SRM Mass Spectrometry for FR-α and GART Protein Quantitation
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Solution Overview
Problem
Current methods for determining therapeutic regimens for lung cancer patients are inadequate as they lack precision in predicting response to anti-cancer drugs like pemetrexed due to subjective and non-quantitative protein detection methods, leading to potential misclassification and inappropriate treatment.
Innovation Solution
A method using mass spectrometry-based Selected Reaction Monitoring (SRM/MRM) to quantify specific fragment peptides of Folate Receptor-alpha (FR-α) and Glycinamide Ribonucleotide Synthetase (GART) proteins in tumor tissue, allowing for precise determination of pemetrexed treatment regimens based on peptide levels, optionally including cisplatin.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If mass spectrometry-based SRM/MRM is used to quantify FR-α and GART proteins, then measurement precision is improved, but device complexity increases
Solution Approach 1:
The patent extracts and quantifies specific peptide fragments (SEQ ID NO: 1 from FR-α and SEQ ID NO: 2 from GART) from the complex protein mixture using mass spectrometry. By focusing on these specific peptide sequences rather than attempting to measure entire proteins, the method achieves high measurement precision while managing the complexity of the mass spectrometry system through targeted analysis.
2Reliability
If quantitative protein measurement methods are implemented, then treatment reliability is improved, but manufacturing precision requirements increase
Solution Approach 1:
The patent establishes a quantitative relationship between measured peptide levels and treatment response by comparing GART peptide levels to a reference level. This feedback mechanism allows clinicians to adjust treatment decisions based on precise measurements, improving treatment reliability while maintaining manageable precision requirements through established reference standards.
3Loss of information
If FR-α and GART protein levels are quantitated to determine treatment, then loss of information is reduced, but difficulty of detecting and measuring increases
Solution Approach 1:
The patent replaces traditional immunohistochemistry or Western blotting methods with mass spectrometry-based detection. This substitution provides more accurate and quantitative measurement of FR-α and GART protein levels, reducing information loss about biomarker status while managing detection difficulty through the use of specific peptide sequences and standardized protocols.
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 approach provides accurate and precise quantitation of FR-α and GART proteins, enabling tailored treatment strategies that enhance patient response to pemetrexed and reduce unnecessary toxicity, as evidenced by significant correlations with overall survival in lung cancer patients.
Implementation Method 1
The specified FR-α and GART peptides are detected using mass spectrometry-based Selected Reaction Monitoring (SRM), also referred to as Multiple Reaction Monitoring (MRM)
Data Source
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AI summary
Improved methods are provided for treating cancer patients, particularly patients suffering from lung cancer. Methods are provided for identifying whether a lung tumor will be responsive to treatment with a therapeutic regimen that includes pemetrexed and optionally includes cisplatin. A specific FR-α fragment peptide and a specific GART fragment peptide are precisely detected and quantitated by SRM-mass spectrometry directly in lung tumor cells collected from lung tumor tissue that was obtained from a cancer patient and compared to reference levels in order to determine if the lung cancer patient will positively respond to treatment with the c therapeutic regimen.