K-ras Mutation Detection for Anti-EGFR Therapy Selection
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Solution Overview
Problem
Current treatments with panitumumab, an anti-EGFr antibody, are ineffective for patients with colorectal adenocarcinoma harboring specific K-ras mutations such as G12S, G12V, G12D, G12A, G12C, and G13D, as these mutations confer nonresponsiveness to the therapy.
Innovation Solution
An in vitro method to predict nonresponsiveness to panitumumab treatment by determining the presence of these specific K-ras mutations in tumor samples, allowing for personalized treatment approaches.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If panitumumab therapy is administered to all colorectal adenocarcinoma patients, then treatment coverage is maximized, but treatment effectiveness is reduced due to nonresponsiveness in patients with specific K-ras mutations
Solution Approach 1:
The patent applies preliminary action by performing K-ras mutation testing on tumor samples before initiating panitumumab therapy. This predictive testing identifies patients with nonresponsiveness mutations (G12S, G12V, G12D, G12A, G12C, G13D) in advance, allowing clinicians to avoid ineffective treatment and select alternative therapies, thereby improving overall treatment effectiveness while maintaining appropriate coverage for responsive patients
2Reliability
If K-ras mutation testing is performed on all patients, then treatment effectiveness is improved by avoiding nonresponsive cases, but diagnostic complexity and cost increase
Solution Approach 1:
The patent applies local quality by focusing the diagnostic approach on specific, high-impact K-ras mutations (G12S, G12V, G12D, G12A, G12C, G13D) rather than进行全面 genomic sequencing. This targeted testing of particular mutation sites provides sufficient predictive value for panitumumab responsiveness while minimizing diagnostic complexity and cost, making the testing feasible for routine clinical use
Data Source
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AI summary
The present application relates to K-ras mutations, to polynucleotides encoding mutant K-ras polypeptides, and to methods of identifying K-ras mutations. The present application also relates to methods of diagnosing cancer; and methods and kits for predicting the usefulness of anti-EGFr specific binding agents in the treatment of tumors.