SRM Mass Spectrometry for TYMP UCK2 Quantification in CRC
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Solution Overview
Problem
Current methods for determining protein presence in cancer patient tissue, especially FFPE tissue, are subjective and do not provide quantitative data predictive of sensitivity to therapeutic agents like 5-FU, leading to potential misclassification and suboptimal treatment decisions.
Innovation Solution
The use of SRM/MRM mass spectrometry to quantify specific peptide fragments of TYMP and UCK2 proteins in tumor cells, allowing for precise determination of protein levels and predicting patient response to chemotherapy regimens such as FOLFOX, enabling informed treatment decisions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If current methods for determining protein presence in cancer patient tissue are used, then the assessment can be performed, but the results are subjective and do not provide quantitative data predictive of sensitivity to therapeutic agents
Solution Approach 1:
The patent replaces subjective visual assessment methods with mass spectrometry technology to objectively quantify protein levels. The mass spectrometry system measures specific peptide fragments (TYMP and UCK2) to generate precise quantitative data, eliminating the subjectivity inherent in traditional protein presence determination methods and providing reliable predictive values for chemotherapy response.
2Measurement precision
If mass spectrometry is used to quantify protein levels, then accurate predictive data is obtained, but the device complexity and measurement difficulty increase
Solution Approach 1:
The patent employs targeted proteomics approaches where specific peptide fragments corresponding to TYMP and UCK2 proteins are pre-identified and selected for quantification. This preliminary selection of target peptides simplifies the complex mass spectrometry analysis by focusing measurement on specific biomarkers known to predict FOLFOX response, thereby reducing the overall measurement complexity while maintaining high precision.
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
Provides accurate and predictive quantitative data on TYMP and UCK2 protein levels, enabling clinicians to tailor chemotherapy regimens effectively, improving treatment outcomes and patient prognosis.
Implementation Method 1
determining whether or not the patient will clinically respond to treatment with the FOLFOX regimen by asaying tumor tissue surgically-removed from the patient and identifying those patients most likely to respond to treatment with the standard chemotherapy strategy
Data Source
AI summary
Methods are provided herein for identifying whether a cancer patient, for example a colorectal cancer patient, will be responsive to treatment with a therapeutic strategy comprising administration of the FOLFOX regimen (5-fluorouracil, leucovorin, and oxaliplatin). Specified TYMP and UCK2 fragment peptides are precisely detected and quantitated by SRM-mass spectrometry directly in tumor cells, for example colorectal cancer tumor cells, that are collected from tumor tissue obtained from a cancer patient and compared to reference levels in order to determine if the cancer patients will positively respond to treatment with the combination treatment of FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin).