Challenges in Detection of Serum Oncoprotein: Relevance to Breast Cancer Diagnostics

Justin Lengfeld,1 Hongtao Zhang,2 Steven Stoesz,1 Ramachandran Murali,3 Franklin Pass,1 Mark I Greene,2 Peeyush N Goel,2 Payal Grover2 1Martell Diagnostic Laboratories, Inc., Roseville, MN, 55113, USA; 2Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Penns...

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Autores principales:	Lengfeld J, Zhang H, Stoesz S, Murali R, Pass F, Greene MI, Goel PN, Grover P
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	breast cancer diagnosis elisa detection plasmonics sensitivity Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/a8aa909f915448718fe1205594f3118e
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spelling	oai:doaj.org-article:a8aa909f915448718fe1205594f3118e2021-12-02T19:21:05ZChallenges in Detection of Serum Oncoprotein: Relevance to Breast Cancer Diagnostics1179-1314https://doaj.org/article/a8aa909f915448718fe1205594f3118e2021-10-01T00:00:00Zhttps://www.dovepress.com/challenges-in-detection-of-serum-oncoprotein-relevance-to-breast-cance-peer-reviewed-fulltext-article-BCTThttps://doaj.org/toc/1179-1314Justin Lengfeld,1 Hongtao Zhang,2 Steven Stoesz,1 Ramachandran Murali,3 Franklin Pass,1 Mark I Greene,2 Peeyush N Goel,2 Payal Grover2 1Martell Diagnostic Laboratories, Inc., Roseville, MN, 55113, USA; 2Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA; 3Department of Biomedical Sciences, Research Division of Immunology; Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USACorrespondence: Justin LengfeldMartell Diagnostic Laboratories, Inc., Roseville, MN, 55113, USAEmail JLengfeld@martelldiagnostic.comPayal GroverDepartment of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USAEmail Payalgrover13@gmail.com; pgrover@pennmedicine.upenn.eduAbstract: Breast cancer is a highly prevalent malignancy that shows improved outcomes with earlier diagnosis. Current screening and monitoring methods have improved survival rates, but the limitations of these approaches have led to the investigation of biomarker evaluation to improve early diagnosis and treatment monitoring. The enzyme-linked immunosorbent assay (ELISA) is a specific and robust technique ideally suited for the quantification of protein biomarkers from blood or its constituents. The continued clinical relevancy of this assay format will require overcoming specific technical challenges, including the ultra-sensitive detection of trace biomarkers and the circumventing of potential assay interference due to the expanding use of monoclonal antibody (mAb) therapeutics. Approaches to increasing the sensitivity of ELISA have been numerous and include employing more sensitive substrates, combining ELISA with the polymerase chain reaction (PCR), and incorporating nanoparticles as shuttles for detection antibodies and enzymes. These modifications have resulted in substantial boosts in the ability to detect extremely low levels of protein biomarkers, with some systems reliably detecting antigen at sub-femtomolar concentrations. Extensive utilization of mAb therapies in oncology has presented an additional contemporary challenge for ELISA, particularly when both therapeutic and assay antibodies target the same protein antigen. Resolution of issues such as epitope overlap and steric hindrance requires a rational approach to the design of diagnostic antibodies that takes advantage of modern antibody generation pipelines, epitope binning techniques and computational methods to strategically target biomarker epitopes. This review discusses technical strategies in ELISA implemented to date and their feasibility to address current constraints on sensitivity and problems with interference in the clinical setting. The impact of these recent advancements will depend upon their transformation from research laboratory protocols into facile, reliable detection systems that can ideally be replicated in point-of-care devices to maximize utilization and transform both the diagnostic and therapeutic monitoring landscape.Keywords: breast cancer, diagnosis, ELISA, detection, plasmonics, sensitivityLengfeld JZhang HStoesz SMurali RPass FGreene MIGoel PNGrover PDove Medical Pressarticlebreast cancerdiagnosiselisadetectionplasmonicssensitivityNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENBreast Cancer: Targets and Therapy, Vol Volume 13, Pp 575-593 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	breast cancer diagnosis elisa detection plasmonics sensitivity Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	breast cancer diagnosis elisa detection plasmonics sensitivity Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Lengfeld J Zhang H Stoesz S Murali R Pass F Greene MI Goel PN Grover P Challenges in Detection of Serum Oncoprotein: Relevance to Breast Cancer Diagnostics
description	Justin Lengfeld,1 Hongtao Zhang,2 Steven Stoesz,1 Ramachandran Murali,3 Franklin Pass,1 Mark I Greene,2 Peeyush N Goel,2 Payal Grover2 1Martell Diagnostic Laboratories, Inc., Roseville, MN, 55113, USA; 2Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA; 3Department of Biomedical Sciences, Research Division of Immunology; Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USACorrespondence: Justin LengfeldMartell Diagnostic Laboratories, Inc., Roseville, MN, 55113, USAEmail JLengfeld@martelldiagnostic.comPayal GroverDepartment of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USAEmail Payalgrover13@gmail.com; pgrover@pennmedicine.upenn.eduAbstract: Breast cancer is a highly prevalent malignancy that shows improved outcomes with earlier diagnosis. Current screening and monitoring methods have improved survival rates, but the limitations of these approaches have led to the investigation of biomarker evaluation to improve early diagnosis and treatment monitoring. The enzyme-linked immunosorbent assay (ELISA) is a specific and robust technique ideally suited for the quantification of protein biomarkers from blood or its constituents. The continued clinical relevancy of this assay format will require overcoming specific technical challenges, including the ultra-sensitive detection of trace biomarkers and the circumventing of potential assay interference due to the expanding use of monoclonal antibody (mAb) therapeutics. Approaches to increasing the sensitivity of ELISA have been numerous and include employing more sensitive substrates, combining ELISA with the polymerase chain reaction (PCR), and incorporating nanoparticles as shuttles for detection antibodies and enzymes. These modifications have resulted in substantial boosts in the ability to detect extremely low levels of protein biomarkers, with some systems reliably detecting antigen at sub-femtomolar concentrations. Extensive utilization of mAb therapies in oncology has presented an additional contemporary challenge for ELISA, particularly when both therapeutic and assay antibodies target the same protein antigen. Resolution of issues such as epitope overlap and steric hindrance requires a rational approach to the design of diagnostic antibodies that takes advantage of modern antibody generation pipelines, epitope binning techniques and computational methods to strategically target biomarker epitopes. This review discusses technical strategies in ELISA implemented to date and their feasibility to address current constraints on sensitivity and problems with interference in the clinical setting. The impact of these recent advancements will depend upon their transformation from research laboratory protocols into facile, reliable detection systems that can ideally be replicated in point-of-care devices to maximize utilization and transform both the diagnostic and therapeutic monitoring landscape.Keywords: breast cancer, diagnosis, ELISA, detection, plasmonics, sensitivity
format	article
author	Lengfeld J Zhang H Stoesz S Murali R Pass F Greene MI Goel PN Grover P
author_facet	Lengfeld J Zhang H Stoesz S Murali R Pass F Greene MI Goel PN Grover P
author_sort	Lengfeld J
title	Challenges in Detection of Serum Oncoprotein: Relevance to Breast Cancer Diagnostics
title_short	Challenges in Detection of Serum Oncoprotein: Relevance to Breast Cancer Diagnostics
title_full	Challenges in Detection of Serum Oncoprotein: Relevance to Breast Cancer Diagnostics
title_fullStr	Challenges in Detection of Serum Oncoprotein: Relevance to Breast Cancer Diagnostics
title_full_unstemmed	Challenges in Detection of Serum Oncoprotein: Relevance to Breast Cancer Diagnostics
title_sort	challenges in detection of serum oncoprotein: relevance to breast cancer diagnostics
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/a8aa909f915448718fe1205594f3118e
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Challenges in Detection of Serum Oncoprotein: Relevance to Breast Cancer Diagnostics

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