Stelliferin Compound Niche Suppression Leukemic Stem Cell Recurrence

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Solution Overview

Problem

Current antitumor agents are ineffective against leukemic stem cells that reside in a niche environment, leading to high recurrence rates of leukemia as these cells are resistant to drugs and survive in a resting stage, making it challenging to completely treat malignant tumors.

Innovation Solution

An extract derived from marine organisms, specifically Porifera, containing a Stelliferin compound is isolated and purified, which inhibits the niche formation of leukemic stem cells, enhancing the effectiveness of antitumor agents by targeting and suppressing the niche environment, thereby preventing tumor recurrence.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional antitumor agents are used to treat leukemia, then the activity and growth of malignant tumor cells are suppressed, but leukemic stem cells survive in a niche environment and cause high recurrence rates

Engineering Contradiction:
Improvetreatment effectivenessVSAvoiddrug resistance of leukemic stem cells
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The invention extracts and targets the niche environment where leukemic stem cells reside by using Stelliferin compounds to suppress niche formation. This separates the treatment approach from directly attacking the stem cells themselves, instead removing their protective habitat, thereby overcoming drug resistance.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The Stelliferin compound is administered before or alongside conventional antitumor agents to preemptively suppress niche formation. This preliminary action prevents leukemic stem cells from establishing their resistant state, making them vulnerable to subsequent chemotherapy treatments.

Inventive Principle:
Principle #10Preliminary action

2Productivity

If antitumor agents are administered to suppress malignant tumor cell growth, then tumor symptoms are remitted, but leukemic stem cells remain in a resting stage and activate later causing recurrence

Engineering Contradiction:
Improvetreatment speedVSAvoidtime to recurrence
Core Design Contradiction:
ProductivityVSLoss of time

Solution Approach 1:

By administering Stelliferin compounds to suppress niche formation before leukemic stem cells can activate and cause recurrence, the invention extends the remission period. This preliminary suppression of niche formation creates a longer window where the disease remains controlled.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The Stelliferin compound acts as an intermediary that targets the niche environment rather than directly attacking rapidly dividing tumor cells. This indirect approach allows it to affect slow-cycling or resting leukemic stem cells that conventional chemotherapy misses, thereby delaying recurrence.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Reliability

If a drug targeting niche formation is used in combination with antitumor agents, then complete treatment of leukemia may be achieved, but the complexity of the treatment regimen increases

Engineering Contradiction:
Improvecomplete treatment efficacyVSAvoidtreatment regimen complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The invention combines Stelliferin compounds with conventional antitumor agents into an integrated treatment regimen. This merging of niche suppression therapy with traditional chemotherapy creates a synergistic effect that targets both the niche environment and actively dividing tumor cells, achieving more complete treatment.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The Stelliferin compound serves multiple functions: it suppresses niche formation, sensitizes leukemic stem cells to chemotherapy, and potentially has direct antiproliferative effects. This multi-functionality allows a single agent to address multiple aspects of the disease, reducing the need for additional specialized treatments.

Inventive Principle:
Principle #6Universality (Multi-functionality)

Data Source

PatentEP3403661B1Marine organism-derived extract, compound, and medical composition having niche formation suppressing activity of leukemic stem cells
Publication Date: 2021.07.28 YAKULT HONSHA KK
  • EP3403661B1 patent drawingFigure 1A
  • EP3403661B1 patent drawingFigure 1B
  • EP3403661B1 patent drawingFigure 2A

AI summary

Using the cobblestone area (CA) formation inhibitory activity of human leukemic stem cell-like cells as an indicator, a fraction having the activity has been extracted from the fat-soluble fraction of Porifera, then, a compound having the activity has been isolated and purified from the aforementioned fraction, and then, the structure thereof has been determined, so that a Stelliferin compound comprising a novel compound has been identified. Moreover, it has been found that the isolated and purified Stelliferin compound significantly suppresses the niche formation of leukemic stem cell-like cells derived from human chronic myelogenous leukemia (CML) having resistance to existing antitumor agents and enhances the effects of antitumor agents on the cells. The present invention provides a pharmaceutical composition having inhibitory or suppressive activity against the niche formation of leukemic stem cells, a prophylactic agent against the recurrence of malignant tumor, which involves the combined use of other antitumor drugs, and the like.