Integrin β4 Phosphorylation Predicts Src Kinase Inhibitor Response
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Solution Overview
Problem
Current methods lack reliable means to predict the responsiveness of tumor cells or individuals to inhibitors of the Src family kinases, such as dasatinib, bosutinib, and saracatinib, which are used in cancer treatment, leading to suboptimal treatment outcomes.
Innovation Solution
Evaluating the phosphorylation status of integrin β4, specifically at sites S1518, S1457, and T1455, to determine the responsiveness of tumor cells or individuals to these inhibitors, as an increase in phosphorylation at these sites indicates sensitivity to the treatment.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If targeted drugs like dasatinib, bosutinib, or saracatinib are used to treat cancer, then the treatment is more precise and less toxic compared to traditional chemotherapy, but the proportion of patients that benefit from these drugs is smaller
Solution Approach 1:
The patent applies preliminary action by evaluating the phosphorylation status of integrin β4 before initiating treatment with Src family kinase inhibitors. This pre-treatment assessment predicts which patients will respond to the therapy, allowing clinicians to select the most appropriate treatment approach in advance, thereby improving treatment predictability while maintaining the low toxicity benefits of targeted therapy.
2Ease of operation
If predictive tests based on a single marker linked to the drug target are used, then the test is simple and widely applicable, but the prediction accuracy of treatment response is insufficient
Solution Approach 1:
The patent applies parameter changes by shifting from evaluating the expression level of integrin β4 to evaluating its phosphorylation status at specific sites (S1518, S1457, T1455). This change in the measured parameter provides more accurate prediction of treatment response to Src family kinase inhibitors, as phosphorylation status directly reflects pathway activation and drug sensitivity, thereby improving measurement precision while maintaining operational simplicity through established phosphorylation detection methods.
Data Source
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AI summary
The present invention relates to a method for predicting the responsiveness of a mammalian tumor cell or cancer cell to an inhibitor of a kinase of the Src family, such as dasatinib, bosutinib. saracitinib or ponatinib. The present invention also provides for a method for predicting the responsiveness of an individual to an inhibitor of a kinase of the Src family, whereby the individual is suspected to suffer from cancer. These methods involve the evaluation of the status of integrin ß4, wherein said status is indicative for the responsiveness to the inhibitor. Furthermore, a kit useful for carrying out the methods described herein as well as an oligo- or polynucleotide and/or antibodies capable of detecting the expression level of integrin ß4 for predicting the responsiveness to the inhibitor are provided.