Glioblastoma Animal Model Targeting Tumor Stem Cells

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Solution Overview

Problem

Current methods for treating glioblastoma are inadequate due to high resistance to radiotherapy and chemotherapy, and there is a lack of effective therapeutic agents that can target the brain tumor's origin, making early diagnosis and treatment challenging.

Innovation Solution

A method is developed to predict the tissue origin of brain tumors by measuring allele frequencies of specific mutations in the subventricular zone (SVZ) and brain tumor tissue, using genes such as TERT, EGFR, p53, Pten, and Rb1, to determine the effective treatment target site and screen therapeutic agents.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If radiotherapy and chemotherapy are performed to treat glioblastoma, then tumor growth can be controlled to some extent, but treatment effectiveness is limited due to high resistance and tumor recurrence

Engineering Contradiction:
Improvetreatment effectivenessVSAvoiddrug resistance
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies preliminary action by identifying and targeting tumor stem cells before they cause recurrence. The therapeutic agent is designed to specifically recognize and eliminate tumor stem cells expressing CD133 and Nestin markers, preventing future tumor regrowth before it happens. This proactive approach addresses the root cause of recurrence rather than just treating visible tumor mass.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent applies local quality by creating a therapeutic agent with highly specific targeting capabilities. The agent selectively binds to tumor stem cells based on their unique surface markers (CD133 and Nestin), delivering treatment precisely to the resistant tumor stem cell population while sparing normal cells. This localized specificity overcomes the general resistance problem affecting conventional chemotherapy.

Inventive Principle:
Principle #3Local quality

2Productivity

If conventional therapeutic agents are used, then general tumor mass can be reduced, but they cannot effectively target tumor stem cells leading to recurrence

Engineering Contradiction:
Improvetumor reduction efficiencyVSAvoidtumor origin information
Core Design Contradiction:
ProductivityVSLoss of information

Solution Approach 1:

The patent applies the color changes principle by using fluorescent markers to visually identify and track tumor stem cells. The therapeutic agent incorporates fluorescent tags that allow researchers to observe the distribution and elimination of tumor stem cells in real-time, providing visual feedback on treatment effectiveness and helping to understand tumor origin and progression dynamics.

Inventive Principle:
Principle #32Color changes

Solution Approach 2:

The patent uses fluorescent markers and imaging techniques as intermediaries to bridge the gap between treating tumor mass and eliminating tumor stem cells. These visual intermediaries allow researchers to indirectly observe and verify the destruction of tumor stem cells that would otherwise be invisible, providing information about tumor origin and treatment impact without directly measuring stem cell destruction.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Speed

If the focus is on treating visible tumor mass, then immediate tumor burden is reduced, but the underlying tumor stem cells remain causing eventual recurrence

Engineering Contradiction:
Improvetumor response speedVSAvoidpatient survival time
Core Design Contradiction:
SpeedVSDuration of action of stationary object

Solution Approach 1:

The patent applies preliminary action by designing a therapeutic agent that proactively targets and eliminates tumor stem cells before they can regenerate the tumor. By focusing on the stem cell population from the outset rather than waiting for recurrence, the treatment achieves both rapid initial response and long-term durability, extending patient survival by preventing the root cause of recurrence.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent applies continuity of useful action by creating a therapeutic mechanism that continuously eliminates tumor stem cells throughout the treatment period. The agent maintains sustained activity against the stem cell population, ensuring continuous suppression of tumor regrowth capability rather than providing only temporary mass reduction, thereby extending the duration of therapeutic benefit and patient survival.

Inventive Principle:
Principle #20Continuity of useful action

Data Source

PatentUS20230232794A1Animal model of brain tumor and manufacturing method of animal model
Publication Date: 2023.07.27 KOREA ADVANCED INST OF SCI & TECH
  • US20230232794A1 patent drawing
  • US20230232794A1 patent drawing
  • US20230232794A1 patent drawing

AI summary

The present invention relates to a brain tumor animal model that directly reflects the phenomenon in a human patient and a method of preparing the same, and more specifically, a brain tumor animal model that mutations are introduced into p53, Pten, and EGFR genes, a screening method of a therapeutic agent for a brain tumor using the animal model, and a preparing method thereof.