Dithio Compounds Sensitize Cancer Cells to Chemotherapy
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Solution Overview
Problem
Current cancer treatments fail to effectively increase patient survival time in cancers with overexpressed thioredoxin or glutaredoxin, as these proteins confer resistance to chemotherapy and radiation, leading to reduced therapeutic efficacy.
Innovation Solution
Administration of oxidative metabolism-affecting compounds, such as the disodium salt of 2,2′-dithio-bis-ethane sulfonate (Tavocept™), which modulate thioredoxin and glutaredoxin pathways, reducing their levels and activity to enhance chemotherapy sensitivity and efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If chemotherapy is administered to cancer patients with overexpressed thioredoxin or glutaredoxin, then the cancer cells exhibit resistance to the treatment, but patient survival time remains short
Solution Approach 1:
The patent applies preliminary action by administering dithio-containing compounds (such as mesna or N-acetylcysteine) before chemotherapy treatment to deplete intracellular glutathione levels in cancer cells. This pre-treatment creates a vulnerable state in the cancer cells, eliminating their resistance mechanism before the chemotherapeutic agent is introduced, thereby enhancing the subsequent chemotherapy efficacy and extending patient survival time
2Object-affected harmful factors
If thioredoxin or glutaredoxin levels are maintained in cancer cells, then the cells maintain resistance to chemotherapeutic agents, but the anti-cancer effect is reduced
Solution Approach 1:
The patent applies parameter changes by modifying the redox state parameters of cancer cells through dithio-containing compound administration. These compounds alter the glutathione redox couple ratio and deplete reduced glutathione levels, thereby changing the biochemical parameters that confer resistance. This parameter modification sensitizes the cancer cells to chemotherapeutic agents, restoring their effectiveness without increasing the drug dosage
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 compounds increase patient survival time by sensitizing cancer cells to chemotherapy, overcoming resistance and enhancing anti-cancer effects, as demonstrated in clinical trials for non-small cell lung carcinoma and adenocarcinoma patients.
Implementation Method 1
Administration of oxidative metabolism-affecting compounds, such as the disodium salt of 2,2′-dithio-bis-ethane sulfonate (Tavocept™), which modulate thioredoxin and glutaredoxin pathways
Data Source
AI summary
The present invention discloses and claims compositions, methods of treatment, and kits which cause an increase in the time of survival in cancer patients, wherein the cancer: (i) overexpresses thioredoxin or glutaredoxin and/or (ii) exhibits evidence of thioredoxin- or glutaredoxin-mediated resistance to one or more chemotherapeutic interventions. The present invention also discloses and claims methods and kits for the administration of said compositions to properly treat cancer patients. Additionally, the present invention discloses and claims methods and kits for quantitatively determining the level of expression of thioredoxin or glutaredoxin in the cancer cells of a cancer patient, methods of using those determined levels in the initial diagnosis and/or planning of subsequent treatment methodologies for said cancer patient, as well as ascertaining the potential growth “aggressiveness” of the particular cancer and treatment responsiveness of the particular type of cancer. Further, the present invention discloses and claims novel pharmaceutical compositions, methods, and kits used for the treatment of patients with medical conditions and disease where there is the overexpression of thioredoxin and/or glutaredoxin, and wherein this overexpression is associated with deleterious physiological effects in the patients.