MAT2A and Type I PRMT Inhibitor Combination Therapy
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Solution Overview
Problem
Current cancer therapies, such as chemotherapy and immunotherapy, have cytotoxic effects that are not restricted to cancer cells, leading to adverse side effects in normal tissues, and there is a need for more effective treatments for cancer, particularly targeting dysregulated pathways involving methionine adenosyltransferase II alpha (MAT2A) and Type I protein arginine methyltransferase (PRMT) in various cancers.
Innovation Solution
A combination product comprising a methionine adenosyltransferase II alpha (MAT2A) inhibitor and a Type I protein arginine methyltransferase (PRMT) inhibitor is administered to treat cancer, specifically targeting MAT2A-associated and PRMT-associated diseases, including those characterized by reduced MTAP gene expression or function.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If chemotherapy and immunotherapy are used to treat cancer, then cancer cells can be killed, but adverse side effects occur in normal tissues due to non-selective cytotoxic effects
Solution Approach 1:
The patent segments the therapeutic approach by using two distinct inhibitors targeting different but related pathways: a MAT2A inhibitor that blocks SAM production and a Type I PRMT inhibitor that blocks arginine methylation. This segmentation allows for more selective cancer cell targeting while sparing normal tissues that have different metabolic dependencies
Solution Approach 2:
The patent exploits local quality differences between cancer and normal cells by targeting the upregulated MAT2A and Type I PRMT pathways specifically in cancer cells. Normal tissues with different metabolic profiles are less affected, reducing adverse side effects while maintaining cancer cell killing efficacy
2Reliability
If existing cancer therapies are used, then some treatment effect is achieved, but treatment effectiveness is insufficient for many cancer types
Solution Approach 1:
The patent merges two inhibitor therapies into a combination treatment: a MAT2A inhibitor that depletes SAM and a Type I PRMT inhibitor that blocks methylation. This combination produces synergistic effects that more effectively inhibit cancer cell proliferation than either agent alone, addressing the insufficient effectiveness of single-agent therapies
Solution Approach 2:
The combination therapy maintains continuous disruption of the methylation pathway by simultaneously blocking SAM production (MAT2A inhibition) and methylation activity (PRMT inhibition), preventing cancer cells from recovering or compensating through alternative pathways, thereby sustaining effective anti-proliferative pressure
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 therapy effectively treats cancer by inhibiting the proliferative capacity of cancer cells, offering a more targeted approach with potential synergistic effects that enhance treatment outcomes over existing therapies.
Implementation Method 1
The catalysis of methionine and ATP to form SAM by methionine adenosyltransferases is considered the rate-limiting step in this process
Implementation Method 2
Protein Arginine Methyltransferases (PRMTs) that transfer the methyl group from S-adenosyl-L-methionine (SAM) to the substrate arginine side chain producing S-adenosyl-homocysteine (SAH) and methylated arginine
Data Source
AI summary
Provided herein is a combination therapy and methods of using such combination therapy to treat diseases or disorders associated with MAT2A and/or Type I PRMT.