Challenges in the clinical utility of the serum test for HER2 ECD

Lam, Lian; McAndrew, Nicholas P.; Yee, Marla; Fu, Ting; Tchou, Julia; Zhang, Hongtao

doi:10.1016/j.bbcan.2012.03.012

Cited by 56 publications

(84 citation statements)

References 76 publications

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Section: Introductionmentioning

confidence: 99%

“…The HER2 gene expresses a transmembrane protein that is overexpressed in approximately 15-30% of breast cancers [8][9][10][11][12]. Breast cancers associated with HER2 over-expression have an accelerated growth and recurrence rate, and are associated with decreased overall patient survival [12]. HER2 is a 185 kDa protein and has three domains: an extracellular domain (ECD), a transmembrane region, and an intracellular tyrosine kinase domain [10][11][12].…”

Section: Introductionmentioning

confidence: 99%

“…Breast cancers associated with HER2 over-expression have an accelerated growth and recurrence rate, and are associated with decreased overall patient survival [12]. HER2 is a 185 kDa protein and has three domains: an extracellular domain (ECD), a transmembrane region, and an intracellular tyrosine kinase domain [10][11][12]. As many other membrane-anchored proteins, HER2 can release its ECD into the circulation through a proteolytic mechanism [10].…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, the IHC and FISH methods only provide semi-qualitative results, separating patients into HER2-positive and HER2-negative groups [13], whereas a serum test provides quantitative results. An elevated HER2 ECD serum level, which is more frequently observed in metastatic breast cancer, is defined as Z15 ng/mL and was detected by a Food and Drug Administration (FDA)-approved enzyme-linked immunosorbent assay (ELISA) in up to 45% of metastasized breast cancer patients [8,12]. Although the currently approved cut-off value is 15 ng/mL, moderate increase (50 ng/mL) has also been described in the absence of cancer [10] and other cut-off values have been suggested [12].…”

Section: Introductionmentioning

confidence: 99%

“…An elevated HER2 ECD serum level, which is more frequently observed in metastatic breast cancer, is defined as Z15 ng/mL and was detected by a Food and Drug Administration (FDA)-approved enzyme-linked immunosorbent assay (ELISA) in up to 45% of metastasized breast cancer patients [8,12]. Although the currently approved cut-off value is 15 ng/mL, moderate increase (50 ng/mL) has also been described in the absence of cancer [10] and other cut-off values have been suggested [12]. The major advantage of a HER2 ECD serum test, besides its diagnostic value, is the possibility of patient follow-up and the monitoring of (metastatic) breast cancer, which is of critical importance in the choice of the HER2-targeted therapy.…”

Section: Introductionmentioning

confidence: 99%

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Electrochemical immunosensor for the analysis of the breast cancer biomarker HER2 ECD

Marques

Subramanian

Nouws

et al. 2014

Talanta

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a b s t r a c tHuman epidermal growth factor receptor 2 (HER2) is a breast cancer biomarker that plays a major role in promoting breast cancer cell proliferation and malignant growth. The extracellular domain (ECD) of HER2 can be shed into the blood stream and its concentration is measurable in the serum fraction of blood. In this work an electrochemical immunosensor for the analysis of HER2 ECD in human serum samples was developed. To achieve this goal a screen-printed carbon electrode, modified with gold nanoparticles, was used as transducer surface. A sandwich immunoassay, using two monoclonal antibodies, was employed and the detection of the antibody-antigen interaction was performed through the analysis of an enzymatic reaction product by linear sweep voltammetry. Using the optimized experimental conditions the calibration curve (i p vs. log[HER2 ECD]) was established between 15 and 100 ng/mL and a limit of detection (LOD) of 4.4 ng/mL was achieved. These results indicate that the developed immunosensor could be a promising tool in breast cancer diagnostics, patient follow-up and monitoring of metastatic breast cancer since it allows quantification in a useful concentration range and has an LOD below the established cut-off value (15 ng/mL).

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Electrochemical immunosensor for the analysis of the breast cancer biomarker HER2 ECD

Marques

Subramanian

Nouws

et al. 2014

Talanta

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The Evolving Landscape of HER2 Targeting in Breast Cancer

2015

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The development of human epidermal growth factor receptor 2 (HER2)-targeting agents for the treatment of HER2-amplified breast cancer has dramatically improved outcomes for patients with this disease. The value of HER2 as a therapeutic target encompasses 2 entirely different mechanistic dimensions. The first approach exploits the fact that HER2 is clearly a disease-driving oncogene to deliver HER2 kinase inhibitors, apparently a highly rational approach to the treatment of HER2-amplified cancers. However, the functionally relevant HER2-HER3 complex has proven much more difficult to inhibit than had been anticipated, and because of its modest efficacy, the HER2 inhibitor lapatinib is currently used predominantly in combinations and in very advanced stages of disease. The second approach exploits the massive cell surface expression of HER2 and delivers of a variety of cytotoxic or immunologic effectors with great selectivity to these cancer cells. This approach has proven transformative, with 3 such drugs introduced into practice to date. The HER2-specific antibody trastuzumab, in combination with chemotherapy, has shown substantial effect in the management of HER2-amplifed breast cancer at all stages of disease and lines of therapy-and the addition of the second HER2 antibody pertuzumab substantially increases the magnitude of this effect in all of the contexts tested thus far. While the immunologic effectors stimulated by these naked HER2 antibodies provide only modest activity as monotherapy, the toxin-carrying antibody trastuzumab-emtansine provides substantial single-agent activity and is being developed for both early- and late-stage disease. The diverse mechanistic landscape afforded by the target HER2 has proven to be fertile ground for drug development, but it has also created complexity and misconception in understanding these agents' modes of action, undermining the development of clinically useful predictive biomarkers. This accounts for the failure of signaling-based biomarkers to predict clinical trastuzumab resistance and shifted the focus to markers of immunologic activity with greater success. The evolving world of HER2 targeting is reviewed herein.

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Development of Electrochemical Immunosensors towards Point‐of‐care Cancer Diagnostics: Clinically Relevant Studies

Laocharoensuk

2016

Electroanalysis

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Development of electrochemical biosensors towards cancer biomarker detection has been in the spot light for several decades. Electrochemical detection holds great promise for clinical applications because it offers several advantages including sensitive, fast, simple and low‐cost. In addition, multiplexing capability for simultaneous detection of multiple biomarkers is feasible. Unfortunately, transition of biosensors from laboratories to the market is challenging. This review intends to summarize recent advances in the development of electrochemical immunosensors for the next generation cancer diagnostic devices. Clinically relevant details of cancer biomarkers such as threshold value and their diagnosis/prognosis application will be given in conjunction with the electrochemical detection platforms that have been validated using clinical samples. Finally, the critical aspects that require great attention in order to fulfill the criteria of biomedical diagnostics will be covered.

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Challenges in the clinical utility of the serum test for HER2 ECD

Cited by 56 publications

References 76 publications

Electrochemical immunosensor for the analysis of the breast cancer biomarker HER2 ECD

Electrochemical immunosensor for the analysis of the breast cancer biomarker HER2 ECD

The Evolving Landscape of HER2 Targeting in Breast Cancer

Development of Electrochemical Immunosensors towards Point‐of‐care Cancer Diagnostics: Clinically Relevant Studies

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