SRM/MRM Mass Spectrometry Assay for FGFR2 Protein Quantification
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Solution Overview
Problem
Current cancer treatments, including traditional chemotherapeutic agents and targeted therapies, often harm normal cells along with cancer cells, and there is a need for more precise methods to determine the effectiveness of FGFR2-targeted therapeutic agents, which are only beneficial for patients with high FGFR2 protein expression in their cancer cells.
Innovation Solution
A quantitative proteomics-based assay using mass spectrometry, specifically a Selected Reaction Monitoring (SRM)/Multiple Reaction Monitoring (MRM) assay, to measure FGFR2 protein levels in formalin-fixed cancer patient tissues, enabling accurate determination of FGFR2 protein activation and guiding personalized treatment decisions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional chemotherapeutic agents are used to treat cancer, then cancer cells are killed, but normal cells are also harmed
Solution Approach 1:
The patent applies local quality by developing targeted therapies that specifically attack FGFR2 protein only in cancer cells where it is overexpressed, rather than using non-specific chemotherapeutics that harm all rapidly dividing cells. The therapy is localized to affect only the specific protein target in the specific cell type.
Solution Approach 2:
The patent uses FGFR2 protein expression level as an intermediary marker to identify and select patients who will benefit from targeted therapy. By measuring FGFR2 levels in tumor tissue, the system determines which patients are candidates for FGFR2-targeted agents, thereby avoiding treatment of patients whose cancer cells do not express the target protein.
2Adaptability or versatility
If FGFR2-targeted therapeutic agents are used, then cancer cells with high FGFR2 expression are treated specifically, but treatment effectiveness varies by patient
Solution Approach 1:
The patent implements feedback by measuring FGFR2 protein levels in patient tumor tissue before treatment and using this information to determine whether the patient is a candidate for FGFR2-targeted therapy. This pre-treatment assessment feedback loop ensures that therapy is only administered to patients whose cancer cells express sufficient levels of the target protein, thereby improving treatment effectiveness consistency.
3Measurement precision
If mass spectrometry-based SRM/MRM assay is used to measure FGFR2 protein levels, then quantitative measurement precision is improved, but assay complexity increases
Solution Approach 1:
The patent extracts and identifies specific peptide sequences from the FGFR2 protein that serve as reliable surrogates for measuring overall protein levels. By focusing on specific peptide fragments that can be reliably detected and quantified by mass spectrometry, the system simplifies the measurement process while maintaining precision.
Solution Approach 2:
The patent uses peptide sequences as copies or surrogates of the full FGFR2 protein. Instead of directly measuring the complex protein, the system measures specific peptide fragments that contain characteristic sequences, thereby simplifying the analytical process while maintaining quantitative accuracy.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
This method provides precise quantitative measurements of FGFR2 protein levels, aiding in cancer diagnosis, prognosis, and selecting appropriate therapeutic agents, thereby improving treatment outcomes by targeting cancer cells specifically.
Implementation Method 1
The methods described below provide a quantitative proteomics-based assay that delivers a relevant measure of activation of the FGFR2 signal pathway... In particular, the methods provide a mass spectrometry assay that quantifies FGFR2 in formalin fixed tissues from cancer patients
Data Source
AI summary
Methods are provided for quantifying the fibroblast growth factor receptor 2 protein (FGFR2) directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring (SRM)/Multiple Reaction Monitoring (MRM) mass spectrometry. The biological sample may be selected from tissues and cells treated with formaldehyde containing agents/fixatives including formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells. A protein sample is prepared from the biological sample and the FGFR2 protein is quantitated in the sample using the method of SRM/MRM mass spectrometry by quantitating in the protein sample at least one fragment peptide derived from FGFR2.