Melanoma Response Prediction Using Blood Phosphorylation Profiles
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Solution Overview
Problem
Current treatments for melanoma, particularly stage IV melanomas, are ineffective for many patients and associated with undesirable side effects, necessitating a need for biomarkers to predict individual patient responses to targeted pharmacotherapy.
Innovation Solution
Measuring kinase and/or phosphatase activity in a patient's blood sample, specifically through phosphorylation profiles of peptide markers, to predict the response to medications like Ipilimumab, Nivolumab, and Pembrolizumab, using phosphorylation profiles and classifier parameters.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current treatments (dacarbazine, interferon-alpha, interleukin-2) are used for metastatic melanoma, then treatment can be administered, but the 5-year survival rate remains poor at 16% or less
Solution Approach 1:
The patent applies preliminary action by measuring kinase and phosphatase activity in blood samples before treatment to predict patient response. This pre-treatment assessment allows clinicians to identify good responders versus poor responders in advance, preventing ineffective treatment administration and enabling selection of appropriate therapies before committing patients to treatments with poor survival outcomes
Solution Approach 2:
The patent introduces phosphorylation profiles as an intermediary biomarker system that mediates between the treatment and the patient outcome. By measuring phosphorylation levels of specific peptide markers in blood samples, the system provides an indirect but accurate prediction of treatment response, serving as a bridge between treatment administration and survival outcome
2Reliability
If new treatments (kinase inhibitors, immunotherapy) are developed, then survival improvement may be achieved, but it is unclear which patients will respond without biomarker prediction
Solution Approach 1:
The patent replaces the mechanical/systematic approach of trial-and-error treatment selection with a biochemical measurement system. Instead of administering treatments and observing outcomes (mechanical observation), the system uses in vitro phosphorylation assays to directly measure and predict treatment response through biochemical interactions between kinases/phosphatases and substrate peptides
Solution Approach 2:
The patent introduces phosphorylation profiles as an intermediary biomarker system that mediates between the treatment and the patient outcome. By measuring phosphorylation levels of specific peptide markers in blood samples, the system provides an indirect but accurate prediction of treatment response, serving as a bridge between treatment administration and survival outcome
3Productivity
If treatments are administered without response prediction, then all patients receive treatment, but resources are wasted on poor responders and adverse effects occur
Solution Approach 1:
The patent applies preliminary anti-action by identifying poor responders through phosphorylation profiling before treatment administration. This allows clinicians to prevent or avoid administering treatments that would be ineffective or cause adverse effects in these patients, thereby preemptively counteracting the harmful effects before they occur
Solution Approach 2:
The patent extracts the predictive information about treatment response from complex patient biology by measuring specific kinase and phosphatase activities in blood samples. This extraction of relevant biomarker information from the complex biological system enables selective treatment assignment, separating good responders from poor responders to optimize resource allocation and minimize harm
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 prediction of treatment outcomes with high correlation, allowing for personalized treatment strategies and reducing adverse effects by identifying good and poor responders.
Implementation Method 1
measuring the kinase and/or phosphatase activity by contacting the sample with at least one substrate for a protein kinase and/or at least one substrate for a protein phosphatase, thereby providing a phosphorylation profile of the sample
Implementation Method 2
measuring the kinase and/or phosphatase activity of a sample, obtained from said patient diagnosed with melanoma, by contacting said sample with at least one protein kinase substrate and/or at least one protein phosphatase substrate
Data Source
AI summary
The present invention relates to a method for determining or predicting the response of a patient diagnosed with melanoma to targeted pharmacotherapy. The present invention also aims to provide methods and devices for predicting the response of patients diagnosed with melanoma to specific medicaments. More specifically, the present invention provides methods which measure kinase and/or phosphatase activity by studying phosphorylation levels and profiles and inhibitions thereof by drugs in samples, preferably blood samples, of said patients.


