EGFR and HER2 Gene Copy Number and Response to First-Line Chemotherapy in Patients with Advanced Non-small Cell Lung Cancer (NSCLC)

Cappuzzo, Federico; Ligorio, C.; Toschi, Luca; Rossi, Elisa; Trisolini, Rocco; Paioli, Daniela; Magrini, Elisabetta; Finocchiaro, Giovanna; Bartolini, Stefania; Cancellieri, Alessandra; Hirsch, Fred R.; Crinò, Lucio; Varella‐Garcia, Marileila

doi:10.1097/01.jto.0000268676.79872.9b

Cited by 78 publications

(60 citation statements)

References 43 publications

(59 reference statements)

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“…[30][31][32] Preoperative evaluations include examination of one of the following specimens: bronchial brushings, bronchial washings, fine-needle aspiration (FNA) biopsy, core needle biopsy, endobronchial biopsy, and transbronchial biopsy. The mediastinal lymph nodes are also sampled to assess the staging and therapeutic options.…”

Section: Pathologic Evaluation Of Lung Cancermentioning

confidence: 99%

Non–Small Cell Lung Cancer

Ettinger

Akerley

Bepler

et al. 2010

J Natl Compr Canc Netw

602

371

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Section: Pathologic Evaluation Of Lung Cancermentioning

confidence: 99%

Non–Small Cell Lung Cancer

Ettinger

Akerley

Bepler

et al. 2010

J Natl Compr Canc Netw

602

371

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“…Surprisingly, overexpression is associated with lower stage and grade of tumor [182]. Interestingly, there is an association of HER2/neu overexpression with NSCLC resistance to chemotherapy [183][184][185][186][187][188][189][190][191], which may account for the fact that HER2/neu overexpression is associated with a poor prognosis [35,[160][161][162][163][164][165][166][167][168][169][170][171][172][173] despite the association of HER2/neu overexpression with lower stage and grade. There is evidence for cooperativity and co-expression of HER1/EGFR [192], potentially associated with poorer prognosis [161,169,193], and there is data to support overexpression of HER2/neu as a mechanism for resistance to antibody inhibition of HER1/EGFR [194].…”

Section: Lungmentioning

confidence: 99%

HER2/neu: an increasingly important therapeutic target. Part 2: Distribution of HER2/neu overexpression and gene amplification by organ, tumor site and histology

Nelson¹

2014

Clinical Investigation

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No biological molecule in the field of oncology has been more extensively or more successfully targeted for therapeutic intent than the product of the c-erbB2 gene, HER2/neu. This is the second of a comprehensive three-part review of the foundation for and therapeutic targeting of HER2/neu. The distribution of HER2/neu overexpression and/or gene amplification by individual tumor sites and histologies will be comprehensively surveyed and described. This provides a bridge between the primarily basic science focused Part I, and the survey of clinical applications to follow in Part III. In combination, this comprehensive survey will identify opportunities and promising areas for future evaluation of HER2/neu-targeted therapies, highlighting the importance of HER2/neu as an increasingly important therapeutic target.

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“…Of the EGFR family of proteins, the expression of HER3 and/or HER2 has been shown to affect responses to EGFR-targeted drugs both in vitro and in vivo (13)(14)(15). A secondary EGFR mutation, T790M, has been identified that emerged after EGFR-TKI treatment (16)(17)(18), whereas K-ras mutations have been reported to be linked to primary resistance to EGFR-TKIs (19,20).…”

Section: Introductionmentioning

confidence: 99%

Loss of PTEN Expression by Blocking Nuclear Translocation of EGR1 in Gefitinib-Resistant Lung Cancer Cells Harboring Epidermal Growth Factor Receptor–Activating Mutations

et al. 2010

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Gefitinib (Iressa) and erlotinib (Tarceva), which target the epidermal growth factor receptor (EGFR), are approved for treatment of patients with advanced non-small cell lung cancer (NSCLC). Patients whose tumors harbor mutations in the EGFR gene, including delE746-A750 in exon 19 and L858R in exon 21, may benefit in particular from gefitinib treatment. However, acquired resistance to gefitinib has been a serious clinical problem, and further optimization is needed for application of EGFR-targeted drugs in lung cancer patients. In this study, we established gefitinib-resistant NSCLC cells from PC-9 cell line, which harbors the delE746-A750 mutation, by exposing the cell line to gefitinib for over 7 months. Gefitinib-resistant PC-9/GEFs cell lines showed a marked downregulation of PTEN expression and increased Akt phosphorylation. In revertant, gefitinibsensitive clones (PC-9/Rev) derived from PC-9/GEF1-1 and PC-9/GEF2-1, PTEN expression, as well as sensitivity to gefitinib and erlotinib, was restored. Knockdown of PTEN expression using small interfering RNA specific for PTEN in PC-9 cells resulted in drug resistance to gefitinib and erlotinib. Nuclear translocation of the EGR1 transcription factor, which regulates PTEN expression, was shown to be suppressed in resistant clones and restored in their revertant clones. Reduced PTEN expression was also seen in tumor samples from a patient with gefitinib-refractory NSCLC. This study thus strongly suggests that loss of PTEN expression contributes to gefitinib and erlotinib resistance in NSCLC. Our findings reinforce the therapeutic importance of PTEN expression in the treatment of NSCLC with EGFR-targeted drugs. Cancer Res; 70(21); 8715-25. ©2010 AACR.

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EGFR and HER2 Gene Copy Number and Response to First-Line Chemotherapy in Patients with Advanced Non-small Cell Lung Cancer (NSCLC)

Abstract: This study suggested that EGFR expression and gene copy number, HER2 gene copy number, and P-Akt expression are not associated with response to first-line chemotherapy in NSCLC. Prospective phase III trials should compare standard chemotherapy with a TKI in selected NSCLC.

Cited by 78 publications

References 43 publications

Non–Small Cell Lung Cancer

Non–Small Cell Lung Cancer

HER2/neu: an increasingly important therapeutic target. Part 2: Distribution of HER2/neu overexpression and gene amplification by organ, tumor site and histology

Loss of PTEN Expression by Blocking Nuclear Translocation of EGR1 in Gefitinib-Resistant Lung Cancer Cells Harboring Epidermal Growth Factor Receptor–Activating Mutations

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