Embelin Selective Targeting of Polyploid Tumor Cells

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Solution Overview

Problem

Current cancer treatments lack an effective method to selectively target and eliminate polyploid cancer cells, which can develop resistance to anti-cancer drugs and contribute to tumor recurrence through endoreplication and depolyploidization, leading to aggressive cancer forms.

Innovation Solution

A cell-based screening system exploiting Bcl-2 to protect polyploid cells from apoptosis and autophagic death, using the natural product embelin from Embelia ribes Burm to selectively kill polyploid cells, identified through conversion of diploid cell lines into polyploid populations and screening natural product extracts.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional anti-cancer treatments are used, then diploid cancer cells are targeted, but polyploid cancer cells develop resistance and survive

Engineering Contradiction:

Improveefficacy of anti-cancer treatmentVSAvoidresistance of polyploid cells

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies local quality by designing a treatment approach that specifically targets polyploid cells with different properties (elevated genomic content, impaired p53 function) rather than treating all cancer cells uniformly. The treatment exploits the unique vulnerability of polyploid cells to mitotic catastrophe while sparing diploid cells, achieving selective elimination based on local cellular characteristics.

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The patent utilizes parameter changes by inducing polyploidy in cancer cells through various treatments (chemotherapy, radiation, targeted therapy), which fundamentally alters the cellular state. This parameter change (from diploid to polyploid) creates a distinct vulnerability that can be exploited for selective killing, transforming the cellular state to enable targeted elimination.

Inventive Principle:

Principle #35Parameter changes

2Adaptability or versatility

If polyploid cells undergo endoreplication and depolyploidization, then tumor evolution and therapy resistance are facilitated, but no effective treatment selectively targets these cells

Engineering Contradiction:

Improvetumor evolution capabilityVSAvoidavailability of selective treatment

Core Design Contradiction:

Adaptability or versatilityVSEase of manufacture

Solution Approach 1:

The patent applies preliminary action by first inducing polyploidy in cancer cells through standard anti-cancer treatments, chemotherapy, or radiation therapy. This preliminary polyploidization creates a vulnerable state that can then be exploited by subsequent treatments designed to specifically kill polyploid cells, preventing their ability to undergo further endoreplication and depolyploidization cycles.

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent converts the harmful effect of polyploidy (which normally confers resistance and enables tumor evolution) into a beneficial target for selective elimination. By exploiting the unique characteristics of polyploid cells (impaired p53 function, genomic instability), the treatment transforms what was previously a survival mechanism into a vulnerability that can be specifically targeted and eliminated.

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

3Productivity

If standard cancer therapies are administered, then tumor cells are killed, but polyploid cells with impaired p53 function survive and cause recurrence

Engineering Contradiction:

Improvetumor cell killing efficiencyVSAvoidprevention of tumor recurrence

Core Design Contradiction:

ProductivityVSReliability

Solution Approach 1:

The patent applies segmentation by dividing the cancer cell population into distinct groups based on ploidy status (diploid vs. polyploid). This segmentation allows for differentiated treatment strategies where standard therapies target diploid cells while specialized treatments target polyploid cells, preventing the latter from causing recurrence while maintaining overall treatment efficiency.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent employs a composite treatment approach that combines standard anti-cancer therapies with polyploid-selective agents. This composite strategy layers multiple treatment mechanisms together - first using conventional therapies to kill diploid cells and induce polyploidy, then applying polyploid-specific treatments to eliminate surviving polyploid cells, creating a multi-layered defense against tumor recurrence.

Inventive Principle:

Principle #40Composite materials

Data Source

PatentUS11104633B2Cancer treatment using compounds that selectively target polyploid cancer cells for disruption

Publication Date: 2021.08.31 CHENGDU ANTICANCER BIOSCI LTD

AI summary

The disclosure provides a compound of Formula I:or a pharmaceutically acceptable salt thereof, wherein R1, R2, R3, and R4 are as described herein. The disclosure also provides methods for identifying a compound that selectively kills polyploid cells, and methods for killing polyploid tumor cells by administering a compound of Formula I to a patient in need thereof.