Cyclin E1 Stratification for Azenosertib WEE1 Inhibitor Therapy
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Solution Overview
Problem
Current cancer treatments are ineffective for subjects with DNA damage repair defects due to improper DNA repair leading to cell death and tumor progression, as they do not account for individual variations in Cyclin E1 expression levels.
Innovation Solution
Selecting subjects based on a predetermined Cyclin E1 biomarker threshold, such as increased Cyclin E1 protein expression, to administer WEE1 inhibitor Azenosertib, either alone or in combination with a second chemotherapeutic agent, to enhance treatment efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If cancer treatment is administered without considering Cyclin E1 expression levels, then treatment coverage is broad, but treatment efficacy is reduced due to individual variations in DNA repair capacity
Solution Approach 1:
The patent applies preliminary action by measuring Cyclin E1 expression levels before administering WEE1 inhibitor treatment. This pre-treatment biomarker assessment identifies patients with high Cyclin E1 expression who are most likely to respond to WEE1 inhibition, allowing clinicians to select the most appropriate treatment strategy in advance and avoid ineffective therapies for patients with low Cyclin E1 expression
Solution Approach 2:
The patent applies local quality by tailoring treatment to specific patient subgroups based on their Cyclin E1 expression status. Instead of uniform treatment, patients are stratified into high Cyclin E1 expressors who benefit from WEE1 inhibition and other groups who may require alternative approaches, optimizing treatment efficacy for each specific patient population
2Reliability
If WEE1 inhibitor is used as monotherapy, then treatment simplicity is maintained, but treatment efficacy is limited compared to combination therapy
Solution Approach 1:
The patent applies merging by combining WEE1 inhibitor treatment with other chemotherapeutic agents for patients with high Cyclin E1 expression. This combination approach leverages the synergistic effect where WEE1 inhibition enhances the cytotoxicity of DNA-damaging chemotherapy agents, improving overall treatment efficacy while the Cyclin E1 biomarker guides which patients should receive this more complex combination regimen
Data Source
AI summary
The present disclosure provides, among other things, methods for treating cancer comprising administering an effective dose of Azenosertib to subjects selected to have a Cyclin E1 status above a predetermined threshold.