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Variants & evidence
1,206 evidence items mapped to this entity or its descendants, grouped by molecular profile, then therapy. 50 items per page.
| Therapy | Cancer | Type | Level | Direction · significance | Rating (1–5) | Status | Evidence | Source |
|---|---|---|---|---|---|---|---|---|
| EGFR S768N2 | ||||||||
| Erlotinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Resistance | — | submitted | EID4271The S768N mutation was first reported in a cohort of African American patients with non-small cell lung cancer (NSCLC). Classical EGFR mutations such as the L858R mutation and exon 19 deletions, foun… (full text at CIViC) PMID 19786660 · Leidner et al., 2009 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | D | Supports Resistance | — | submitted | EID4272Cells expressing EGFR harboring the S768N mutation were resistant to erlotinib treatment of up to 3uM, as measured using an in vitro fibril formation assay. This contrasts with cells expressing the L8… (full text at CIViC) PMID 21132006 · Harada et al., 2011 · Open in CIViC | civic |
| EGFR S784F2 | ||||||||
| Erlotinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | C | Supports Resistance | — | submitted | EID4469In a pulmonary undifferentiated non-small cell lung cancer patient harboring EGFR S784F mutation, EGFR S784F was reported to be resistant to erlotinib treatment. The patient was initially treated with… (full text at CIViC) PMID 21841502 · De Pas et al., 2011 · Open in CIViC | civic |
| Gefitinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | C | Does Not Support Sensitivity Response | 3 | submitted | EID4235In a study, 1 participant with stage IV lung adenocarcinoma was sequenced at EGFR exons 18 to 21 and was found to have S784F mutation, and was treated with the 1st generation TKI gefitinib. The patien… (full text at CIViC) PMID 21531810 · Wu et al., 2011 · Open in CIViC | civic |
| SEPTIN14 Fusion2 | ||||||||
| (oncogenic) | Lung Adenocarcinoma | Oncogenic | C | Supports Oncogenicity | 2 | submitted | EID11005A case report of a 56 year old male with metastatic lung adenocarcinoma to the leptomeninges, in whom two rare EGFR::SEPT14 fusions were identified. On second recurrence, NGS was performed on the CSF,… (full text at CIViC) PMID 34486539 · Zheng et al., 2022 · Open in CIViC | civic |
| Carboplatin + Icotinib + Paclitaxel LiposomeSequential | Lung Adenocarcinoma | Predictive | C | Supports Sensitivity Response | 2 | submitted | EID10914Case report of a 62-year-old woman with lung adenocarcinoma. She underwent treatment with liposome-paclitaxel and carboplatin. They detected EGFR-SEPT14 fusion (N-terminal amino acids of EGFR and C-te… (full text at CIViC) PMID 31345345 · Zhu et al., 2019 · Open in CIViC | civic |
| SHC1 Fusion1 | ||||||||
| (oncogenic) | Lung Adenocarcinoma | Oncogenic | B | Supports Oncogenicity | 3 | submitted | EID12361This article identified in-frame EGFR-SHC1 fusions in a 61-year-old male smoker with stage IIIA NSCLC, retaining functional kinase domains. RNA-based NGS fusion assays was used for detecting actionabl… (full text at CIViC) PMID 31382039 · Pan et al., 2019 · Open in CIViC | civic |
| SUMF2 Fusion1 | ||||||||
| (prognostic) | Lung Adenocarcinoma | Prognostic | B | Supports Poor Outcome | 3 | submitted | EID12388In this study, the authors employed next-generation sequencing (NGS) to compare the genetic profiles of lung adenocarcinoma (LUAD) patients with and without adrenal metastases. An EGFR-SUMF2 fusion wa… (full text at CIViC) PMID 39673828 · Pan et al., 2025 · Open in CIViC | civic |
| EGFR T725M1 | ||||||||
| Unspecified therapy | Lung Adenocarcinoma | Predictive | D | Supports N/A | 3 | submitted | EID1973T725M and L861R are rare cancer-associated mutations and increase EGFR activity in the absence of the activating EGF ligand in cell-based assays PMID 24743239 · U et al., 2014 · Open in CIViC | civic |
| EGFR T790M41 | ||||||||
| (prognostic) | Lung Non-Small Cell CarcinomaCURATED_BROADER | Prognostic | B | Supports Poor Outcome | 4 | accepted | EID369In NSCLC patients with T790M and another activating mutations, their progression free survival is shorter compared to those who do not possess T790M mutation. PMID 24623981 · Ding et al., 2014 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Prognostic | B | Supports Poor Outcome | 4 | accepted | EID370Patients with NSCLC harboring EGFR T790M mutation have statistically worse overall survival compared to patients with L858R or other exon 19 activating mutations. PMID 24729716 · Li et al., 2014 · Open in CIViC | civic |
| (oncogenic) | Lung Non-Small Cell CarcinomaCURATED_BROADER | Oncogenic | D | |||||
Data updated 9 hours agoSource updated unknownsource: civic (CC0)
Evidence levels, directions and ratings are those assigned by CIViC curators. "Submitted" items have not completed curation review. This is not treatment guidance.
| Supports Oncogenicity |
| 3 |
| submitted |
EID12922In this study, the authors evaluated the functional effects of the EGFR T790M variant in non-small cell lung cancer (NSCLC) by expressing wild-type and mutant EGFR in HEK293T, COS-7, and human bronchi… (full text at CIViC) PMID 17510392 · Vikis et al., 2007 · Open in CIViC |
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| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Oncogenic | D | Supports Oncogenicity | 3 | submitted | EID12923In this study, the authors evaluated the catalytic activity of epidermal growth factor receptor (EGFR) variants associated with non-small cell lung cancer (NSCLC) using purified recombinant EGFR intra… (full text at CIViC) PMID 17332364 · Mulloy et al., 2007 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Oncogenic | D | Supports Oncogenicity | 3 | submitted | EID12924In this study, the authors evaluated the oncogenic and signaling effects of the EGFR T790M variant in non-small cell lung cancer (NSCLC), both alone and in cis with activating EGFR variants, including… (full text at CIViC) PMID 17671201 · Godin-Heymann et al., 2007 · Open in CIViC | civic |
| 〃 | Lung Adenocarcinoma | Oncogenic | D | Supports Oncogenicity | 3 | accepted | EID12925In this study, the authors investigated the role of the EGFR T790M mutation using inducible mouse lung tumor models expressing T790M alone or in combination with the activating L858R mutation. They de… (full text at CIViC) PMID 17726540 · Regales et al., 2007 · Open in CIViC | civic |
| Afatinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Resistance | 4 | accepted | EID1863Patients with advanced NSCLC and acquired resistance to EGFR TKI (gefitinib or erlotinib) were analyzed for T790M mutations. Of the 70 patients analyzed, 36 (51%) had the T790M mutation and 34 (49%) … (full text at CIViC) PMID 24035188 · Sun et al., 2013 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 2 | accepted | EID2163In an in vitro study using NCI-H1666 cells (wildtype EGFR) and NCI-H1975 cells (EGFR-L858R/T790M), inhibition of cell growth was used as an assay to determine sensitivity to tyrosine kinase inhibitor … (full text at CIViC) PMID 18408761 · Li et al., 2008 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 2 | accepted | EID2164In an in vitro study using purified EGFR protein, kinase activity was assayed and compared for wildtype EGFR, EGFR-T790M and EGFR-T790M/L858R using both reversible and irreversible TKI drugs. EFGR pro… (full text at CIViC) PMID 21732342 · Cha et al., 2012 · Open in CIViC | civic |
| Canertinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 2 | accepted | EID2165In an in vitro study using NCI-H1666 cells (wildtype EGFR) and NCI-H1975 cells (EGFR-L858R/T790M), inhibition of cell growth was used as an assay to determine sensitivity to tyrosine kinase inhibitor … (full text at CIViC) PMID 18408761 · Li et al., 2008 · Open in CIViC | civic |
| Brigatinib + Cetuximab + PanitumumabCombination | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 4 | submitted | EID4836Currently, there are no effective therapeutic strategies to overcome the C797S/T790M/activating-mutation (triple-mutation)-mediated EGFR-TKI resistance to Osimertinib. In the present study, we identif… (full text at CIViC) PMID 28287083 · Uchibori et al., 2017 · Open in CIViC | civic |
| Dacomitinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Resistance | 4 | accepted | EID240In Lung Cancer patients with acquired resistance to Dacomitinib (PF00299804), MET amplification and EGFR T790M were found to be the primary drivers of resistance. PMID 21430269 · Sequist et al., 2011 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 3 | accepted | EID2161In an in vitro study using NCI-H322 cells (wildtype EGFR) and NCI-H1975 cells (EGFR-L858R/T790M), inhibition of cell growth was used as an assay to determine sensitivity to irreversible tyrosine kinas… (full text at CIViC) PMID 18089823 · Engelman et al., 2007 · Open in CIViC | civic |
| Erlotinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | A | Supports Resistance | 5 | accepted | EID238The T790M mutation in EGFR has been shown to confer resistance to the tyrosine kinase inhibitor erlotinib, and patients harboring this mutation that are placed on the drug are likely to relapse. PMID 25668228 · Denis et al., 2015 · Open in CIViC | civic |
| 〃 | Lung Adenocarcinoma | Predictive | C | Supports Resistance | 3 | submitted | EID12945A 53-year-old Chinese man and lifelong non-smoker presented with chest tightness and pain. CT scans revealed multiple small lung nodules in the right lower lobe were seen with CT scan. Biopsy confirme… (full text at CIViC) PMID 38074875 · Xiang et al., 2023 · Open in CIViC | civic |
| 〃 | Lung Adenocarcinoma | Predictive | C | Supports Resistance | — | submitted | EID3806In a lung adenocarcinoma patient with EGFR E746_A751>A (a known erlotinib sensitizing mutation) and EGFR T790M co-mutation treated with erlotinib monotherapy, EGFR T790M was associated with disease pr… (full text at CIViC) PMID 17085664 · Balak et al., 2006 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | C | Supports Resistance | — | submitted | EID3807In a study of 6 patients with progressive non-small cell lung cancer during gefitinib or erlotinib therapy, comparison of DNA sequences from the original diagnostic biopsy specimen and the second bio… (full text at CIViC) PMID 15737014 · Pao et al., 2005 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | — | submitted | EID3801In an in vitro study, a Ba/F3 cell line expressing EGFR S752_I759del demonstrated increased sensitivity to erlotinib treatment (IC50=33nM), comparable to Ba/F3 cells expressing EGFR L858R (a known sen… (full text at CIViC) PMID 17877814 · de Gunst et al., 2007 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | D | Supports Resistance | — | submitted | EID3808In an in vitro study, a NCI-H1975 cell line expressing EGFR L858R and EGFR T790M co-mutation, EGFR T790M was associated with reduced sensitivity to erlotinib treatment compared to QG56 cells expressin… (full text at CIViC) PMID 25853010 · Abourbeh et al., 2015 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | D | Supports Resistance | — | submitted | EID3809In an in vitro study, a MCF-7 cell line expressing EGFR L858R and T790M co-mutation demonstrated resistance to erlotinib treatment, compared to MCF-7 cells expressing a known erlotinib sensitizing mut… (full text at CIViC) PMID 21132006 · Harada et al., 2011 · Open in CIViC | civic |
| Erlotinib + PemetrexedCombination | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | C | Supports Sensitivity Response | 3 | accepted | EID277In an NSCLC patient initially with L858R mutation, pemetrexed and cisplatin combination treatment was followed by erlotinib treatment. A slow progression developed which was found to be positive for L… (full text at CIViC) PMID 24636847 · Li et al., 2014 · Open in CIViC | civic |
| Gefitinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Resistance | 3 | accepted | EID239In non-small cell lung cancer, the appearance of T790M mutation leads to resistance to gefitinib. PMID 15728811 · Kobayashi et al., 2005 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Resistance | 3 | accepted | EID2159In a study of 14 patients with progressive non-small cell lung cancer during gefitinib treatment, comparison of DNA sequences from the original diagnostic biopsy specimen and the post-treatment biopsy… (full text at CIViC) PMID 17020982 · Kosaka et al., 2006 · Open in CIViC | civic |
| Erlotinib + GefitinibSubstitutes | Lung Adenocarcinoma | Predictive | B | Supports Resistance | 3 | accepted | EID1391155 patients with lung adenocarcinomas underwent rebiopsy and genotyping (EGFR, AKT1, BRAF, ERBB2, KRAS, MEK1, NRAS, PIK3CA and FISH for MET and HER2) after the development of acquired resistance to E… (full text at CIViC) PMID 23470965 · Yu et al., 2013 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Resistance | 3 | accepted | EID166748 tumor samples from 41 patients with EGFR mutant lung adenocarcinoma that were resistant to tyrosine kinase inhibition by gefitinib (n=1) or erlotinib (n=40) underwent next generation sequencing (NG… (full text at CIViC) PMID 27304188 · Belchis et al., 2016 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | C | Supports Resistance | 4 | accepted | EID2158In a study of 6 patients with progressive non-small cell lung cancer during gefitinib or erlotinib therapy, comparison of DNA sequences from the original diagnostic biopsy specimen and a post-treatmen… (full text at CIViC) PMID 15737014 · Pao et al., 2005 · Open in CIViC | civic |
| Lapatinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | D | Supports Resistance | 4 | accepted | EID2160In an in vitro study using NCI-H1666 cells (wildtype EGFR) and NCI-H1975 cells (EGFR-L858R/T790M), inhibition of cell growth was used as an assay to determine sensitivity to reversible tyrosine kinase… (full text at CIViC) PMID 18408761 · Li et al., 2008 · Open in CIViC | civic |
| Lazertinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID12783An in vitro study treated Ba/F3 murine cells (IL-3 dependent lymphocyte model) to afatinib, a second-generation tyrosine kinase inhibitor (TKI), for several weeks. Secondary resistant mutations to afa… (full text at CIViC) PMID 40940797 · Oiki et al., 2025 · Open in CIViC | civic |
| Mitogen-Activated Protein Kinase Kinase Inhibitor + Naquotinib + OsimertinibSequential | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | D | Supports Resistance | 3 | submitted | EID6318Clinical study confirmed a beneficial effect from the combination therapy of MEK inhibitors and naquotinib. Inhibited cell proliferation in both naquotinib-resistant and osimertinib-resistant cells, … (full text at CIViC) PMID 29386539 · Ninomiya et al., 2018 · Open in CIViC | civic |
| Neratinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 2 | accepted | EID2162The NSCLC cell line NCI-H1975 carrying the EGFR T790M mutation was resistant to erlotinib but showed increased sensitivity to HKI-272 (neratinib, IC50: 0.29 μmol/L). In an in vitro study Ba/F3 cells t… (full text at CIViC) PMID 16818618 · Shimamura et al., 2006 · Open in CIViC | civic |
| Osimertinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 5 | accepted | EID1592Osimertinib has been approved for the treatment of EGFR T790M mutant NSCLC. PMID 26729184 · Greig, 2016 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 5 | accepted | EID1867Randomized, international, open-label, phase 3 trial (NCT02151981) in 419 patients with T790M-positive advanced NSCLC and disease progression after first-line EGFR-TKI therapy. Patients were randomize… (full text at CIViC) PMID 27959700 · Mok et al., 2017 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID965This phase I/II trial (NCT01802632) involved 253 non-small cell lung cancer patients with activating EGFR mutations, who had progressed on first generation tyrosine kinase inhibitor treatment, and wer… (full text at CIViC) PMID 25923549 · Jänne et al., 2015 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID966This study summarized 9 EGFR-mutant patients from two clinical trials involving rociletinib (NCT01526928) and subsequent osimertinib (NCT01802632). 8 were T790M-positive prior to treatment with osimer… (full text at CIViC) PMID 26720284 · Sequist et al., 2016 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | — | rejected | EID2166In a prospective study (NCT01802632) of 253 locally advanced or metastatic, non-small cell lung cancer patients, patients with EGFR T790M mutations treated with osimertinib were associated with improv… (full text at CIViC) PMID 25923549 · Jänne et al., 2015 · Open in CIViC | civic |
| 〃 | Lung Squamous Cell Carcinoma | Predictive | C | Supports Sensitivity Response | 4 | submitted | EID12066A 57-year old male with no significant smoking history presented with lung squamous cell carcinoma in the right lung. Oncomine Dx Target Test was done and revealed EGFR exon 19 deletion and de novo EG… (full text at CIViC) PMID 37641467 · Maeda et al., 2023 · Open in CIViC | civic |
| 〃 | Lung Adenocarcinoma | Predictive | C | Supports Sensitivity Response | 2 | accepted | EID2157In a lung adenocarcinoma patient harboring an EGFR E746_A750 mutation and an acquired EGFR T790M co-mutation, EGFR T790M was associated with sensitivity to osimertinib monotherapy. Prior to the develo… (full text at CIViC) PMID 26269204 · Planchard et al., 2015 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 3 | accepted | EID963Cell line, xenograft, and transgenic models were used to establish Osimertinib as an inhibitor of both EGFR mutation sensitizing (L858M, del exon 19) and T790M resistance mutants. Preclinically, the d… (full text at CIViC) PMID 24893891 · Cross et al., 2014 · Open in CIViC | civic |
| Osimertinib + RociletinibSubstitutes | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 2 | accepted | EID967For cells harboring EGFR T790M mutation, osimertinib and rociletinib showed potent inhibition compared to erlotinib or afatinib. This study performed drug response assays using five human NSCLC cell l… (full text at CIViC) PMID 26515464 · Hirano et al., 2015 · Open in CIViC | civic |
| Rociletinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID646In a phase1-2 study, patients with the T790M mutation were more sensitive to rocelitinib in comparison to patients with T790M-negative NSCLC. PMID 25923550 · Sequist et al., 2015 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Does Not Support Sensitivity Response | 4 | rejected | EID5709Recently, the development of the third-generation epidermal growth factor receptor-small molecule inhibitor (EGFR-TKI) rociletinib had failed. in May 2016, after receiving a negative reply from the … (full text at CIViC) PMID 27785053 · Van Der Steen et al., 2016 · Open in CIViC | civic |