Epidermal Growth Factor Receptor Mutations in Plasma DNA Samples Predict Tumor Response in Chinese Patients With Stages IIIB to IV Non–Small-Cell Lung Cancer

Bai, Hua; Li, Mao; Wang, Hang Shu; Zhao, Jun; Yang, Lu; An, T.; Wang, Xin; Duan, Chun Jian; Wu, Na; Guo, Zhi Qing; Liu, Yi Xu; Liu, Hong Ning; Wang, Ye Yu; Wang, Jie

doi:10.1200/jco.2008.17.3930

Cited by 243 publications

(269 citation statements)

References 20 publications

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“…Nevertheless, it's difficult to obtain tumor tissues from patients with advanced or recurrent NSCLC. Although several studies have focused on exploring the potential possibility of detecting EGFR mutation in circulating tumor DNA from plasma or other non-tissue samples, the concordance rate of EGFR mutation status between these samples and matched tumor tissue were not stable, varying from 59.1% to 92% [33][34][35][36]. It seems that assessing EGFR mutation status using blood sample is not absolutely accurate.…”

Section: Discussionmentioning

confidence: 97%

Individualized treatment of NSCLC: From research to clinical practice

Zd²,

Lm³

et al. 2013

neo

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The exact clinical significance of EGFR mutation status in NSCLC at the time of initial diagnosis remains disputable. The gene expression module in NSCLC for chemotherapy outcome prediction needs to be developed. We analyzed 56 patients with NSCLC received chemotherapy either with (n=20) or without EGFR-TKIs (n=36) between 2008 and 2012 in China. EGFR mutation test and gene expression profiling were performed in samples obtained before medication treatment by liquidchip platform. Significant association (P = 0.028) was seen between EGFR mutation status before first-line chemotherapy and EGFR-TKIs treatment outcomes, which even can be found from the status before second-or third-line treatment. A 14-gene expression profiling had been studied. Patients with low mRNA expression of ERCC1 or TYMS preferred higher DCR to cisplatin and pemetrexed than those with high expression (P = 0.39 and P = 0.11). Highly co-expression of TUBB3 and STMN1 gene has associated with the resistance to antimicrotubule drugs (P = 0.03). Our data suggest the EGFR mutations status, even at the time of initial diagnosis, is predictive of outcomes of TKIs treatment after chemotherapy. The mRNA expression profiling investigated in this study has a predictive value in NSCLC treatment, but further research with expanded samples is still required.

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Section: Discussionmentioning

confidence: 97%

Individualized treatment of NSCLC: From research to clinical practice

Zd²,

Lm³

et al. 2013

neo

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“…In the study of Bay et al, 109 consisting of 77 patients with primary tumor EGFR mutations, 63 reported identical alterations in the matched plasma. Moreover, 7% of patients with plasma mutations had no detectable alterations in the corresponding primary tumors and, similarly, 6% of patients with tumor mutations had no detectable EGFR alterations in the corresponding plasma.…”

Section: Biological Samples Suitable For Molecular Characterizationmentioning

confidence: 98%

“…105 Subsequent studies have attempted to confirm these results in larger case series. [106][107][108][109][110][111][112] Indeed, using a range of different methodologies, serum/plasma EGFR mutations have been reported in over 70% of patients in which the tumor tissue showed the same mutation (Table 2).…”

Section: Biological Samples Suitable For Molecular Characterizationmentioning

confidence: 99%

Predictive molecular markers for EGFR-TKI in non-small cell lung cancer patients: new insights and critical aspects

Ulivi

Calistri

Zoli

et al. 2010

J Nucleic Acids Invest

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In recent years, a number of novel agents have been investigated that target specific molecular pathways in non-small cell lung cancer (NSCLC). A great deal of effort has been focused on identifying specific markers that predict treatment response, given that a tailored approach would maximize both the therapeutic index and the cost-effectiveness. The epidermal growth factor receptor (EGFR) pathway has emerged as a key regulator of cancer cell proliferation and invasion, and several specific EGFR inhibitors have been examined. Gefitinib and erlotinib are selective EGFR tyrosine kinase inhibitors (EGFR-TKIs), demonstrating good results in selected cases both in terms of objective response rate and of overall survival. At present, EGFR gene mutations are the best positive predictive factors for TKI therapy, and a number of other potential biomarkers are being investigated as additional positive or negative predictors of response. The correct selection of patients that could benefit from these innovative therapies, based on an accurate molecular characterization, is mandatory to provide the best clinical management. Currently, the main factor limiting the characterization of metastatic NSCLC patients is the small quantity of tumor cells available for molecular analysis. In this paper we provide an overview of the most important molecular predictive markers for EGFR-TKIs therapy in NSCLC patients, and focus attention on biological samples suitable for analysis and alternative sampling approaches such as plasma-or serum-derived DNA.

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“…In lung SqCCs, EGFR mutations are considered as a rare molecular event; they are reported in less than 5% of Caucasians and are reported at seemingly higher rates in Asians, ranging from 0% to 20.3% (10,14,(24)(25)(26)(27)(28)(29)(30). In our study, the frequency of EGFR mutation in advanced lung SqCC patients was 9.6%.…”

Section: Discussionmentioning

confidence: 99%

Activation of the BMP-BMPR pathway conferred resistance to EGFR-TKIs in lung squamous cell carcinoma patients with EGFR mutations

Wang

Shen

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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The empirical criteria for defining a clinical subtype of lung cancer are gradually transiting from histopathology to genetic variations in driver genes. Targeting these driver mutations, such as sensitizing epidermal growth factor receptor (EGFR) mutations, has dramatically improved the prognosis of advanced non-small cell lung cancer (NSCLC). However, the clinical benefit of molecularly targeted therapy on NSCLC appears to be different between lung adenocarcinomas and squamous cell carcinomas (SqCCs). We report here that the resistance of lung SqCC harboring EGFR mutations to EGFR tyrosine kinase inhibitors (EGFR-TKIs) was due to the activation of BMP-BMPR-Smad1/5-p70S6K. The combined treatment of these tumor cells with EGFR-TKI, together with inhibitors specific to BMPR or downstream mTOR, effectively reversed the resistance to EGFR-TKI. Moreover, blocking the whole PI3K-AKTmTOR pathway with the PI3K/mTOR dual inhibitor BEZ235 also showed efficacy in treating this subtype of lung SqCC. This study details the empirical basis for a feasible clinical solution for squamous cell carcinomas with EGFR mutations.epidermal growth factor receptor tyrosine kinase inhibitor | lung squamous cell carcinoma | bone morphogenetic proteins | drug resistance

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Epidermal Growth Factor Receptor Mutations in Plasma DNA Samples Predict Tumor Response in Chinese Patients With Stages IIIB to IV Non–Small-Cell Lung Cancer

Abstract: EGFR mutations can be reliably detected in plasma DNA of patients with stages IIIB to IV NSCLC and can be used as a biomarker to predict tumor response to TKIs.

Cited by 243 publications

References 20 publications

Individualized treatment of NSCLC: From research to clinical practice

Individualized treatment of NSCLC: From research to clinical practice

Predictive molecular markers for EGFR-TKI in non-small cell lung cancer patients: new insights and critical aspects

Activation of the BMP-BMPR pathway conferred resistance to EGFR-TKIs in lung squamous cell carcinoma patients with EGFR mutations

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