestrant), ERBB2 mutations (zongertinib); negative plasma reflexes to tissue | |
| Oncomine Dx Target Test Thermo Fisher Scientific · FDA CDx 2017 | NGS tissue | Per companion claim: BRAF V600E (dabrafenib plus trametinib), ROS1 fusions (crizotinib), EGFR (gefitinib), RET fusions (pralsetinib), MET exon 14 (tepotinib), EGFR exon 20 insertions | |
| EGFR pharmDx Agilent (Dako) · FDA CDx 2004 | IHC | Any EGFR membrane staining (historic requirement for cetuximab and panitumumab in colorectal cancer) |
| Cell line | Identifiers | Why it is used |
|---|---|---|
| PC-9 | CVCL_B260 · ACH-000779 | Exon 19 deletion; persister and resistance derivatives (PC-9/ER, PC-9/OR) are widely shared. |
| HCC827 | CVCL_2063 · ACH-000012 | Exon 19 deletion, amplified; MET-amplified resistant sublines (HCC827 GR). |
| NCI-H1975 | CVCL_1511 · ACH-000587 | L858R plus T790M; osimertinib-sensitive, first-generation-resistant. |
| NCI-H3255 | CVCL_6831 · ACH-000109 | L858R with amplification. |
| HCC4006 | CVCL_1269 · ACH-000066 | Exon 19 deletion; EMT-type resistance models. |
| NCI-H1650 | CVCL_1483 · ACH-000035 | Exon 19 deletion with PTEN loss; intrinsically TKI-resistant. |
| A-431 | CVCL_0037 · ACH-001328 | Vulval squamous line with massive EGFR amplification; the antibody and ADC binding standard. |
| Ba/F3 EGFR panels | not resolved | Engineered exon 20 insertion, C797S and other alleles in the IL-3-dependent Ba/F3 background. |
Why unresolved. C797S removes the covalent anchor of every third-generation TKI. Allosteric fourth-generation inhibitors exist only in early trials, while ADCs and bispecifics work regardless of the mutation but carry different toxicities.
What would answer it. A randomised comparison at osimertinib progression stratified by resistance mechanism (C797S, MET amplification, transformation), with biopsy or ctDNA at entry.
Why unresolved. FLAURA2 and MARIPOSA improve progression-free survival at the price of toxicity, and subgroup signals (brain metastases, TP53 co-mutation, detectable ctDNA) suggest the benefit is not uniform.
What would answer it. Prospective ctDNA- or co-mutation-stratified trials, or individual-patient meta-analysis of FLAURA2 and MARIPOSA, showing who gains overall survival.
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.
The dossier as machine-readable JSON, at /api/v1/dossiers/egfr.json: identifiers from HGNC, Ensembl, UniProt and ChEMBL, products with status, trials, pathways, hotspots, open questions and assays. The full entity record is in the open API at /api/v1/entities/egfr.json. Licence CC BY-NC 4.0.