Review of the Treatment of Non-Small Cell Lung Cancer with Gefitinib

Araki, Takuya; Yashima, Hideaki; Shimizu, Kimihiro; Aomori, Tohru; Hashita, Tadahiro; Kaira, Kyoichi; Nakamura, Tomonori; Yamamoto, Keiji

doi:10.4137/cmo.s7340

Cited by 34 publications

(25 citation statements)

References 98 publications

(200 reference statements)

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“…As shown in Figure 1C, the kinase activity inhibition IC 50 for Gefitinib was nearly 21 nM (Figure 1C), which is consistent with a previous report [21]. The inhibition IC 50 for WB-308 was about 43 nM (Figure 1C), suggesting WB-308 directly inhibited the kinase activity of EGFR at a concentration similar to Gefitinib.…”

Section: Resultssupporting

confidence: 90%

Inhibition of non-small cell lung cancer (NSCLC) growth by a novel small molecular inhibitor of EGFR

Deng

et al. 2015

Oncotarget

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The epidermal growth factor receptor (EGFR) is a therapeutic target (oncotarget) in NSCLC. Using in vitro EGFR kinase activity system, we identified a novel small molecule, WB-308, as an inhibitor of EGFR. WB-308 decreased NSCLC cell proliferation and colony formation, by causing G2/M arrest and apoptosis. Furthermore, WB-308 inhibited the engraft tumor growths in two animal models in vivo (lung orthotopic transplantation model and patient-derived engraft mouse model). WB-308 impaired the phosphorylation of EGFR, AKT, and ERK1/2 protein. WB-308 was less cytotoxic than Gefitinib. Our study suggests that WB-308 is a novel EGFR-TKI and may be considered to substitute for Gefitinib in clinical therapy for NSCLC.

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Section: Resultssupporting

confidence: 90%

Inhibition of non-small cell lung cancer (NSCLC) growth by a novel small molecular inhibitor of EGFR

Deng

et al. 2015

Oncotarget

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“…Of particular importance, these mutations are known as predictors of a favorable clinical outcome in response to treatment with EGFR-tyrosine kinase inhibitors (EGFR-TKIs) (1,2). Although ~80% of NSCLC patients with drug-sensitive EGFR mutations such as EGFR exon 19 deletions or the exon 21 L858R mutation initially show satisfactory responsiveness to EGFR-TKI treatment (1,2), acquired resistance to EGFR-TKIs occurs in most cases (6). Half of all resistance to EGFR-TKIs is caused by an acquired T790M mutation in exon 20 of the EGFR gene (7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

Presence of the minor EGFR T790M mutation is associated with drug-sensitive EGFR mutations in lung adenocarcinoma patients

et al. 2014

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Abstract. The T790M mutation in the epidermal growth factor receptor (EGFR) gene is known to be associated with the acquired resistance of lung adenocarcinoma patients to EGFRtyrosine kinase inhibitors (EGFR-TKIs). The minor T790M mutant allele is occasionally detected in EGFR-TKI-naive tumor samples, yet findings concerning the clinical impact of the minor T790M mutation vary among previous studies. In the present study, we assessed the clinical impact of the minor T790M mutation using a novel, highly sensitive assay combining high-resolution melting (HRM), mutant-enriched PCR and co-amplification at a lower denaturation temperature (COLD)-PCR. We determined the T790M mutational status in 146 surgically resected lung adenocarcinomas without a history of EGFR-TKI treatment using mutant-enriched COLD-HRM (MEC-HRM) and standard HRM assays. The sensitivities of the MEC-HRM and standard HRM assays for the detection of T790M-mutant alleles among wild-type alleles were 0.01 and 10%, respectively. Although the T790M mutation was not detected using a standard HRM assay, we identified 19 (13%) T790M mutations using the MEC-HRM assay and defined these 19 mutations as minor T790M mutations. The proportion of T790M alleles was <0.1% in 17 (84%) of the 19 samples. Multivariate analyses revealed that a minor T790M mutation was significantly associated with the presence of EGFR exon 19 deletions or the L858R mutation (both of which are drug-sensitive EGFR mutations) (P=0.04). In conclusion, the minor EGFR T790M mutations were present in 13% of EGFR-TKI-naive surgically resected lung adenocarcinomas and were associated with drug-sensitive EGFR mutations.

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“…Thus, EGFR downstream signal transduction pathways are blocked, inducing cell cycle arrest and inhibition of other activities (Figure 2). 14,15,16 Researchers have shown that mutations in the EGFR tyrosine kinase domain, which is responsible for activating antiapoptotic pathways, tend to confer increased sensitivity to gefitinib 17,18. Other studies have indicated that patients harboring EGFR mutations in exon 19 (deletion) or exon 21 (L858R) are sensitive to gefitinib 19,20.…”

Section: Pharmacology Mode Of Action and Pharmacokinetics Of Gefitinibmentioning

confidence: 99%

Critical appraisal of the role of gefitinib in the management of locally advanced or metastatic non-small cell lung cancer

Yuan¹,

Li²,

Chen³

et al. 2014

OTT

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Past studies have demonstrated that epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors can significantly improve clinical outcomes in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) and sensitive EGFR gene mutations. Gefitinib (Iressa®), the first oral EGFR tyrosine kinase inhibitor, has been shown to be more effective and better tolerated than chemotherapy either in first-line or second-line treatment for patients with advanced NSCLC harboring sensitive EGFR mutations. Conversely, among patients with wild-type EGFR, gefitinib is inferior to standard chemotherapy in both the first-line and second-line settings. Further, gefitinib is effective in patients with brain metastases because of its low molecular weight and excellent penetration of the blood–brain barrier. In this review, we summarize the current data from clinical trials with gefitinib and appraise its role in the management of locally advanced or metastatic NSCLC.

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Review of the Treatment of Non-Small Cell Lung Cancer with Gefitinib

Cited by 34 publications

References 98 publications

Inhibition of non-small cell lung cancer (NSCLC) growth by a novel small molecular inhibitor of EGFR

Inhibition of non-small cell lung cancer (NSCLC) growth by a novel small molecular inhibitor of EGFR

Presence of the minor EGFR T790M mutation is associated with drug-sensitive EGFR mutations in lung adenocarcinoma patients

Critical appraisal of the role of gefitinib in the management of locally advanced or metastatic non-small cell lung cancer

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