Circulating HER2 extracellular domain (HER2 ECD) levels were proposed as a surrogate for HER2 tissue expression to monitor breast cancer patients for early relapse or responses to standard or HER2-targeted therapies, such as the monoclonal antibody (mAb) trastuzumab. Currently, available commercial ELISA assays for HER2 ECD rely on antibodies recognizing undisclosed or unknown epitopes. In this work, two ELISA assays employing MGR2 and MGR3 epitope-specific mAbs for HER2 ECD were developed and validated, showing good assay precision and linearity of the dose-response signal within the dynamic range of 0.19-12.50 ng mL and detection limits of 0.76 and 0.75 ng mL for the MGR2 and MGR3 assays, respectively. The developed assay showed a good agreement with two widely used commercial kits for HER2 ECD quantification in serum samples from breast cancer patients. A complete characterization of mAb-HER2 ECD interaction was performed by means of surface plasmon resonance using trastuzumab as control for both epitope mapping and kinetics analysis. The epitopes recognized by the two mAbs showed no overlap with trastuzumab, which was confirmed by trastuzumab interference analysis in serum samples. The method showed to be a practical approach to determine HER2 ECD with a high degree of sensitivity, reliability and recovery in samples containing mAbs-based therapies.
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http://dx.doi.org/10.1038/s41598-020-59630-y | DOI Listing |
Anal Chem
December 2024
Higher Educational Key Laboratory for Nano Biomedical Technology of Fujian Province, Department of Pharmaceutical Analysis, Faculty of Pharmacy, Fujian Medical University, Fuzhou 350122, China.
The extracellular domain (ECD) of human epidermal growth factor receptor 2 (HER2) serves as a promising biomarker for the early diagnosis and treatment of breast cancer (BC). However, due to the heterogeneity of tumors, assessing HER2 status through a core needle biopsy presents significant challenges. In this study, we propose a facile and high-performance electrochemiluminescence immunoassay (ECLIA) platform utilizing a herceptin-encapsulated gold nanoclusters (HER-AuNCs)/(diisopropylamino)ethanol (DIPEA-OH) ECL system for the clinical evaluation of HER2 ECD in BC patients.
View Article and Find Full Text PDFLancet Reg Health Eur
February 2025
Karolinska Institutet, Oncology/Pathology Department, Stockholm, Sweden.
Background: It is unclear whether some patients with high-risk breast cancer do not warrant adjuvant dose-dense chemotherapy due to small expected absolute benefit.
Methods: The phase 3 PANTHER trial (NCT00798070) compared adjuvant sequential epirubicin/cyclophosphamide (EC) and docetaxel (D) administered in either tailored dose-dense (tDD EC/D) or standard interval schedule (FEC/D) to patients with high-risk resected early breast cancer (n = 2003). We compared outcomes across key subgroups of interest, evaluated the performance of the online prognostication and treatment benefit estimation tool PREDICT and conducted a subpopulation treatment effect pattern plot (STEPP) analysis.
Nat Chem Biol
October 2024
Laura and Isaac Perlmutter Cancer Center, New York University Langone Health, New York, NY, USA.
Oncogenic mutations in the extracellular domain (ECD) of cell-surface receptors could serve as tumor-specific antigens that are accessible to antibody therapeutics. Such mutations have been identified in receptor tyrosine kinases including HER2. However, it is challenging to selectively target a point mutant, while sparing the wild-type protein.
View Article and Find Full Text PDFCells
August 2024
Department of Medical Genetics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2H7, Canada.
Overexpression of HER2 occurs in 25% of breast cancer. Targeting HER2 has proven to be an effective therapeutic strategy for HER2-positive breast cancer. While trastuzumab is the most commonly used HER2 targeting agent, which has significantly improved outcomes, the overall response rate is low.
View Article and Find Full Text PDFClin Breast Cancer
December 2024
Department of Medical Oncology, The University of North Carolina at Chapel Hill, Chapel Hill, NC; Lineberger Comprehensive Cancer Center, Chapel Hill, NC.
Background: Alpelisib is an oral α-specific class I PI3K inhibitor approved in combination with fulvestrant for the treatment of PIK3CA-mutated hormone receptor-positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) metastatic breast cancer. The tolerability of this drug with the oral chemotherapy capecitabine is unknown.
Patients And Methods: This phase I trial evaluated the dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of alpelisib (250 mg or 300 mg daily for 3-weeks) with capecitabine (1000 mg/m twice daily for 2-weeks followed by a 1-week rest period) in patients with metastatic HER2-negative breast cancer, regardless of PIK3CA mutation status.
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