mTOR-Rictor Inhibitor Combination Therapy for Cancer Resistance
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Solution Overview
Problem
Current cancer treatment methods, particularly for small cell lung cancer, are inadequate and often lead to drug resistance, necessitating the development of new therapeutic approaches that can effectively target cancer cells with reduced toxicity and increased efficacy.
Innovation Solution
A composition comprising a compound of Formula I, which is an mTOR-Rictor complex inhibitor, Serine 473 phosphorylation inhibitor, or AKT2 inhibitor, used in combination with anti-cancer agents like cisplatin, rapamycin, or temsirolimus, to achieve a synergistic therapeutic effect and prevent resistance, thereby treating various types of cancer including small cell lung cancer with reduced overall toxicity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current cancer treatment methods (surgery, radiation, chemotherapy) are used for small cell lung cancer, then cancer cells can be treated, but drug resistance develops and treatment efficacy decreases
Solution Approach 1:
The patent segments the cancer treatment approach by using combination therapy with multiple compounds having different mechanisms of action. Specifically, it combines thiosemicarbazone derivatives (which inhibit topoisomerase II and generate reactive oxygen species) with other anti-cancer agents, thereby dividing the therapeutic effect into multiple independent pathways that can overcome drug resistance through their distinct mechanisms.
Solution Approach 2:
The patent creates a composite therapeutic regimen by combining multiple anti-cancer compounds with different mechanisms of action. The combination includes thiosemicarbazone derivatives along with other agents such as taxanes, platinum compounds, or molecularly targeted therapies, forming a composite treatment approach that addresses both current tumor burden and prevents future resistance development.
2Reliability
If higher doses of anti-cancer agents are administered to improve treatment efficacy, then cancer treatment effectiveness increases, but overall toxicity increases
Solution Approach 1:
The patent merges multiple anti-cancer compounds with different mechanisms of action into a single combination regimen. This allows each compound to be administered at lower, less toxic doses while collectively achieving the therapeutic effect of higher single-agent doses. The thiosemicarbazone derivative works synergistically with other agents, enabling dose reduction and toxicity minimization.
Solution Approach 2:
The thiosemicarbazone derivative acts as an intermediary agent that enhances the efficacy of other anti-cancer agents while allowing their doses to be reduced. Its multiple mechanisms of action (topoisomerase II inhibition, reactive oxygen species generation, cell cycle disruption) create a bridging effect that amplifies the therapeutic impact of co-administered drugs at lower concentrations.
Data Source
AI summary
A synergistically effective combination of an anti-cancer agent and a therapeutic compound, such as an mTOR-Rictor complex inhibitor, a Serine 473 phosphorylation inhibitor, an AKT2 inhibitor, or a combination thereof, for use in the treatment of cancer, and methods and uses thereof. Also included are methods and uses of a thiosemicarbazone for treating a cancer in a mammal in need thereof characterized by over-expression of RAS, by an EGFR mutation, and/or by over-expression of AKT2.