The effect of HER2 expression on cisplatin-based chemotherapy in advanced non-small cell lung cancer patients

Çalıkuşu, Züleyha; Yıldırım, Yeşim; Akçalı, Zafer; Sakallı, Hakan; Bal, Nebil; Ünal, İ̇lker; Ozyilkan, Ozgür

doi:10.1186/1756-9966-28-97

Cited by 24 publications

(13 citation statements)

References 25 publications

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“…35 However, in these studies, as well as in others, not all these features were confirmed to be associated with HER2 overexpression and in some instances were rejected. 27,30,31,[37][38][39][40] In addition to IHC assays, other authors have attempted to evaluate HER2 expression with other methodologies, such as real-time polymerase chain reaction assay. Brabender et al, 41 using a cutoff value of 1.8 ratio between lung tumors and normal tissues, reported that high HER2 mRNA levels were associated with an unfavorable prognosis and that the impact of HER2/EGFR co-expression on survival was additive (p = 0.176).…”

Section: Her2 Overexpression In Nsclcmentioning

confidence: 99%

NSCLC and HER2: Between Lights and Shadows

Ricciardi

Russo

Franchina

et al. 2014

Journal of Thoracic Oncology

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The therapeutic landscape of non-small-cell lung cancer (NSCLC) has dramatically changed in the last few years with the introduction of molecularly targeted agents, leading to unprecedented results in lung tumors with a paradigmatic shift from a "one size fits all" approach to an histologic and molecular-based approach. The discovery of epidermal growth factor receptor (EGFR) mutations in NSCLC in 2004 and the marked response to the EGFR tyrosine kinase inhibitor gefitinib, in a small subset of patients harboring these genetic abnormalities, stimulated the study of other kinase mutants involvement in NSCLC. The incredible story of ALK rearranged tumors, with the rapid Food and Drug Administration approval of Crizotinib after only 4 years from the discovery of EML4-ALK translocation in NSCLC, has profoundly influenced the concept of drug development in NSCLC, paving the way to a novel series of molecularly selected studies with specific inhibitors. The identification of these oncogenic drivers has dramatically changed the genetic landscape of NSCLC moving away from the old concept of a large indistinct histological entity to a combination of rare clinically relevant molecular subsets. Recently, a renewed interest has been emerging on the human epidermal growth factor-2 (HER2) pathway. Genetic aberrations of this signaling pathway have been reported over time to be associated in NSCLC with different sensitivity to the EGFR tyrosine kinase inhibitors, to have a possible prognostic role and more recently HER2 amplification has been emerged as a possible mechanism in EGFR-mutated tumors of acquired resistance to the EGFR tyrosine kinase inhibitors. In addition, dysregulation of the HER2 pathway, in particular HER2 mutations (mostly, in-frame exon 20 insertions), may represent a possible novel therapeutic target in NSCLC, paving the way for a new generation of targeted agents in NSCLC. Since anecdotal case reports of clinical activity of anti-HER2 agents in NSCLC patients with HER2 mutations, several targeted agents have been evaluated in HER2-mutated patients, generating a growing interest upon this oncogenic driver, leading to the design of molecularly selected trials with anti-HER2 compounds and the rediscover of hastily thrown out drugs, such as neratinib. The aim of this article is to provide an overview of the role of HER2 dysregulation in NSCLCs, trying to throw a light not only on the strengths but also the weaknesses of the studies conducted so far. It is a long way to the clinical implementation of these biomarkers and probably the increasing use of next generation sequencing techniques, the creation of large multi-institutional molecular testing platforms and the design of rationally based trials can get closer personalized medicine in NSCLC.

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Section: Her2 Overexpression In Nsclcmentioning

confidence: 99%

NSCLC and HER2: Between Lights and Shadows

Ricciardi

Russo

Franchina

et al. 2014

Journal of Thoracic Oncology

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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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“…The impact of expression could be analysed in process of determination of type of NSCLC treatment. It is known that in some cases, patients overexpressing HER2 are resistant to certain chemotherapeutic regimens, while the same patients have been proposed for therapy with monoclonal antibody-trastuzumab [23,24]. Due to small numto HER3 immunoreactivity of the tumors we found that: 11 (29.7 %) cancers were negative; 15 (40.5 %) shown low expression; 9 (24.3 %) had moderate expression and strong immunoreactivity in 2 (5.4 %) cases (Fig.…”

Section: Discussionmentioning

confidence: 99%

Impact of HER2 codon 655 polymorphism and expression of HER2 and HER3 in non small cell lung cancer patients

Ananiev

Aleksandrova

Skerleva

et al. 2015

Wien Med Wochenschr

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The aim of the study was to assess the expression and significance of HER2 and HER3, and Ile/Val single nucleotide polymorphism (SNP) of HER2 in lung cancer patients. Thirty seven cases of lung cancer were investigated immunohistochemically for HER2 and HER3 expression. PCR followed by restriction fragment length polymorphism (RFLP) was used to analyze the presence of HER-2 SNP at codon 655 in 20 samples. The results were compared with clinical and pathological parameters of investigated patients.We found that 100% of the cases were negative for HER2, 29.7% were with moderate or strong HER3 expression and 70.3% of the tumors-without or with low expression for HER3. Lymph node metastasis were found in 40% of HER3 positive cases (χ(2) = 4.752; p = 0.029). Moderately-differentiated tumors do not express neither of investigated markers (χ(2) = 6.719; p = 0.035). HER2 RFLP-PCR analysis showed genotype AG in five patients (25%) and the rest of 15 cases (75%) had АА (Ile/Ile) genotype. Patients with metastasis had genotype АА (Ile/Ile) in 80% and genotype AG (Ile/Val) in 20% (χ(2) = 2.857; p = 0.091).Our results indicate that SNP in HER2 codon 655 and investigation of HER2 and HER3 expression could be helpful to outline the prognosis for patients with lung adenocarcinoma.

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The effect of HER2 expression on cisplatin-based chemotherapy in advanced non-small cell lung cancer patients

Abstract: Introduction: The prognostic value of HER2 expression in patients with advanced non-small cell lung cancer remains controversial. The relationship between HER2 expression, and platinum resistance and patient survival, was investigated.

Cited by 24 publications

References 25 publications

NSCLC and HER2: Between Lights and Shadows

NSCLC and HER2: Between Lights and Shadows

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

Impact of HER2 codon 655 polymorphism and expression of HER2 and HER3 in non small cell lung cancer patients

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