Intermittent BRAF Kinase Inhibitor Dosing to Suppress Resistance

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Solution Overview

Problem

Cancer cells often develop resistance to BRAF inhibitors, leading to short-lived tumor responses as resistant cells adapt and become dependent on the drug for growth, making continuous dosing ineffective in maintaining treatment efficacy.

Innovation Solution

Administering BRAF kinase inhibitors on an intermittent dosing schedule, such as 4 weeks of treatment followed by 2 weeks without treatment, to delay or prevent the onset of resistance by creating a selective disadvantage for resistant cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If BRAF kinase inhibitors are administered continuously, then initial tumor response is achieved, but resistance develops rapidly making treatment ineffective

Engineering Contradiction:

Improvetreatment effectivenessVSAvoidduration of tumor response

Core Design Contradiction:

ReliabilityVSDuration of action of moving object

Solution Approach 1:

The patent applies periodic action by administering BRAF kinase inhibitors in cycles (e.g., 3 weeks on, 1 week off) rather than continuously. This periodic dosing schedule exploits the selective disadvantage of resistant cells during drug-free intervals, preventing them from becoming dominant and maintaining long-term treatment effectiveness.

Inventive Principle:

Principle #19Periodic action

2Adaptability or versatility

If resistant cells are exposed to continuous drug pressure, then they adapt and become dependent on the drug, but this makes them less fit without the drug

Engineering Contradiction:

Improveresistant cell adaptationVSAvoidcell fitness without drug

Core Design Contradiction:

Adaptability or versatilityVSReliability

Solution Approach 1:

The patent applies preliminary anti-action by introducing drug-free intervals before resistant cells can fully adapt and dominate the tumor population. During these intervals, resistant cells experience selective disadvantage and reduced fitness, preventing them from establishing complete drug dependence before the next treatment cycle begins.

Inventive Principle:

Principle #9Preliminary anti-action

Data Source

PatentUS11007194B2Method of treating a proliferative disease

Publication Date: 2021.05.18 ARRAY BIOPHARMA INC

AI summary

The present invention relates to a method of treating a patient with a serine/threonine kinase inhibitor wherein resistance to the treatment with a serine/threonine kinase inhibitor is suppressed by administering the serine/threonine kinase inhibitor on an intermittent dosing schedule.