scholarly journals HER2 Heterogeneity in Personalized Therapy of Gastro-Oesophageal Malignancies: An Overview by Different Methodologies

2020 ◽  
Vol 10 (1) ◽  
pp. 10
Author(s):  
Antonio Ieni ◽  
Roberta Cardia ◽  
Cristina Pizzimenti ◽  
Pio Zeppa ◽  
Giovanni Tuccari
Keyword(s):  
Current Knowledge ◽  
Growth Factor Receptor ◽  
Resistance Mechanisms ◽  
Her2 Status ◽  
Significant Heterogeneity ◽  
Her2 Expression ◽  
Detection Systems ◽  
Therapeutic Choice ◽  
Epidermal Growth ◽  
Her2 Heterogeneity

Human epidermal growth factor receptor-2 (HER2)-expression gastro-oesophageal adenocarcinomas (GEA) gained interest as an important target for therapy with trastuzumab. In the current review, we focused the current knowledge on HER2 status in dysplastic and neoplastic gastric conditions, analyzing the methodological procedures to identify HER2 expression/amplification, as well as the proposed scoring recommendations. One of the most relevant questions to evaluate the useful impact of HER2 status on therapeutic choice in GEAs is represented by the significant heterogeneity of HER2 protein and gene expression that may affect the targeted treatment selection. Future development of biotechnology will continue to evolve in order to offer more powerful detection systems for the assessment of HER2 status. Finally, liquid biopsy as well as mutation/amplification of several additional genes may furnish an early detection of secondary HER2 resistance mechanisms in GEAs with a better monitoring of the treatment response.

scholarly journals The Prognostic Impact of HER2 Genetic and Protein Expression in Pancreatic Carcinoma—HER2 Protein and Gene in Pancreatic Cancer

Diagnostics ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 653
Author(s):  
Song-Hee Han ◽  
Ki Hyun Ryu ◽  
Ah-Young Kwon
Keyword(s):  
Protein Expression ◽  
Genetic Heterogeneity ◽  
Growth Factor Receptor ◽  
Ductal Adenocarcinoma ◽  
Prognostic Impact ◽  
Her2 Expression ◽  
Her2 Protein ◽  
Epidermal Growth ◽  
Her2 Heterogeneity

Pancreatic ductal adenocarcinoma (PDAC) is a lethal and clinically heterogeneous disease with a limited benefit from human epidermal growth factor receptor 2 (HER2)-targeted therapy. Recently, some studies have addressed the antitumoral effect of novel anti-HER2 drugs in HER2 low-expressing tumors. However, there have been few studies on the significance of low HER2 expression and genetic heterogeneity in PDAC. Using immunohistochemistry and dual-color silver-enhanced in situ hybridization based on the Trastuzumab for a gastric cancer scoring scheme, we evaluated HER2 protein expression, gene amplification, and genetic heterogeneity in three groups (HER2-neg, HER2-low, HER2-pos) of 55 patients. Among the 55 cases, 41.8% (23/55) showed HER2 expression of any intensity. HER2 amplification independent of HER2 expression was 25.5% (14/55). Patients in both these groups had a shorter overall survival than did patients in the HER2-neg group. HER2 genetic heterogeneity was identified in 37 (70.9%) of the 55 cases, mainly in HER2-neg and HER2-low groups. HER2 genetic heterogeneity significantly correlated with worse survival in the HER2-low and HER2-neg groups of PDAC. These findings support the hypothesis that low-level HER2 expression and heterogeneity have significant clinical implications in PDAC. HER2 heterogeneity might indicate the best strategies of combination therapies to prevent the development of subdominant clones with resistance potential.

scholarly journals Clinical Application of Multiple Reaction Monitoring-Mass Spectrometry to Human Epidermal Growth Factor Receptor 2 Measurements as a Potential Diagnostic Tool for Breast Cancer Therapy

2020 ◽  
Vol 66 (10) ◽  
pp. 1339-1348
Author(s):  
Misol Do ◽  
Hyunsoo Kim ◽  
Injoon Yeo ◽  
Jihyeon Lee ◽  
In Ae Park ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mass Spectrometry ◽  
Multiple Reaction Monitoring ◽  
Growth Factor Receptor ◽  
Specific Protein ◽  
Her2 Status ◽  
Reaction Monitoring ◽  
Her2 Expression ◽  
Expression Levels ◽  
Epidermal Growth

Abstract Background Human epidermal growth factor receptor 2 (HER2) is often overexpressed in breast cancer and correlates with a worse prognosis. Thus, the accurate detection of HER2 is crucial for providing the appropriate measures for patients. However, the current techniques used to detect HER2 status, immunohistochemistry and fluorescence in situ hybridization (FISH), have limitations. Specifically, FISH, which is mandatory for arbitrating 2+ cases, is time-consuming and costly. To address this shortcoming, we established a multiple reaction monitoring-mass spectrometry (MRM-MS) assay that improves on existing methods for differentiating HER2 status. Methods We quantified HER2 expression levels in 210 breast cancer formalin-fixed paraffin-embedded (FFPE) tissue samples by MRM-MS. We aimed to improve the accuracy and precision of HER2 quantification by simplifying the sample preparation through predicting the number of FFPE slides required to ensure an adequate amount of protein and using the expression levels of an epithelial cell-specific protein as a normalization factor when measuring HER2 expression levels. Results To assess the correlation between MRM-MS and IHC/FISH data, HER2 quantitative data from MRM-MS were divided by the expression levels of junctional adhesion molecule A, an epithelial cell-specific protein, prior to statistical analysis. The normalized HER2 amounts distinguished between HER2 2+/FISH-negative and 2+/FISH-positive groups (AUROC = 0.908), which could not be differentiated by IHC. In addition, all HER2 status were discriminated by MRM-MS. Conclusions This MRM-MS assay yields more accurate HER2 expression levels relative to immunohistochemistry and should help to guide clinicians toward the proper treatment for breast cancer patients, based on their HER2 expression.

scholarly journals Epidermal Growth Factor Receptor Inhibitors: A Review of Cutaneous Adverse Events and Management

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
K. Chanprapaph ◽  
V. Vachiramon ◽  
P. Rattanakaemakorn
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Adverse Events ◽  
Current Knowledge ◽  
Growth Factor Receptor ◽  
Skin Toxicity ◽  
Maculopapular Rash ◽  
Postinflammatory Hyperpigmentation ◽  
Epidermal Growth

Epidermal growth factor inhibitors (EGFRI), the first targeted cancer therapy, are currently an essential treatment for many advance-stage epithelial cancers. These agents have the superior ability to target cancers cells and better safety profile compared to conventional chemotherapies. However, cutaneous adverse events are common due to the interference of epidermal growth factor receptor (EGFR) signaling in the skin. Cutaneous toxicities lead to poor compliance, drug cessation, and psychosocial discomfort. This paper summarizes the current knowledge concerning the presentation and management of skin toxicity from EGFRI. The common dermatologic adverse events are papulopustules and xerosis. Less common findings are paronychia, regulatory abnormalities of hair growth, maculopapular rash, mucositis, and postinflammatory hyperpigmentation. Radiation enhances EGFRI rash due to synergistic toxicity. There is a positive correlation between the occurrence and severity of cutaneous adverse effects and tumor response. To date, prophylactic systemic tetracycline and tetracycline class antibiotics have proven to be the most effective treatment regime.

Treatment in EGFR-mutated Non-small Cell Lung Cancer: How to Block the Receptor and overcome Resistance Mechanisms

2017 ◽  
Vol 103 (4) ◽  
pp. 325-337 ◽  
Author(s):  
Claudia Proto ◽  
Giuseppe Lo Russo ◽  
Giulia Corrao ◽  
Monica Ganzinelli ◽  
Francesco Facchinetti ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Growth Factor Receptor ◽  
Resistance Mechanisms ◽  
Small Cell ◽  
Third Generation ◽  
Small Cell Lung ◽  
Epidermal Growth ◽  
Exon 20 ◽  
Egfr Mutated ◽  
Egfr Tkis

In non-small cell lung cancer (NSCLC), the identification of epidermal growth factor receptor (EGFR) mutations and the parallel development of EGFR tyrosine kinase inhibitors (TKIs) have radically changed the therapeutic management strategies. Currently, erlotinib, gefitinib, and afatinib are all approved as standard first-line treatment in EGFR-mutated NSCLC. However, despite the proven efficacy, some EGFR-mutated NSCLCs do not respond to EGFR TKIs, while some patients, after a favorable and prolonged response to EGFR TKIs, inevitably progress within about 10-14 months. Epidermal growth factor receptor-dependent mechanisms, activation of alternative pathways, or phenotypic transformation can cause the resistance to EGFR TKIs. The exon 20 p.Thr790Met point mutation (T790M) is responsible for about 60% of cases of resistance when progression occurs. A third-generation TKI, osimertinib, improved outcome in patients harboring T790M after first- and second-generation TKI treatment. However, resistance develops even after treatment with third-generation drugs. To date, the Cys797Ser (C797S) mutation in exon 20 of EGFR is the most well-known resistance mutation after osimertinib. Fourth-generation TKIs are already under development. Nevertheless, additional information is needed to better understand and effectively overcome resistance. The aim of this review is to report recent advances and future perspectives in the treatment of EGFR-mutated NSCLC, highlighting the resistance mechanisms that underlie disease progression.

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