SLC7A11-Targeted Redox Modulation for Selective Cancer Cell Elimination
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Solution Overview
Problem
Current therapeutic strategies for managing cellular and systemic redox dysregulations, particularly in cancer and infectious diseases, lack effective small molecules that can selectively act as antioxidants or pro-oxidants to target specific cell populations, such as cancer cells, due to the complexity of redox balance and oxidative stress mechanisms.
Innovation Solution
A pharmaceutical composition comprising cytotoxic agents and cytotoxicity enhancing agents, including compounds that target the SLC7A11 gene and its encoded cystine/glutamate transporter protein, which increase the expression and activity of these proteins, thereby enhancing the cytotoxicity of selenium-containing compounds like sodium selenite and selenocystine, leading to synergistic cytotoxic effects in cancer cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If pro-oxidant agents are used to eliminate cancer cells, then cytotoxicity against cancer cells is improved, but toxicity to normal cells increases
Solution Approach 1:
The patent applies local quality by creating a differential effect where the same pharmaceutical composition exhibits pro-oxidant cytotoxicity specifically in cancer cells while maintaining safety in normal cells. This is achieved through the selective activation of the composition's components within the cancer cell environment, particularly through the modulation of SLC7A11 expression and the unique redox state of cancer cells, thereby localizing the harmful oxidative effect only where needed.
Solution Approach 2:
The patent utilizes parameter changes by exploiting differences in redox parameters between cancer and normal cells. The pharmaceutical composition modifies the redox state parameter selectively in cancer cells through the action of selenium compounds and cystine/glutamate transporter modulation, triggering apoptosis in cancer cells while normal cells with different redox parameters remain unaffected.
2Object-affected harmful factors
If antioxidant capacity is increased to mitigate oxidative stress, then protection against oxidative damage is improved, but ability to eliminate cancer cells deteriorates
Solution Approach 1:
The patent applies inversion by reversing the conventional approach: instead of using antioxidants to protect cells, it uses pro-oxidant agents to eliminate cancer cells. The pharmaceutical composition inverts the protective antioxidant strategy into a therapeutic pro-oxidant strategy that selectively kills cancer cells while the body's endogenous antioxidant systems protect normal cells.
Solution Approach 2:
The patent converts the harmful oxidative stress that normally damages cells into a beneficial therapeutic mechanism. By administering selenium-containing compounds that generate controlled oxidative stress, the composition transforms the harmful effect of reactive oxygen species into a beneficial cancer-killing mechanism, while the body's antioxidant defenses convert this oxidative stress into selective cytotoxicity against cancer cells.
3Reliability
If SLC7A11 expression is increased to enhance cytotoxicity, then synergistic cytotoxic effect is improved, but cellular redox balance deteriorates
Solution Approach 1:
The patent applies preliminary action by first modulating SLC7A11 expression and cellular redox state before administering the full therapeutic effect of the selenium compounds. The composition prepares the cancer cell environment by altering transporter expression and redox parameters in advance, making the cells more susceptible to the subsequent cytotoxic action of the selenium-containing agents.
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 composition significantly increases the cytotoxicity of selenium compounds against cancer cells, inducing redox stress and apoptosis, while maintaining minimal toxicity to normal cells, thus providing a therapeutic approach for treating various cancers and potentially infectious diseases.
Implementation Method 1
the one or more cytotoxicity enhancing agent(s) is a cystine/glutamate transporter protein (also known as xCT) encoded by human SLC7A11 gene
Implementation Method 2
inducing redox stress and apoptosis
Implementation Method 3
inducing redox stress and apoptosis
Data Source
AI summary
Disclosed herein are compositions and methods for increasing the expression of human SLC7A11. The compositions include a combination of compounds that exhibit anti-proliferative activity against cancer cells. The compositions and methods can be used to treat a subject with cancer. Disclosed are also compositions and methods of treating a coronavirus infection, Zika virus, influenza virus infection, human immunodeficiency virus (HIV), or Rhinovirus.