Efficacy and Survival-associated Factors with Gefitinib Combined with Cisplatin and Gemcitabine for Advanced Non-small Cell Lung Cancer

Fang, Hong; Lin, Rong; Sun, Mingxia; Wang, Qian; Zhao, Yi‐Fang; Yu, Jing-Lin; Tian, Yan; Wang, Xiaoyun

doi:10.7314/apjcp.2014.15.24.10967

Cited by 5 publications

(2 citation statements)

References 12 publications

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“…However, most of these agents are still in clinical trials, and the combination therapy of EGFR-TKIs and platinum-based chemotherapy is the preferred choice for most patients. Previous studies have reported that such combination therapy could improve the overall survival and progression-free survival of patients (15)(16)(17)(18). The synergistic mechanism between EGFR-TKIs and platinum remains unknown, and no biomarkers are currently available to predict the benefit of the combination therapy.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of DNA‑PK by gefitinib causes synergism between gefitinib and cisplatin in NSCLC

Chi

Duan

et al. 2020

Int J Oncol

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Lung cancer has the highest incidence and mortality rates among the malignant tumor types worldwide. Platinum-based chemotherapy is the main treatment for advanced non-small-cell lung cancer (NSCLC), and epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have greatly improved the survival of patients with EGFR-sensitive mutations. However, there is no standard therapy for treating patients who are EGFR-TKI resistant. Combining EGFR-TKIs and platinum-based chemotherapy is the most popular strategy in the clinical practice. However, the synergistic mechanism between EGFR-TKIs and platinum remains unknown. Therefore, the aim of the present study was to determine the synergistic mechanism of gefitinib (an EGFR-TKI) and cisplatin (a main platinum-based drug). MTT assay, apoptosis analysis, tumorsphere formation and an orthotropic xenograft mouse model were used to examine the combination effects of gefitinib and cisplatin on NSCLC. Co-immunoprecipitation and immunofluorescence were used to identify the underlying mechanism. It was found that gefitinib could selectively inhibit EGFR from entering the nucleus, decrease DNA-PK activity and enhance the cytotoxicity of cisplatin on NSCLC. Collectively, the results suggested that inhibition of DNA-dependent protein kinase by gefitinib may be due to the synergistic mechanism between gefitinib and cisplatin. Thus, the present study provides a novel insight into potential biomarkers for the selection of combination therapy of gefitinib and cisplatin.

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Section: Introductionmentioning

confidence: 99%

Inhibition of DNA‑PK by gefitinib causes synergism between gefitinib and cisplatin in NSCLC

Chi

Duan

et al. 2020

Int J Oncol

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“…It has been reported in many literatures that the expression of TS, RRM1, ERCC1, TUBB3 and STMN1 genes is closely associated with the sensitivity of patients with non-small cell lung cancer (NSCLC) to fluorouracil (Fu), gemcitabine, platinum, paclitaxel and navelbine, respectively (Chen et al, 2011;Fang et al, 2014;Gao et al, 2014;Li et al, 2014;Nie et al, 2015). This study applied real time polymerase chain reaction (RT-PCR) to detect the expression of TS, RRM1, ERCC1, TUBB3 and STMN1 genes in the tumor tissues surgically excised from NSCLC patients so as to analyze the expression of above genes in the tissues of patients with lung adenocarcinoma and non-adenocarcinoma and to explore its relationship with the clinical efficacy of postoperative adjuvant chemotherapy, hoping to provide guidance for the postoperative adjuvant chemotherapy and improve the postoperative disease-free survival (DFS) of NSCLC patients.…”

Section: Introductionmentioning

confidence: 99%

Expression of TS, RRM1, ERCC1, TUBB3 and STMN1 Genes in Tissues of Non-small Cell Lung Cancer and its Significance in Guiding Postoperative Adjuvant Chemotherapy

Zou

Du²,

Sui³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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Background: To explore the expression of TS, RRM, ERCC1, TUBB3 and STMN1 genes in the tissues of patients with non-small cell lung cancer (NSCLC) and its significance in guiding the postoperative adjuvant chemotherapy. Materials and Methods: Real time polymerase chain reaction (PCR) was applied to detect the expression of TS, RRM, ERCC1, TUBB3 and STMN1 genes in the tissues of NSCLC patients so as to analyze the relationship between the expression of each gene and the clinical characteristics and to guide the postoperative individualized chemotherapy according to the detection results of NSCLC patients. Results: Expression of TS gene was evidently higher in patients with adenocarcinoma than those with non-adenocarcinoma (P=0.013) and so was the expression of ERCC1 (P=0.003). The expression of TUBB3 gene was obviously higher in NSCLC patients in phases Ⅰ/Ⅱ and Ⅳ than those in phase Ⅲ (P 1 =0.021; P 2 =0.004), and it was also markedly higher in patients without lymph node metastasis than those with (P=0.008). The expression of STMN1 gene was apparently higher in patients in phase Ⅰ/Ⅱ than those in phase Ⅳ (P=0.002). There was no significant difference between the rest gene expression and the clinical characteristics of NSCLC patients (P>0.05). Additionally, the diseasefree survival (DFS) was significantly longer in patients receiving gene detections than those without (P=0.021). Conclusions: The selection of chemotherapeutic protocols based singly on patients' clinical characteristics has certain blindness. However, the detection of tumor-susceptible genes can guide the postoperative adjuvant chemotherapy and prolong the DFS of NSCLC patients.

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Intercalated Chemotherapy and Epidermal Growth Factor Receptor Inhibitors for Patients With Advanced Non–Small-cell Lung Cancer: A Systematic Review and Meta-analysis

Salvia

Rossi

Galetta

et al. 2017

Clinical Lung Cancer

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Efficacy and Survival-associated Factors with Gefitinib Combined with Cisplatin and Gemcitabine for Advanced Non-small Cell Lung Cancer

Cited by 5 publications

References 12 publications

Inhibition of DNA‑PK by gefitinib causes synergism between gefitinib and cisplatin in NSCLC

Inhibition of DNA‑PK by gefitinib causes synergism between gefitinib and cisplatin in NSCLC

Expression of TS, RRM1, ERCC1, TUBB3 and STMN1 Genes in Tissues of Non-small Cell Lung Cancer and its Significance in Guiding Postoperative Adjuvant Chemotherapy

Intercalated Chemotherapy and Epidermal Growth Factor Receptor Inhibitors for Patients With Advanced Non–Small-cell Lung Cancer: A Systematic Review and Meta-analysis

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