FBXO7 EYA2 Inhibitors Block AXL Signaling
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Solution Overview
Problem
Current cancer treatments, such as immune checkpoint blockade therapy, often face resistance due to the modulation of immune checkpoint proteins like FBXO7 and EYA2, which allow cancer cells to evade the immune system, leading to treatment challenges.
Innovation Solution
Administering a therapeutically effective amount of a FBXO7 inhibitor, an EYA2 inhibitor, or a combination thereof, or a chemical entity that inhibits the interaction between FBXO7 and EYA2, to modulate their expression and activity in cancer cells, thereby enhancing the effectiveness of immune-based therapies.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If immune checkpoint blockade therapy is used to treat cancer, then cancer cells can be targeted by the immune system, but cancer cells develop resistance through modulation of immune checkpoint proteins (FBXO7 and EYA2) that allow them to evade the immune system
Solution Approach 1:
The patent introduces FBXO7 and EYA2 as intermediary proteins that mediate the immune evasion mechanism. By targeting these intermediary proteins with specific inhibitors, the cancer cells' ability to evade the immune system is disrupted, thereby restoring the effectiveness of immune checkpoint blockade therapy without directly targeting the immune checkpoint proteins themselves
Solution Approach 2:
The patent extracts and targets the specific proteins FBXO7 and EYA2 that are responsible for immune evasion. By removing or inhibiting these specific proteins from the cancer cell's evasion mechanism, the therapy can effectively overcome resistance while maintaining the original immune checkpoint blockade approach
2Adaptability or versatility
If FBXO7 and EYA2 are modulated in cancer cells, then immune checkpoint proteins are regulated to enable immune evasion, but this modulation leads to treatment resistance
Solution Approach 1:
Instead of directly targeting the immune checkpoint proteins that are typically inhibited in cancer cells, the patent inverts the approach by targeting the upstream regulators (FBXO7 and EYA2) that control the expression or activity of these checkpoint proteins. This inversion restores the immune system's ability to recognize and attack cancer cells by disrupting the regulatory mechanism rather than the effect itself
3Productivity
If FBXO7 inhibitor or EYA2 inhibitor is administered, then AXL signaling is reduced and tumor growth is attenuated, but the treatment mechanism becomes more complex
Solution Approach 1:
The patent segments the treatment mechanism into two distinct components: FBXO7 inhibition and EYA2 inhibition. These can be targeted separately or in combination, allowing for modular treatment strategies that can be adjusted based on the specific cancer type and patient response, thereby managing complexity through systematic breakdown of the therapeutic approach
Data Source
AI summary
Methods of treating cancer comprising targeting the FBXO7/EYA2-SCFFBXW7 axis, such as via EYA2 Tyr phosphatase inhibitors. As EYA2 acts downstream of SCFFBXW7, FBXO7/EYA2 inhibitors can be effective in blocking immune escape pathways and immunotherapy resistance in Fbxw7 mutant tumors. Furthermore, FBXO7/EYA2 inhibitors can be effective in mitigating AXL signaling and associated immune evasion, thus enhancing antitumor immune responses.