SHP-2 Gene Mutations in c-KIT Dependent Melanoma Detection
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Solution Overview
Problem
Current methods fail to effectively detect and treat c-KIT-dependent melanomas, particularly those occurring on acral, mucosal, and chronically sun-exposed skin, as they often lack mutations in BRAF and NRAS, and previous investigations have underestimated the role of c-KIT in melanoma progression.
Innovation Solution
The development of methods to detect c-KIT-dependent melanomas through sequence mutations and amplifications in the c-KIT gene, including SHP2 mutations, and the use of c-Kit inhibitors such as imatinib mesylate, dasatinib, or sunitinib to inhibit melanoma cell proliferation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If current detection methods are used for melanoma, then detection is possible, but detection accuracy is insufficient for c-KIT-dependent melanomas lacking BRAF and NRAS mutations
Solution Approach 1:
The patent changes the detection parameter from BRAF/NRAS mutation status to c-KIT mutation status and SHP2 expression levels. This parameter change enables accurate detection of c-KIT-dependent melanomas that were previously undetectable by standard BRAF/NRAS testing methods
Solution Approach 2:
The patent introduces SHP2 as an intermediary marker to detect c-KIT-dependent melanomas. Since SHP2 is downstream of c-KIT in the signaling pathway and shows altered expression in response to c-KIT activation, it serves as a reliable intermediary indicator for tumors that lack direct BRAF/NRAS mutations
2Reliability
If c-KIT role in melanoma is underestimated, then treatment options are limited, but accurate detection and treatment of c-KIT-dependent melanomas improves outcomes
Solution Approach 1:
The patent performs preliminary detection of c-KIT mutations and SHP2 expression levels before initiating treatment. This preliminary action identifies patients who will respond to c-Kit inhibitors, preventing loss of treatment opportunity and enabling targeted therapy selection before standard treatment fails
Solution Approach 2:
The patent establishes a feedback mechanism where SHP2 expression levels and c-KIT mutation status are used to predict treatment response to c-Kit inhibitors. This feedback loop allows clinicians to select appropriate targeted therapies based on molecular profiling, improving treatment effectiveness while avoiding ineffective standard therapies
Data Source
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AI summary
The present invention provides methods of detecting c-KIT-dependent- melanoma for diagnostic and prognostic purposes. The invention further provides methods of treating such melanoma by inhibiting c-KIT.