MetAP2 Inhibitor Biomarkers for Reversing Cancer Therapy Metabolic Dysfunction
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Solution Overview
Problem
Obese and metabolically dysfunctional cancer patients show resistance to traditional chemotherapy and immunotherapy treatments due to induced metabolic dysfunction, which is often exacerbated by cancer therapeutics, leading to hyperglycemia and immunosuppressive states that hinder treatment efficacy.
Innovation Solution
Administration of MetAP2 inhibitors in combination with other active agents to reduce the expression or amount of biomarkers such as IL-10, arginase-1, myeloid-derived suppressor cells (MDSC), regulatory T cells, leptin, PD-1, PD-L1, and CTLA-4, thereby modulating tumor microenvironments and improving treatment responsiveness.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If cancer therapeutics are administered to obese patients, then cancer treatment is provided, but metabolic dysfunction and hyperglycemia are induced which reduces treatment efficacy
Solution Approach 1:
The patent introduces MetAP2 inhibitors as intermediary substances that mediate between the cancer therapy and the metabolic dysfunction. These inhibitors specifically target and inhibit metap2 enzyme activity, which is responsible for converting L-asparaginase to its active form. By blocking this enzymatic conversion, the MetAP2 inhibitors prevent the harmful metabolic effects (hyperglycemia, immunosuppression) while allowing the cancer therapy to remain effective, thus resolving the contradiction between providing treatment and avoiding harmful metabolic side effects
Solution Approach 2:
The patent changes the biochemical parameter of metap2 enzyme activity by administering MetAP2 inhibitors. This parameter change prevents the enzymatic conversion of L-asparaginase to its active form, thereby altering the metabolic pathway that would otherwise lead to hyperglycemia and immunosuppression. This parameter intervention allows the cancer therapy to proceed without inducing harmful metabolic effects
2Reliability
If MetAP2 inhibitors are administered to suppress immunosuppressive factors, then treatment responsiveness is improved, but additional therapeutic agents are required
Solution Approach 1:
The patent demonstrates that MetAP2 inhibitors have multi-functional effects: they suppress multiple immunosuppressive factors (IL-10, arginase-1, MDSC, regulatory T cells, leptin, PD-1, PD-L1, CTLA-4) simultaneously and improve treatment responsiveness across different cancer types. This universal mechanism allows a single agent to address multiple barriers to therapy effectiveness, reducing the need for multiple separate therapeutic agents and simplifying the overall treatment regimen
Data Source
AI summary
The present disclosure relates to modified or polymer conjugated MetAP2 inhibitors. The present disclosure also relates to methods of treating, or ameliorating at least one symptom of, metabolic dysfunction associated with a treatment in a subject having cancer. The present disclosure also relates to methods of treating, or ameliorating at least one symptom of, cancer comprising administering a combination of a polymer conjugated MetAP2 inhibitors and at least one second agent.