FGFR2-VCL Fusion Detection and Targeted Kinase Inhibition
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Solution Overview
Problem
Current cancer therapies lack specificity in targeting cancer-promoting fusion genes, leading to inadequate treatment outcomes for patients, as not all relevant fusion genes are discovered, and existing diagnostic methods are insufficient for identifying specific subpopulations that benefit from kinase inhibitors.
Innovation Solution
Development of cDNA encoding a fusion polypeptide comprising an FGFR2 and VCL polypeptide, which includes specific amino acid substitutions, deletions, or insertions, along with corresponding polynucleotide sequences, vectors for expression, and kits for detecting these fusion polypeptides, enabling targeted therapeutic approaches and diagnostic methods.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current cancer therapies are used to target fusion genes, then treatment coverage is provided, but specificity is insufficient leading to inadequate treatment outcomes
Solution Approach 1:
The patent segments the diagnostic and therapeutic approach by identifying specific fusion gene types (FGFR3-TACC3, FGFR2-VCL, etc.) and matching them with targeted kinase inhibitors. This segmentation allows for precise diagnostic identification of fusion subtypes and corresponding tailored therapeutic interventions, resolving the contradiction between broad treatment coverage and diagnostic specificity.
Solution Approach 2:
The patent changes the diagnostic parameter from general cancer detection to specific fusion gene identification through molecular testing. By implementing specific molecular diagnostics that detect fusion transcripts and proteins, the system achieves higher measurement precision in identifying targetable fusion subtypes, which directly improves treatment effectiveness through matched therapy.
2Adaptability or versatility
If comprehensive fusion gene detection is implemented, then more cancer subtypes are identified, but diagnostic method complexity increases
Solution Approach 1:
The patent employs universal diagnostic approaches that can detect multiple fusion gene types using common molecular biology techniques (RT-PCR, FISH, NGS). These multi-functional diagnostic tools can identify various fusion partners (TACC3, VCL, CCDC147, etc.) through standardized protocols, achieving comprehensive detection coverage without proportionally increasing system complexity.
3Measurement precision
If specific kinase inhibitors are used for fusion genes, then treatment precision is improved, but not all fusion genes are discovered leading to limited applicability
Solution Approach 1:
The patent performs preliminary comprehensive molecular characterization to identify the specific fusion gene type before selecting the appropriate kinase inhibitor. By conducting upfront fusion detection through multiple methodologies (transcript analysis, protein detection), the system ensures that the most suitable targeted therapy is selected for each patient's specific fusion subtype, maximizing both precision and applicability.
Data Source
Figure 1A~1B
Figure 2
Figure 3(A)~3(C)
AI summary
The present invention relates to fusion polypeptides comprising an FGFR2 polypeptide and to cDNAs encoding such fusion polypeptides. The invention also encompasses methods of diagnosing the presence of the fusion polypeptides or of a gene or RNA sequence coding therefore in a sample from a subject as well as methods of treatment of a tumor instructed by the latter diagnosis.