Tinostamustine Combination Therapy for Drug-Resistant TNBC

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Solution Overview

Problem

Current treatments for triple negative breast cancer (TNBC) are ineffective due to drug resistance and the aggressive nature of the disease, leading to high recurrence and metastasis rates, with limited therapeutic options available, particularly for BRCA-1 wildtype and basal-like 1 (BL1) subtypes.

Innovation Solution

Tinostamustine or its pharmaceutically acceptable salts are used as a monotherapy or in combination with DNA repair inhibitors like PARP inhibitors (e.g., olaparib) to treat TNBC, particularly targeting BRCA-1 wildtype and basal-like 1 (BL1) subtypes, offering a novel chemotherapeutic approach.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional chemotherapy treatments are used for TNBC, then treatment options are available, but drug resistance develops leading to treatment failure

Engineering Contradiction:

Improvetreatment effectivenessVSAvoiddrug resistance

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent modifies the chemical structure of tamoxifen by introducing a specific side chain (formula I) to create tinostamustine, changing the pharmacological parameters to achieve enhanced efficacy against TNBC while overcoming drug resistance mechanisms

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The invention combines tamoxifen core structure with a specific side chain containing HDAC inhibition activity, creating a composite molecule that simultaneously provides anti-proliferative and epigenetic modulation effects to overcome resistance

Inventive Principle:

Principle #40Composite materials

2Productivity

If surgery is used to remove tumours, then local cancer removal is achieved, but it cannot treat disseminated hematological cancers

Engineering Contradiction:

Improvetreatment coverageVSAvoidtreatment applicability

Core Design Contradiction:

ProductivityVSAdaptability or versatility

Solution Approach 1:

The patent replaces mechanical surgery with a chemical therapy approach using tinostamustine, which can penetrate and treat cancers throughout the body including hematological cancers, replacing the mechanical limitation of surgery with systemic chemical action

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

3Reliability

If radiation therapy is used to treat cancer, then cancer cell death is achieved, but acute and temporary side effects occur

Engineering Contradiction:

Improvecancer cell killingVSAvoidacute side effects

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent uses tinostamustine as an intermediary chemical agent that mediates cancer cell death through targeted molecular mechanisms (HDAC inhibition and anti-proliferative effects) rather than direct physical radiation damage, reducing acute side effects while maintaining efficacy

Inventive Principle:

Principle #24Intermediary (Mediator)

Data Source

PatentUS20250275945A1Compounds for treating tnbc

Publication Date: 2025.09.04 PURDUE PHARMA LP

AI summary

There is provided tinostamustine or a pharmaceutically acceptable salt thereof for use in the treatment of triple negative breast cancer (TNBC) to a patient in need thereof.