CDK4/6 Inhibitor Response Prediction via Biomarker Panel Analysis
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Solution Overview
Problem
Current CDK4/6 inhibitor therapies for neoplastic diseases, such as breast cancer, face challenges in identifying patients who would benefit from treatment due to severe side effects and variable response rates, necessitating a method to predict response or resistance based on specific biomarker expressions.
Innovation Solution
Determining the expression levels of markers like PD-L1, PIAS2, MAP2K6, DSG3, ABCC12, and IFT52 in patient samples to predict the response or resistance to CDK4/6 inhibitor therapy, allowing for personalized treatment decisions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If CDK4/6 inhibitor therapy is administered to patients with hormone-receptor positive, HER2-negative breast cancer, then the treatment may achieve anti-cancer effects by preventing overproliferation of cancer cells, but severe side effects occur including nausea, diarrhea, fatigue, neutropenia, leukopenia, anemia, and thrombocytopenia
Solution Approach 1:
The patent applies preliminary action by determining marker expression levels (such as PD-L1, PIAS2, MAP2K6, DSG3, ABCC12, and IFT52) before administering CDK4/6 inhibitor therapy. This pre-treatment assessment identifies patients likely to respond benefitously, allowing clinicians to predict treatment outcome in advance and avoid subjecting non-responders to severe side effects. The marker analysis is performed on patient samples prior to treatment initiation, enabling proactive treatment selection.
2Productivity
If CDK4/6 inhibitor therapy is administered to all patients with hormone-receptor positive, HER2-negative breast cancer, then more patients may potentially benefit from treatment, but unnecessary treatment is administered to non-responders exposing them to severe side effects
Solution Approach 1:
The patent applies local quality by differentiating patient subgroups based on their specific marker expression profiles. Instead of uniform treatment for all hormone-receptor positive, HER2-negative breast cancer patients, the invention identifies distinct subsets of patients with specific marker patterns (combinations of PD-L1, PIAS2, MAP2K6, DSG3, ABCC12, and IFT52 expression levels) who are more likely to respond. This allows tailored treatment assignment where only patients with favorable marker profiles receive CDK4/6 inhibitors, while others receive alternative therapies, thereby eliminating unnecessary treatment exposure.
3Adaptability or versatility
If marker expression analysis is performed to predict treatment response, then personalized treatment decisions can be made to avoid unnecessary treatment, but the complexity of determining multiple marker expression levels increases
Solution Approach 1:
The patent applies segmentation by dividing the complex marker analysis into discrete, independently determinable components. The invention specifies a defined panel of markers (PD-L1, PIAS2, MAP2K6, DSG3, ABCC12, and IFT52) that can be assessed separately through standard laboratory techniques. Each marker's expression level is determined independently, and the results are integrated to generate an overall response prediction. This segmented approach makes the complex analysis manageable and implementable in clinical settings using routine diagnostic procedures.
Data Source
AI summary
The present invention relates to a method for predicting a response or resistance to and/or a benefit from treatment with an inhibitor of cyclin-dependent kinases 4 (CDK4/6 inhibitor) in a subject suffering from a neoplastic disease, particularly breast cancer, comprising the step of: determining in a sample obtained from said subject the expression level of at least one marker selected from the group consisting of PD-L1, PIAS2, MAP2K6, DSG3, ABCC12, IFT52, ABCB6, ABCC1, ABCA5, ABCC6, ABCC11, CHUK, SUMO1, TDG, AURKA, SMC3, IKBKG and XPC, wherein the expression level of the at least one marker is indicative for predicting the response or resistance to and/or the benefit from the treatment with the CDK4/6 inhibitor in said subject. The invention further pertains to a CDK4/6 inhibitor for use in the treatment of neoplastic disease, particularly breast cancer, in a subject, wherein the subject has been determined to have a benefit from treatment with a CDK4/6 inhibitor in a method of the invention.