SERCA2 Inhibitor and STING Activator Combination for Cancer Treatment
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current STING modulators for treating inflammation-related pathologies, such as cancer and viral infections, face challenges with side effects and therapeutic resistance, and existing treatments for autoimmune diseases with chronic STING activation are inadequate, necessitating alternative strategies to improve efficacy and reduce inflammation.
Innovation Solution
The use of SERCA2 modulators, specifically inhibitors and activators, to regulate the STING pathway by binding to SERCA2, either inhibiting or activating its activity to enhance interferon responses and modulate inflammation, thereby potentiating the effects of STING agonists or reducing chronic inflammation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If direct STING activation is used to treat cancer, then anti-tumor immune response is enhanced, but side effects such as metabolic modulation and T lymphocyte apoptosis occur
Solution Approach 1:
The patent introduces SERCA2 as an intermediary component in the STING activation pathway. Instead of directly activating STING, the invention uses SERCA2 inhibitors to indirectly modulate STING activity through calcium signaling. This intermediary mechanism achieves anti-tumor efficacy while potentially reducing direct activation side effects by utilizing the endogenous SERCA2-STING interaction pathway
Solution Approach 2:
The invention changes the activation parameter from direct STING activation to indirect activation via SERCA2 modulation. By targeting SERCA2 activity (a different parameter in the signaling pathway), the patent achieves STING pathway activation with altered kinetics and potentially reduced toxic effects, as demonstrated by the use of SERCA2 inhibitors to potentiate STING agonist effects at lower doses
2Reliability
If high doses of STING agonists are administered to overcome therapeutic resistance, then anti-tumor efficacy is improved, but side effects are intensified
Solution Approach 1:
The patent introduces dynamic modulation of the STING pathway through combination therapy. SERCA2 inhibitors dynamically enhance the sensitivity of the STING pathway to agonists, allowing for dose reduction. This dynamic interaction creates a synergistic effect where the combination achieves superior efficacy at lower overall doses compared to monotherapy, thereby reducing side effect intensity
Solution Approach 2:
The invention employs preliminary action by pre-conditioning the immune system with SERCA2 inhibition before or concurrent with STING agonist administration. This preliminary modulation of calcium signaling pathways primers the system to respond more effectively to subsequent STING activation, enabling therapeutic efficacy at reduced doses and minimizing side effects
3Object-affected harmful factors
If JAK inhibitors are used to treat autoimmune diseases with chronic STING activation, then interferon signaling is blocked, but susceptibility to pathogen infection increases
Solution Approach 1:
The patent extracts the problematic chronic STING activation state by targeting upstream calcium signaling through SERCA2 modulation. By removing the excessive calcium flux that drives pathological STING activation, the invention reduces inflammation in autoimmune diseases without completely blocking interferon signaling, thereby maintaining some protective immunity against pathogens
Solution Approach 2:
The invention applies partial action by selectively modulating SERCA2 activity to reduce chronic STING activation without completely abolishing interferon responses. The controlled inhibition of SERCA2 achieves sufficient reduction of pathogenic inflammation while preserving baseline immune function, avoiding the excessive suppression seen with JAK inhibitors
Data Source
AI summary
The invention relates to products comprising at least one inhibitor of SERCA2 (Sarco/Endoplasmic Reticulum Ca2+−AT-Pase 2) according to the invention, and at least one activator of STING, as combination products for a simultaneous, separate or sequential use in the treatment and/or prevention of a cancer.