Source 1primary paper2025MED
Toolkit/phosphorylated ErbB2 immunohistochemistry
phosphorylated ErbB2 immunohistochemistry
Also known as: IHC with an antibody against phosphorylated ErbB2, phospho-ErbB2 IHC
Taxonomy: Technique Branch / Method. Workflows sit above the mechanism and technique branches rather than replacing them.
Summary
ErbB2 activation, identified by IHC with an antibody against phosphorylated ErbB2
Usefulness & Problems
Why this is useful
This assay uses immunohistochemistry against phosphorylated ErbB2 to identify tumors with activated ErbB2 signaling. In the abstract, it is the method used to detect ErbB2 activation in residual tumors after ASI and in advanced CRPC.; identifying activated ErbB2 signaling in prostate tumor samples; biomarker stratification for tumors that may respond in CRPC
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This assay uses immunohistochemistry against phosphorylated ErbB2 to identify tumors with activated ErbB2 signaling. In the abstract, it is the method used to detect ErbB2 activation in residual tumors after ASI and in advanced CRPC.
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identifying activated ErbB2 signaling in prostate tumor samples
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biomarker stratification for tumors that may respond in CRPC
Problem solved
It addresses the problem that ErbB2 activity can be increased even when ERBB2 is rarely amplified, enabling activity-based detection rather than copy-number-based inference.; detects ErbB2 activation when ERBB2 gene amplification is rare
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It addresses the problem that ErbB2 activity can be increased even when ERBB2 is rarely amplified, enabling activity-based detection rather than copy-number-based inference.
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detects ErbB2 activation when ERBB2 gene amplification is rare
Problem links
detects ErbB2 activation when ERBB2 gene amplification is rare
LiteratureIt addresses the problem that ErbB2 activity can be increased even when ERBB2 is rarely amplified, enabling activity-based detection rather than copy-number-based inference.
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It addresses the problem that ErbB2 activity can be increased even when ERBB2 is rarely amplified, enabling activity-based detection rather than copy-number-based inference.
Published Workflows
Objective: Identify mechanisms driving increased ErbB2 activity during androgen signaling inhibition and determine their role in progression to castration-resistant prostate cancer, while testing whether ErbB2 inhibition can suppress this adaptive state.
Why it works: The study combines protein-activity readouts, transcript measurements, and perturbation with an ErbB2 inhibitor across cell lines, xenografts, and clinical tumors to connect adaptive signaling changes with therapeutic vulnerability.
adaptive increase in ErbB2 signaling after androgen signaling inhibitionNRG1-mediated ErbB3/ErbB2 activationd16ERBB2 splice-variant contribution to ErbB2 activationimmunohistochemistryreverse-phase protein arrayRNA sequencingin vitro inhibitor sensitivity testingin vivo inhibitor sensitivity testing
Stages
- 1.Multimodal interrogation of ErbB2 signaling and candidate drivers(functional_characterization)
This stage establishes whether ErbB2 signaling is increased during ASI and CRPC and identifies candidate mechanisms that may drive that increase.
Selection: Measure ErbB2 activation and associated molecular features across cell lines, xenografts, and clinical tumors at various stages of castration resistance.
- 2.Therapeutic sensitivity testing of ErbB2 inhibition(confirmatory_validation)
This stage functionally validates whether the observed ErbB2 activation state is actionable with pharmacologic inhibition.
Selection: Test whether models with ErbB2 signaling remain sensitive to ErbB2 inhibitors in vitro and in vivo.
Taxonomy & Function
Primary hierarchy
Technique Branch
Method: A concrete measurement method used to characterize an engineered system.
Techniques
Functional AssayTarget processes
signalingImplementation Constraints
cofactor dependency: cofactor requirement unknownencoding mode: genetically encodedimplementation constraint: context specific validationoperating role: sensor
It requires tumor specimens and an antibody against phosphorylated ErbB2 for IHC analysis. The abstract does not provide the exact phospho-site or staining protocol.; requires an antibody against phosphorylated ErbB2; requires tumor tissue suitable for immunohistochemistry
The abstract does not show that this assay alone establishes mechanism or guarantees clinical response prediction. It also does not provide assay standardization details.; the abstract does not specify the phospho-epitope, scoring method, or predictive performance
Validation
Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication
Supporting Sources
Ranked Claims
ErbB2 phosphorylation may serve as a biomarker for tumors that will respond in CRPC.
ErbB2 phosphorylation may be a biomarker for tumors that will respond in CRPC.
Phospho-ErbB2-positive ErbB2 activation was present in approximately 26% of residual tumors after neoadjuvant androgen signaling inhibition and in advanced CRPC.
ErbB2 activation, identified by IHC with an antibody against phosphorylated ErbB2, was present in ∼26% of residual tumors in radical prostatectomies after neoadjuvant androgen signaling inhibition (ASI) and in advanced CRPC.
residual tumor prevalence with ErbB2 activation 26 %
Approval Evidence
1 source2 linked approval claimsfirst-pass slug phosphorylated-erbb2-immunohistochemistry
ErbB2 activation, identified by IHC with an antibody against phosphorylated ErbB2
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biomarker hypothesissupports
ErbB2 phosphorylation may serve as a biomarker for tumors that will respond in CRPC.
ErbB2 phosphorylation may be a biomarker for tumors that will respond in CRPC.
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prevalencesupports
Phospho-ErbB2-positive ErbB2 activation was present in approximately 26% of residual tumors after neoadjuvant androgen signaling inhibition and in advanced CRPC.
ErbB2 activation, identified by IHC with an antibody against phosphorylated ErbB2, was present in ∼26% of residual tumors in radical prostatectomies after neoadjuvant androgen signaling inhibition (ASI) and in advanced CRPC.
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Comparisons
Source-stated alternatives
The paper also interrogated ErbB2 signaling using reverse-phase protein array and RNA sequencing, which are alternative measurement approaches mentioned in the abstract.
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The paper also interrogated ErbB2 signaling using reverse-phase protein array and RNA sequencing, which are alternative measurement approaches mentioned in the abstract.
Source-backed strengths
used to identify activated ErbB2 in residual post-ASI tumors and advanced CRPC
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used to identify activated ErbB2 in residual post-ASI tumors and advanced CRPC
Compared with RNA sequencing
The paper also interrogated ErbB2 signaling using reverse-phase protein array and RNA sequencing, which are alternative measurement approaches mentioned in the abstract.
Shared frame: source-stated alternative in extracted literature
Strengths here: used to identify activated ErbB2 in residual post-ASI tumors and advanced CRPC.
Relative tradeoffs: the abstract does not specify the phospho-epitope, scoring method, or predictive performance.
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The paper also interrogated ErbB2 signaling using reverse-phase protein array and RNA sequencing, which are alternative measurement approaches mentioned in the abstract.
Ranked Citations
- 1.