rhTRAIL Sensitivity Prediction via Death Receptor Expression
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current cancer therapies for metastatic malignant melanoma are inefficient, have temporary anti-tumor effects, and are associated with significant side effects, leading to low survival rates and a lack of standard therapeutic regimens.
Innovation Solution
The use of recombinant human Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (rhTRAIL) combined with the polyphenol quercetin to sensitize cancer cells to apoptosis, increasing the membrane expression of death receptors DR4 and DR5 and reducing anti-apoptotic proteins like FLIP, thereby overcoming resistance to rhTRAIL treatment.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current cancer therapies (chemotherapy, radiation therapy, targeted therapy and immunotherapy) are used to treat metastatic malignant melanoma, then anti-tumor effects are achieved, but the treatment is characterized by slow efficacy, temporary anti-tumor properties due to acquired resistance, and high degree of negative side effects
Solution Approach 1:
The patent changes the therapeutic parameter from conventional chemotherapy/radiation to rhTRAIL-based apoptosis induction. This parameter change enables selective targeting of cancer cells through death receptor-mediated apoptosis pathways, achieving effective anti-tumor activity while sparing normal cells from toxic effects, thus resolving the contradiction between efficacy and side effects
Solution Approach 2:
The patent introduces rhTRAIL as an intermediary substance that mediates selective apoptosis in cancer cells. rhTRAIL binds to death receptors (DR4, DR5) on cancer cell surfaces, triggering apoptosis specifically in malignant cells while leaving normal cells unaffected, thereby achieving effective tumor control with minimal side effects
2Reliability
If current cancer therapies are used to treat metastatic malignant melanoma, then some anti-tumor effects are achieved, but the treatment duration is limited due to acquired resistance
Solution Approach 1:
The patent performs preliminary assessment of death receptor expression levels (DR4, DR5) on tumor cells before initiating rhTRAIL therapy. This preliminary action identifies patients whose tumors are likely to respond to rhTRAIL treatment, enabling selection of appropriate candidates and predicting treatment durability before therapy begins
Solution Approach 2:
The patent employs feedback mechanisms by measuring death receptor expression levels and using this information to guide treatment decisions. The assessment of DR membrane expression provides feedback on likely treatment response, allowing for personalized therapy selection and potentially extending treatment duration by identifying patients who will maintain response over time
3Reliability
If death receptor membrane expression is assessed to determine rhTRAIL sensitivity, then treatment suitability can be identified, but additional testing time and complexity are required
Solution Approach 1:
The patent applies partial action by assessing only the specific death receptor expression levels (DR4, DR5) that are most predictive of rhTRAIL sensitivity, rather than performing comprehensive molecular profiling. This focused approach provides sufficient predictive information while minimizing testing time and complexity
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The combination of rhTRAIL and quercetin effectively induces apoptosis in previously resistant malignant melanoma cells, enhancing treatment efficacy while minimizing side effects by selectively targeting cancer cells.
Implementation Method 1
recombinant human Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (rhTRAIL) holds great promise as a cancer therapy due to its selectivity for cancer cells
Implementation Method 2
selective pro-apoptotic activity towards cancer cells and not non-transformed cells
Implementation Method 3
an increase of the proteasome-mediated degradation of the anti-apoptotic protein FLIP
Implementation Method 4
Quercetins action is manifested by the upregulation of rhTRAIL-binding receptors DR4 and DR5 on the surface of cancer cells
Implementation Method 5
Treatment with quercetin can modulate cellular components responsible for rhTRAIL-resistance
Data Source
AI summary
Disclosed are methods and compositions for identifying and treating certain conditions and diseases. In certain instances, the general inventive concepts provide methods for determining rhTRAIL sensitivity of a sample and/or methods and compositions for inducing apoptosis to treat conditions and diseases with rhTRAIL.