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Abstract
The majority of non-small cell (NSC) lung cancers express epidermal growth factor receptor (EGFR). Many studies have evaluated the clinical effect from targeted therapy achieved by blocking EGFR in patients with NSC lung cancer. Treatment of biologically unselected patients with NSC lung cancer with two reversible quinazole EGFR inhibitors, gefitinib and erlotinib, gave negative results in all controlled trials but one. Ten percent to 20% of patients with NSC lung cancers have somatic mutations in EGFR, and these patients have a significantly higher response rate (73%) to treatment with EGFR inhibitors than patients with wild-type EGFR (10%). Patients with Asian background, women, non-smokers, and patients with adenocarcinoma had higher response rates than other patients, and the differences may be due to an association between the clinical characteristics and EGFR mutations. Further studies are needed to fully evaluate the effect of EGFR inhibitor-treatment for subgroups of patients with NSC lung cancer with favorable biological and clinical characteristics.
Key words :
| ABBREVIATIONS | ||
| ABCG2 | = | ATP-binding cassette subfamily G member 2 |
| ABL1 | = | v-abl Abelson murine leukemia viral oncogene homolog 1 (alias ABL) |
| AKT1 | = | v-akt murine thymoma viral oncogene homolog 1 |
| ATP | = | adenosine 5-triphosphate |
| BAD | = | BCL2-antagonist of cell death |
| BCL2 | = | B-cell CLL/lymphoma 2 |
| BIRC5 | = | bacuviral IAP repeat containing protein 5 (alias survivin) |
| CHD1 | = | cadherin 1, type 1 (alias E-cadherin [epithelial]) |
| CCND | = | cyclin D |
| CDKN1B | = | cyclin-dependent kinase inhibitor 1B |
| CI | = | confidence interval |
| E2F | = | E2F transcription factor |
| EGFR/ERBB | = | epidermal growth factor receptor(s) |
| EGFRvIII | = | EGFR variant III |
| ERBB2/NEU/HER-2 | = | v-erb-b2 erythroblastic leukemia viral oncogene homolog2, neuro/glioblastoma derived oncogene homolog (avian) |
| FISH | = | fluorescence in situ hybridization |
| FOS | = | v-fos FBJ murine osteosarcoma viral oncogene homolog |
| FOXO3A (3B) | = | forkhead box O3A (3B) (alias forkhead) |
| GRB2 | = | growth factor receptor binding protein 2 |
| GSK3A | = | glycogen synthase kinase 3-alpha |
| JAK | = | janus kinase 1 (a protein tyrosine kinase) |
| JUN | = | v-jun sarcoma virus 17 oncogene homolog (avian) |
| KRAS | = | v-ki-ras2 Kirsten rat sarcoma viral oncogene homolog |
| MAP2K1 | = | mitogen-activated protein kinase kinase 1 (alias MEK1/2) |
| MAPK1 | = | mitogen-activated protein kinase 1 (alias ERK 1/2) |
| NSC | = | non-small cell |
| PCR | = | polymerase chain reaction |
| P-AKT1 | = | phosphorylated AKT1 |
| p-MAPK1 | = | phosphorylated MAPK1 |
| PIK3 | = | phosphoinositide-3-kinase |
| PI3,4P2 | = | phosphoinositide-3,4-diphosphate |
| PI3,4,5P3 | = | phosphoinositide-3,4,5-triphosphate |
| PTEN | = | phosphatase and tensin homolog |
| RAF1 | = | v-raf-1 murine leukemia viral oncogene homolog 1 |
| RFLP | = | restriction fragment length polymorphism |
| SH2 domains | = | v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian)(SRC) homolog-2 domains |
| SOS1 | = | son of sevenless 1, homolog 1 |
| SRC | = | v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian) |
| STAT | = | signal transducer and activator of transcription |
| TGFA | = | transforming growth factor-α |
| VEGFR | = | vascular endothelial growth factor (receptor) |
| YWHAA | = | tyrosine 3-monooxygenase/tryptophan 5-monooxygenase-activating protein alpha polypeptide (alias 14-3-3 alpha). |
| ABBREVIATIONS | ||
| ABCG2 | = | ATP-binding cassette subfamily G member 2 |
| ABL1 | = | v-abl Abelson murine leukemia viral oncogene homolog 1 (alias ABL) |
| AKT1 | = | v-akt murine thymoma viral oncogene homolog 1 |
| ATP | = | adenosine 5-triphosphate |
| BAD | = | BCL2-antagonist of cell death |
| BCL2 | = | B-cell CLL/lymphoma 2 |
| BIRC5 | = | bacuviral IAP repeat containing protein 5 (alias survivin) |
| CHD1 | = | cadherin 1, type 1 (alias E-cadherin [epithelial]) |
| CCND | = | cyclin D |
| CDKN1B | = | cyclin-dependent kinase inhibitor 1B |
| CI | = | confidence interval |
| E2F | = | E2F transcription factor |
| EGFR/ERBB | = | epidermal growth factor receptor(s) |
| EGFRvIII | = | EGFR variant III |
| ERBB2/NEU/HER-2 | = | v-erb-b2 erythroblastic leukemia viral oncogene homolog2, neuro/glioblastoma derived oncogene homolog (avian) |
| FISH | = | fluorescence in situ hybridization |
| FOS | = | v-fos FBJ murine osteosarcoma viral oncogene homolog |
| FOXO3A (3B) | = | forkhead box O3A (3B) (alias forkhead) |
| GRB2 | = | growth factor receptor binding protein 2 |
| GSK3A | = | glycogen synthase kinase 3-alpha |
| JAK | = | janus kinase 1 (a protein tyrosine kinase) |
| JUN | = | v-jun sarcoma virus 17 oncogene homolog (avian) |
| KRAS | = | v-ki-ras2 Kirsten rat sarcoma viral oncogene homolog |
| MAP2K1 | = | mitogen-activated protein kinase kinase 1 (alias MEK1/2) |
| MAPK1 | = | mitogen-activated protein kinase 1 (alias ERK 1/2) |
| NSC | = | non-small cell |
| PCR | = | polymerase chain reaction |
| P-AKT1 | = | phosphorylated AKT1 |
| p-MAPK1 | = | phosphorylated MAPK1 |
| PIK3 | = | phosphoinositide-3-kinase |
| PI3,4P2 | = | phosphoinositide-3,4-diphosphate |
| PI3,4,5P3 | = | phosphoinositide-3,4,5-triphosphate |
| PTEN | = | phosphatase and tensin homolog |
| RAF1 | = | v-raf-1 murine leukemia viral oncogene homolog 1 |
| RFLP | = | restriction fragment length polymorphism |
| SH2 domains | = | v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian)(SRC) homolog-2 domains |
| SOS1 | = | son of sevenless 1, homolog 1 |
| SRC | = | v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian) |
| STAT | = | signal transducer and activator of transcription |
| TGFA | = | transforming growth factor-α |
| VEGFR | = | vascular endothelial growth factor (receptor) |
| YWHAA | = | tyrosine 3-monooxygenase/tryptophan 5-monooxygenase-activating protein alpha polypeptide (alias 14-3-3 alpha). |