TERT-Targeting Agents for Genotoxic Therapy Sensitization
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing cancer treatments face challenges with intrinsic resistance to genotoxic therapy and immune evasion, leading to therapy resistance and recurrence, due to the non-canonical roles of telomerase reverse transcriptase (TERT) in cancer cells, which are not adequately addressed by current inhibitors.
Innovation Solution
Targeting the biological activity of TERT with compounds that inhibit its non-canonical functions, sensitizing cancer cells to genotoxic therapy and enhancing immune responses, thereby overcoming resistance and promoting tumor elimination.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional telomerase inhibitors are used to block telomere elongation, then telomerase activity is inhibited, but cancer cells develop intrinsic resistance to genotoxic therapy and therapy resistance relapse
Solution Approach 1:
The invention segments the TERT protein into distinct functional domains (canonical telomere elongation function and non-canonical functions such as DNA repair, stress response, and immune evasion). By targeting specific non-canonical domains with selective inhibitors, the patent overcomes therapy resistance while maintaining efficacy against cancer cells that rely on these alternative TERT functions.
Solution Approach 2:
The patent changes the inhibition parameter from non-specific telomerase inhibition to specific inhibition of non-canonical TERT functions. By modifying the inhibition strategy to target specific functional domains rather than blocking all TERT activity, the invention achieves therapeutic efficacy while avoiding the development of therapy resistance that occurs with conventional inhibitors.
2Productivity
If TERT inhibitors are administered to treat cancer, then cancer cell proliferation is inhibited, but tumor cells evade immune surveillance and immune-mediated elimination
Solution Approach 1:
The invention extracts and specifically targets the non-canonical functions of TERT that are responsible for immune evasion (such as suppression of immune checkpoint expression and modulation of tumor microenvironment). By separating these harmful functions from the essential telomere maintenance function, the patent enables cancer cell growth control while removing the immune evasion capability.
Solution Approach 2:
The patent uses selective TERT inhibitors as intermediary agents that specifically block non-canonical TERT functions mediating immune evasion. These inhibitors act as mediators between the cancer cell and the immune system, preventing TERT from suppressing immune responses while allowing the immune system to effectively target and eliminate tumor cells.
3Object-affected harmful factors
If genotoxic therapy is used to treat cancer, then cancer cells are killed, but treatment resistance and recurrence occur due to non-canonical TERT functions
Solution Approach 1:
The invention applies preliminary action by administering TERT inhibitors that block non-canonical functions before or during genotoxic therapy. This preliminary inhibition of alternative survival pathways (DNA repair, stress response) enhances the effectiveness of genotoxic therapy and prevents the development of treatment resistance, leading to more durable responses and reduced recurrence.
Solution Approach 2:
The patent merges the inhibition of non-canonical TERT functions with genotoxic therapy in a combination treatment approach. By combining selective TERT inhibitors with chemotherapy or radiation, the invention creates a synergistic effect where the TERT inhibitor prevents resistance mechanisms while the genotoxic agent kills cancer cells, achieving both immediate tumor reduction and long-term treatment durability.
Data Source
AI summary
Disclosed herein are agents that target telomerase reverse transcriptase (TERT) for treating cancer and sensitizing cancer cells to genotoxic therapy. The methods include inhibiting induction of an immunosuppressive factor in a subject in need thereof, the method comprising administering an inhibitor of TERT to the subject.