EGFR mutation testing in lung cancer: a review of available methods and their use for analysis of tumour tissue and cytology samples
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...Targeted methods include polymerase chain reaction (PCR) -based targeted methods, such as ARMS (Amplification Refractory Mutation SystemARMS) and SmartAMP (Smart Amplification Process).(85,86) Gefitinib, erlotinib, and afatinib are currently...
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References
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"EGFR mutation testing in lung cance..." refers background in this paper
...While fragment length analysis is used widely in practice, it can only detect insertions or deletions and does not allow detection of point mutations in EGFR....
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...4 Two types of mutation—short in-frame deletions in exon 19, clustered around the amino-acid residues 747–750 and a specific exon 21 point mutation (L858R)—have been reported to comprise up to 90% of all activating EGFR mutations.(3) 4 13 Other activating mutations include point mutations in exon 18 (including mutations in codon 719) and point mutations and in-frame insertions in exon 20 (including T790M)....
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...The conformational change seen in the TK domain of mutated EGFRs increases the activation of the domain and its affinity for ATP (and EGFR TKIs) compared with wild-type EGFR.(3)The resulting increase in binding of EGFR TKIs produces greater inhibition of the domain and blocking of signal transduction pathways implicated in the proliferation and survival of cancer cells....
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...Gefitinib also improved PFS versus chemotherapy in two Phase III trials performed solely in patients with EGFR mutationpositive advanced NSCLC.6 7 In addition, in two Phase III erlotinib trials that recruited EGFR mutation-positive patients, PFS was significantly increased with first-line erlotinib relative to chemotherapy.9 10 As a result of these data, the accurate identification of patients who might benefit from EGFR TKI therapy has become an important step in the treatment-decision pathway for advanced NSCLC.9 12 Mutations associated with enhanced sensitivity to EGFR TKIs are found in exons 18–21 of the TK domain of EGFR.3 4 Two types of mutation—short in-frame deletions in exon 19, clustered around the amino-acid residues 747–750 and a specific exon 21 point mutation (L858R)—have been reported to comprise up to 90% of all activating EGFR mutations.3 4 13 Other activating mutations include point mutations in exon 18 (including mutations in codon 719) and point mutations and in-frame insertions in exon 20 (including T790M)....
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...In patients with wild-type EGFR, carboplatin/paclitaxel was associated with significantly longer PFS than gefitinib.8 The conformational change seen in the TK domain of mutated EGFRs increases the activation of the domain and its affinity for ATP (and EGFR TKIs) compared with wild-type EGFR.3The resulting increase in binding of EGFR TKIs produces greater inhibition of the domain and blocking of signal transduction pathways implicated in the proliferation and survival of cancer cells....
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"EGFR mutation testing in lung cance..." refers background in this paper
...In patients with wild-type EGFR, carboplatin/paclitaxel was associated with significantly longer PFS than gefitinib.(8) The conformational change seen in the TK domain of mutated EGFRs increases the activation of the domain and its affinity for ATP (and EGFR TKIs) compared with wild-type EGFR....
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4,829 citations
"EGFR mutation testing in lung cance..." refers background in this paper
...Key messages ▸ The development of targeted EGFR mutation testing methods and commercially available test kits has enabled sensitive, rapid and robust analysis of clinical samples from patients with NSCLC. ▸ The use of screening methods, either used alone or in conjunction with targeted methods, enables the detection of more rare and novel EGFR mutations....
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...Gefitinib also improved PFS versus chemotherapy in two Phase III trials performed solely in patients with EGFR mutationpositive advanced NSCLC.(6) 7 In addition, in two Phase III erlotinib trials that recruited EGFR mutation-positive patients, PFS was significantly increased with first-line erlotinib relative to chemotherapy....
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...Gefitinib also improved PFS versus chemotherapy in two Phase III trials performed solely in patients with EGFR mutationpositive advanced NSCLC.6 7 In addition, in two Phase III erlotinib trials that recruited EGFR mutation-positive patients, PFS was significantly increased with first-line erlotinib relative to chemotherapy.9 10 As a result of these data, the accurate identification of patients who might benefit from EGFR TKI therapy has become an important step in the treatment-decision pathway for advanced NSCLC.9 12 Mutations associated with enhanced sensitivity to EGFR TKIs are found in exons 18–21 of the TK domain of EGFR.3 4 Two types of mutation—short in-frame deletions in exon 19, clustered around the amino-acid residues 747–750 and a specific exon 21 point mutation (L858R)—have been reported to comprise up to 90% of all activating EGFR mutations.3 4 13 Other activating mutations include point mutations in exon 18 (including mutations in codon 719) and point mutations and in-frame insertions in exon 20 (including T790M)....
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...Both screening and targeted methods have been used to identify EGFR mutations in clinical trials of EGFR TKIs in patients with advanced NSCLC.6–10 14–16 84 These trials were not identified by our search due to our focus on method comparison studies....
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