E-cadherin Biomarker for PTK2 Inhibitor Patient Stratification
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Solution Overview
Problem
Current PTK2 inhibitors lack predictive biomarkers for selecting cancer patients most likely to benefit from therapy, as their efficacy varies widely across different cancer models without clear genetic mutations or amplifications associated with sensitivity.
Innovation Solution
E-cadherin protein immunoreactivity score (IRS) is used to determine susceptibility to PTK2 inhibitors through immunohistochemistry, where scores of 0-2 indicate potential therapeutic benefit, allowing for the selection of cancer patients for treatment.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If PTK2 inhibitors are used to treat various cancer types, then cancer growth inhibition can be achieved in some models, but efficacy varies widely among different cancer models with no clear predictive biomarkers available
Solution Approach 1:
The patent changes the parameter used for patient selection from genetic mutations or amplifications (which showed no association with PTK2 inhibitor sensitivity) to protein expression levels. Specifically, it measures the expression level of E-cadherin protein in cancer tissue samples, where low expression levels predict sensitivity to PTK2 inhibitors. This parameter change provides a reliable, actionable biomarker for patient stratification.
2Loss of information
If genetic mutations or amplifications are analyzed to predict kinase inhibitor sensitivity (as done for EGFR, HER2, BRAF), then clear predictive biomarkers are available, but no such mutations or amplifications have been described for the PTK2 gene in human cancers
Solution Approach 1:
The patent substitutes the genetic analysis approach (looking for mutations or amplifications in the PTK2 gene) with a protein expression analysis approach. Instead of using DNA sequencing or gene copy number analysis, it employs immunohistochemistry to detect and quantify E-cadherin protein levels in cancer tissue. This substitution reveals that protein expression, rather than genetic alterations, is the relevant predictive factor for PTK2 inhibitor sensitivity.
3Productivity
If PTK2 inhibitors are administered without patient stratification, then all cancer patients receive potential treatment, but many patients will not benefit due to lack of predictive biomarkers
Solution Approach 1:
The patent performs preliminary assessment of E-cadherin protein expression levels in cancer tissue samples before initiating PTK2 inhibitor therapy. By measuring protein expression in advance (using immunohistochemistry on archival tissue samples or biopsy material), the method identifies patients likely to respond to treatment beforehand, allowing for optimized treatment selection without delaying therapy initiation.
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
The E-cadherin protein immunoreactivity score effectively predicts sensitivity to PTK2 inhibitors, enabling targeted treatment strategies and improving therapeutic outcomes for cancer patients by identifying those likely to benefit from PTK2 inhibitor therapy.
Implementation Method 1
a primary antibody which is specific for E-cadherin
Implementation Method 2
a secondary antibody which specifically reacts with the primary antibody
Data Source
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AI summary
The present invention relates to a method for determining whether a cancer patient is susceptible to treatment with a protein tyrosine kinase 2 (PTK2) inhibitor, comprising detecting the expression of the E-cadherin protein in a cancer sample of said cancer patient, wherein an E-cadherin protein immunoreactivity score (IRS) of 0-2 indicates that the cancer patient is susceptible to treatment with a PTK2 inhibitor. Said detection of the expression of the E-cadherin protein in a cancer sample of a cancer patient is preferably conducted by way of an immunohistochemistry (IHC) method. Said IHC method preferably employs a primary antibody which is specific for E-cadherin and a secondary antibody which specifically reacts with the primary antibody. The present invention also relates to a method of treating a cancer patient whose cancer is characterized by an E- cadherin protein immunoreactivity score (IRS) of 0-2, comprising administering to the patient a therapeutically effective amount of a PTK2 inhibitor. In a further aspect, the present invention relates to a PTK2 inhibitor for use in the treatment of a cancer patient whose cancer is characterized by an E-cadherin protein immunoreactivity score (IRS) of 0-2. The present invention also provides a method of screening for a therapeutically effective PTK2 inhibitor comprising the steps of (a) providing cancer cells or a cancer cell line which are characterized by an E-cadherin protein immunoreactivity score of 2, 1, or 0 (1 being preferred and 0 being even more preferred); (b) contacting the cancer cell or the cancer cell line of (a) with a PTK2 inhibitor; and (c) evaluating whether the PTK2 inhibitor negatively affects the cancer cell/cancer cell lines. In a further aspect, the present invention relates to a method for stratifying cancer patients that are susceptible to treatment with a PTK2 inhibitor, comprising determining the E-cadherin IRS score in a cancer sample of said patient, wherein an E-cadherin protein immunoreactivity score (IRS) of 0-2 (i.e. 2, 1, or 0) indicates that the cancer patient is susceptible to treatment with a PTK2 inhibitor. The present invention also relates to a pharmaceutical package comprising a PTK2 inhibitor, and (a) instructions and/or an imprint indicating that said PTK2 inhibitor is to be used for the treatment of patients which suffer from a cancer which is characterized by an E-cadherin protein immunoreactivity score of 2, 1, or 0 (1 being preferred and 0 being more preferred); and/or (b) instructions and/or an imprint indicating that said patient is to be stratified by a method of the present invention; and/or (c) means to carry out a method as defined herein.