SUMO Pathway Targeting for Broad Brain Cancer Therapy
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Solution Overview
Problem
Current strategies for treating brain cancers, such as glioblastoma multiforme, are ineffective due to the lack of targeted proteins or pathways that can inhibit the progression and proliferation of all types and subtypes of brain cancer cells, despite elevated expression or activity of proteins like EGFR in 40-60% of GBM samples.
Innovation Solution
Targeting the SUMO conjugation pathway by administering agents that decrease the levels of SUMO conjugated proteins, either through inhibitors of the SUMO conjugation pathway or activators of SUMO deconjugation enzymes, in combination with chemotherapy or radiation therapy to inhibit cancer cell proliferation, survival, and DNA synthesis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current treatment strategies (surgical resection with radio- and chemotherapy) are used for glioblastoma, then some cancer cells are treated, but the treatment is ineffective due to lack of targeted pathways that can inhibit progression and proliferation of all types and subtypes of brain cancer cells
Solution Approach 1:
The patent targets the SUMO conjugation pathway as a universal therapeutic target that is active across all types and subtypes of brain cancer cells, including glioblastoma, astrocytomas, and oligodendrogliomas. By inhibiting this common pathway rather than type-specific markers, the treatment achieves broad versatility while maintaining reliability through focused pathway inhibition
Solution Approach 2:
The patent uses SUMO conjugation pathway components (such as E1 activating enzyme, E2 conjugating enzyme Ubc9, or SENP deconjugating enzymes) as intermediary targets. These intermediaries are central to the cancer progression process and can be inhibited to block multiple downstream oncogenic pathways simultaneously, improving both treatment effectiveness and broad applicability
2Quantity of substance
If targeted proteins like EGFR are used for treatment, then some cancer cells with elevated EGFR expression are treated, but treatment fails because not all brain cancer subtypes show elevated EGFR expression
Solution Approach 1:
The patent identifies the SUMO conjugation pathway as a universal target present and active in all brain cancer subtypes, unlike EGFR which is only elevated in 40-60% of GBM samples. This ensures that a higher quantity of cancer cells (approaching 100%) are responsive to treatment while maintaining reliability through consistent pathway inhibition across all cell types
3Reliability
If SUMO conjugation pathway is targeted to inhibit cancer cell proliferation and survival, then cancer progression is blocked, but the complexity of the conjugation process with multiple enzymes (E1, E2, SENPs) makes target selection difficult
Solution Approach 1:
The patent segments the SUMO conjugation pathway into distinct enzymatic components (E1 activating enzyme, E2 conjugating enzyme Ubc9, E3 ligases, and SENP deconjugating enzymes) and identifies specific components as therapeutic targets. This segmentation allows selection of single-point targets within the complex pathway, simplifying drug development while maintaining reliable cancer inhibition through focused pathway disruption
Data Source
AI summary
Disclosed herein are methods relating to inhibiting or reducing proliferation of a cancer cell, for treating cancer in a subject in need of treatment, predicting the risk of progression of cancer to a more aggressive cancer, and screening for cancer in a subject, that comprise detecting and/or decreasing the levels of SUMO conjugated proteins and detecting and/or interfering with SUMO conjugation.