HER2 Targeting Agents in Non-Amplified Cancer Stem Cells

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Current treatments for breast cancer that target the HER2 pathway are limited to cancers with HER2 amplification, and there is a need for effective therapies for non-HER2-amplified cancers, particularly those with cancer stem cells expressing HER2, as these cells drive tumor growth and resistance to traditional therapies.

Innovation Solution

The use of HER2 targeting agents, such as trastuzumab, in combination with IL6R targeting agents like Tocilizumab and Akt inhibitors like perifosine, to treat non-HER2-amplified cancers by targeting cancer stem cells expressing HER2, and preventing resistance through the inhibition of the IL6 inflammatory loop.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If HER2 targeting agents are used to treat breast cancer, then treatment efficacy is improved for HER2-amplified cancers, but the treatment is ineffective for non-HER2-amplified cancers

Engineering Contradiction:

Improvetreatment efficacyVSAvoidapplicability to different cancer types

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent applies local quality by targeting HER2 expression specifically in cancer stem cells rather than requiring HER2 amplification in the entire tumor. This allows selective treatment of the HER2-expressing stem cell population within non-HER2-amplified tumors, expanding treatment applicability while maintaining efficacy

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The patent changes the diagnostic parameter from HER2 amplification status to HER2 expression status in cancer stem cells. This parameter shift enables identification of a new patient population (non-HER2-amplified but HER2-expressing stem cells) who can benefit from HER2-targeted therapy

Inventive Principle:

Principle #35Parameter changes

2Reliability

If traditional therapies are used to treat cancer, then tumor growth is controlled, but resistance develops due to cancer stem cells

Engineering Contradiction:

Improvetumor growth controlVSAvoidtreatment durability

Core Design Contradiction:

ReliabilityVSDuration of action of stationary object

Solution Approach 1:

The patent applies preliminary action by targeting cancer stem cells with HER2-targeted therapy before they can develop resistance to traditional therapies. By eliminating or controlling the stem cell population upfront, the treatment prevents future resistance development and extends treatment durability

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent employs feedback by monitoring HER2 expression in cancer stem cells to guide treatment decisions. This feedback mechanism allows adjustment of therapy to maintain effectiveness against the evolving stem cell population, preventing resistance

Inventive Principle:

Principle #23Feedback

Data Source

PatentUS9327023B2HER2 targeting agent treatment in non-HER2-amplified cancers having HER2 expressing cancer stem cells

Publication Date: 2016.05.03 THE RGT UNIV OF MICHIGAN

AI summary

The present invention relates to compositions, methods, and kits for treating cancers with HER2 targeting agents and preventing resistance thereto. In particular embodiments, non-HER2-amplified cancers are treated with HER2 targeting agents, wherein the cancer stem cells in the cancer express HER2 and/or HER2 indicator marker. The present invention also relates to compositions, methods, and kits for detecting expression of HER2 and/or a HER2 indicator marker in non-HER2-amplified cancer samples from a subject, and identifying the subject as responsive to treatment with a HER2 targeting agent and/or treating the subject with a HER2 targeting agent.