Publication

Structural, biochemical, and clinical characterization of epidermal growth factor receptor (EGFR) exon 20 insertion mutations in lung cancer.

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Sci Transl Med2013PMID 24353160PMC3954775stubpubmedPublished

Abstract

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Linked entities

Linked entities (20)

How each link was made (MeSH, dictionary, registry reference, curation…) and whether it has been validated. Candidate links are not counted in entity statistics.

Validated 20

cancerLung Adenocarcinomacivic_curation1.00
cancerLung Non-Small Cell Carcinomacivic_curation1.00
drugAfatinibcivic_curation1.00
drugErlotinibcivic_curation1.00
drugGefitinibcivic_curation1.00
geneEGFRcivic_curation1.00
variantEGFR A763_Y764insFQEAcivic_curation1.00
variantEGFR A767_V769dupASVcivic_curation1.00
variantEGFR D770delinsGYcivic_curation1.00
variantEGFR D770_N771insGLcivic_curation1.00
variantEGFR D770_N771insNPGcivic_curation1.00
variantEGFR D770_N771insSVDcivic_curation1.00
variantEGFR H773_V774insHcivic_curation1.00
variantEGFR H773_V774insNPHcivic_curation1.00
variantEGFR L858Rcivic_curation1.00
variantEGFR M766_A767insAIcivic_curation1.00
variantEGFR M766_A767insASVcivic_curation1.00
variantEGFR P772_H773insYNPcivic_curation1.00
variantEGFR P772_V774insPHVcivic_curation1.00
variantEGFR Y764_V765insHHcivic_curation1.00

Curated evidence

Evidence citing this paper (30)

civicCuratedShowing 1–30 of 30 evidence items · levels, directions and significance as curated at the source; each row links to its CIViC record.

Therapy	Cancer	Type	Level	Direction · significance	Rating (1–5)	Status	Evidence	Source
EGFR A767_V769dupASV3
Erlotinib	Lung Adenocarcinoma	Predictive	C	Supports Resistance	—	accepted	EID4665 In a study of 19 non-small cell lung carcinoma patients with EGFR exon 20 insertion mutations and treated with erlotinib monotherapy, patients with EGFR A767_V769dupASV mutation (n=3) experienced prog… (full text at CIViC) PMID 24353160 · Yasuda et al., 2013 · Open in CIViC	civic
〃	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Sensitivity Response	2	submitted	EID5948 Ba/F3 cells transduced with EGFR A767_V769dupASV were IL3 growth independent, suggesting a driver mutation, and did not indicate sensitivity to erlotinib treatment (growth inhibition IC50=2.644 micro … (full text at CIViC) PMID 24353160 · Yasuda et al., 2013 · Open in CIViC	civic
Afatinib + GefitinibSubstitutes	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Does Not Support Sensitivity Response	3	submitted	EID5949 Ba/F3 cells transduced with EGFR A767_V769dupASV were IL3 growth independent, suggesting a driver mutation. Gefitinib growth inhibition IC50 in A767_V769dupASV transduced Ba/F3 cells was 2.685 micro … (full text at CIViC) PMID 24353160 · Yasuda et al., 2013 · Open in CIViC	civic
EGFR D770delinsGY2
Erlotinib	Lung Adenocarcinoma	Predictive	C	Supports Resistance	4	accepted	EID4801 In a study of 19 non-small cell lung carcinoma patients with EGFR exon 20 insertion mutation and treated with erlotinib monotherapy, patients with EGFR D770delinsGY mutation (n=2) experienced progress… (full text at CIViC) PMID 24353160 · Yasuda et al., 2013 · Open in CIViC	civic
〃	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	C	Supports Resistance	4	rejected	EID5942 2 patients with EGFR delD770insGY mutant lung adenocarcinoma were treated with first line erlotinib. A 76 year old female 6 pack year former smoker had progressive disease as best response with +38.1%… (full text at CIViC) PMID 24353160 · Yasuda et al., 2013 · Open in CIViC	civic
EGFR D770_N771insGL1
Erlotinib	Lung Adenocarcinoma	Predictive	C	Supports Resistance	4	accepted	EID4494 2 patients with EGFR D770_N771insGL mutant lung adenocarcinoma were treated with first line erlotinib. A 45 year old male never smoker had progressive disease as best response with +24% change to tar… (full text at CIViC) PMID 24353160 · Yasuda et al., 2013 · Open in CIViC	civic
EGFR H773_V774insNPH1
Erlotinib	Lung Adenocarcinoma	Predictive	C	Supports Resistance	3	accepted	EID4493 A 61 year old male never smoker with EGFR H773_V774insNPH mutant lung adenocarcinoma was treated with fourth line erlotinib and had progressive disease as best response, progression free survival of 1… (full text at CIViC) PMID 24353160 · Yasuda et al., 2013 · Open in CIViC	civic
EGFR P772_V774insPHV1
Erlotinib	Lung Adenocarcinoma	Predictive	C	Does Not Support Sensitivity Response	3	accepted	EID4803 A 57 year old male 10 packyear former smoker with lung adenocarcinoma with EGFR P772_V774insPHV mutation was given erlotinib as first line treatment, and had progressive disease as best response with … (full text at CIViC) PMID 24353160 · Yasuda et al., 2013 · Open in CIViC	civic
EGFR A763_Y764insFQEA3
Erlotinib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	B	Supports Sensitivity Response	2	submitted	EID5939 Out of a group of 19 EGFR exon 20 insertion NSCLC patients, 3 patients had EGFR M766_A767insASV mutation. One patient was 69 year old female neversmoker lung adenocarcinoma patient was given erlotini… (full text at CIViC) PMID 24353160 · Yasuda et al., 2013 · Open in CIViC	civic
〃	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Sensitivity Response	—	accepted	EID4497 In an in vitro study, Ba/F3 and BID007 cell lines expressing EGFR A763_Y764insFQEA demonstrated increased sensitivity to erlotinib treatment (IC50=0.048�M and 0.082�M, respectively), comparable to Ba/… (full text at CIViC) PMID 24353160 · Yasuda et al., 2013 · Open in CIViC	civic
Afatinib + GefitinibSubstitutes	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Sensitivity Response	3	submitted	EID5951 Ba/F3 cells transduced with EGFR A763_Y764insFQEA were IL3 growth independant, suggesting a driver mutation. Gefitinib growth inhibition IC50 in A763_Y764insFQEA transduced Ba/F3 cells was 0.174 micr… (full text at CIViC) PMID 24353160 · Yasuda et al., 2013 · Open in CIViC	civic
EGFR D770_N771insNPG2
Erlotinib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Resistance	—	submitted	EID4651 In an in vitro study, a Ba/F3 cell line expressing EGFR D770_N771insNPG demonstrated reduced sensitivity to erlotinib treatment (IC50=2.139�M), comparable to Ba/F3 cells expressing EGFR L858R and T790… (full text at CIViC) PMID 24353160 · Yasuda et al., 2013 · Open in CIViC	civic
Afatinib + GefitinibSubstitutes	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Does Not Support Sensitivity Response	3	accepted	EID5947 Ba/F3 cells transduced with EGFR D770_N771insNPG were IL3 growth independent, suggesting a driver mutation. Gefitinib growth inhibition IC50 in D770_N771insNPG transduced Ba/F3 cells was 3.356 micro … (full text at CIViC) PMID 24353160 · Yasuda et al., 2013 · Open in CIViC	civic
EGFR D770_N771insSVD2
Erlotinib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	C	Does Not Support Sensitivity Response	3	submitted	EID5941 2 patients with EGFR D770_N771insSVD positive lung adenocarcinoma were treated with erlotinib tyrosine kinase inhibitor as first line treatment. A 66 year old female never smoker had stable disease a… (full text at CIViC) PMID 24353160 · Yasuda et al., 2013 · Open in CIViC	civic
〃	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Resistance	—	accepted	EID4275 In an in vitro study, a Ba/F3 cell line expressing EGFR D770_N771insSVD demonstrated reduced sensitivity to erlotinib treatment (IC50=3.187�M), comparable to Ba/F3 cells expressing EGFR L858R and T790… (full text at CIViC) PMID 24353160 · Yasuda et al., 2013 · Open in CIViC	civic
EGFR E746_A750del3
Afatinib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Sensitivity Response	3	submitted	EID5946 HCC827 and PC9 NSCLC cell lines containing delE746_A750 mutation had growth inhibition IC50 with afatinib of 0.0010 and 0.0015 micro molar respectively. In comparison, NCI-H3255 EGFR L858R NSCLC cell … (full text at CIViC) PMID 24353160 · Yasuda et al., 2013 · Open in CIViC	civic
Erlotinib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Sensitivity Response	—	submitted	EID4203 In an in vitro study, HCC827 and PC9 cell lines expressing EGFR E746_A750del demonstrated increased sensitivity to erlotinib treatment (IC50=0.017�M and 0.071�M, respectively), comparable to NCI-H3255… (full text at CIViC) PMID 24353160 · Yasuda et al., 2013 · Open in CIViC	civic
〃	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Sensitivity Response	4	submitted	EID5945 HCC827 and PC9 NSCLC cell lines containing delE746_A750 mutation had growth inhibition IC50 with erlotinib of 0.017 and 0.071 micro molar respectively. In comparison, NCI-H3255 EGFR L858R NSCLC cell l… (full text at CIViC) PMID 24353160 · Yasuda et al., 2013 · Open in CIViC	civic
EGFR H773_V774insH2
Erlotinib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	C	Does Not Support Sensitivity Response	3	submitted	EID5940 A 74 year old female former smoker with 8 pack years and EGFR H773_V774insH lung adenocarcinoma patient was given erlotinib as second line treatment, and had progressive disease as best response with … (full text at CIViC) PMID 24353160 · Yasuda et al., 2013 · Open in CIViC	civic
〃	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Resistance	—	accepted	EID4276 In an in vitro study, a Ba/F3 cell line expressing EGFR H773_V774insH demonstrated reduced sensitivity to erlotinib treatment (IC50=3.902�M), comparable to Ba/F3 cells expressing EGFR L858R and T790M … (full text at CIViC) PMID 24353160 · Yasuda et al., 2013 · Open in CIViC	civic
EGFR L747_P753delinsS2
Erlotinib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Sensitivity Response	—	submitted	EID4267 In an in vitro study, a Ba/F3 cell line expressing EGFR L747_P753>S demonstrated increased sensitivity to erlotinib treatment (IC50=0.006�M), comparable to Ba/F3 cells expressing EGFR L858R (a known s… (full text at CIViC) PMID 24353160 · Yasuda et al., 2013 · Open in CIViC	civic
Afatinib + ErlotinibSubstitutes	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Sensitivity Response	3	submitted	EID5944 Ba/F3 cells transduced with EGFR delL747_P753insS were IL3 growth independant, suggesting driver mutation, and demonstrated sensitivity to erlotinib treatment (growth inhibition IC50=0.006 micro molar… (full text at CIViC) PMID 24353160 · Yasuda et al., 2013 · Open in CIViC	civic
EGFR L858R1
Erlotinib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Sensitivity Response	3	accepted	EID4286 In an in vitro study, Ba/F3 and NCI-H3255 cell lines expressing EGFR L858R demonstrated increased sensitivity to erlotinib treatment (IC50=0.006 and 0.068 µM). Sensitivity was determined by assessing … (full text at CIViC) PMID 24353160 · Yasuda et al., 2013 · Open in CIViC	civic
EGFR M766_A767insAI1
Erlotinib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Resistance	—	accepted	EID4799 In an in vitro study, a Ba/F3 cell line expressing EGFR M766_A767insAI demonstrated reduced sensitivity to erlotinib treatment (IC50=3.403�M), comparable to Ba/F3 cells expressing EGFR L858R and T790M… (full text at CIViC) PMID 24353160 · Yasuda et al., 2013 · Open in CIViC	civic
EGFR M766_A767insASV1
Erlotinib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	C	Does Not Support Sensitivity Response	3	accepted	EID5938 A 43 year old female neversmoker lung adenocarcinoma patient with EGFR M766_A767insASV mutation was given erlotinib as first line treatment, and had progressive disease as best response with -3.9% cha… (full text at CIViC) PMID 24353160 · Yasuda et al., 2013 · Open in CIViC	civic
EGFR P772_H773insH1
Erlotinib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Does Not Support Resistance	2	submitted	EID5950 In transduced cos7 cells, P772_H773insH cells showed increased sensitivity to erlotinib in comparison to cells with T790M resistance mutation, but decreased erlotinib sensitivity in comparison to L858… (full text at CIViC) PMID 24353160 · Yasuda et al., 2013 · Open in CIViC	civic
EGFR P772_H773insYNP1
Erlotinib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	C	Supports Resistance	3	accepted	EID4802 A 79 year old Asian male never smoker with not otherwise specified NSCLC harboring EGFR P772_H773insYNP mutation was given erlotinib as first line treatment, and had progressive disease as best respon… (full text at CIViC) PMID 24353160 · Yasuda et al., 2013 · Open in CIViC	civic
EGFR V769_D770insASV1
Erlotinib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	C	Supports Resistance	3	submitted	EID5943 A 60 year old female former smoker with 2 pack years and EGFR V769_D770insASV lung adenocarcinoma patient was given erlotinib as first line treatment, and had progressive disease as best response with… (full text at CIViC) PMID 24353160 · Yasuda et al., 2013 · Open in CIViC	civic
EGFR Y764_V765insHH2
Erlotinib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Resistance	—	accepted	EID4800 In an in vitro study, a Ba/F3 cell line expressing EGFR Y764_V765insHH demonstrated reduced sensitivity to erlotinib treatment (IC50=3.845�M), comparable to Ba/F3 cells expressing EGFR L858R and T790M… (full text at CIViC) PMID 24353160 · Yasuda et al., 2013 · Open in CIViC	civic
Gefitinib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	C	Does Not Support Sensitivity Response	3	submitted	EID5937 A 66 year old male with 10 pack year smoking history and lung adenocarcinoma with EGFR Y764_V765insHH mutation was given gefitinib as first line treatment, and had stable disease as best response with… (full text at CIViC) PMID 24353160 · Yasuda et al., 2013 · Open in CIViC	civic