MYC Amplification and TEAD Blockade for Pan-RAS Resistance

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Solution Overview

Problem

Resistance to broad-spectrum RAS inhibitors, such as RMC-7977, occurs in tumors driven by RAS mutations, and the underlying mechanisms for overcoming this resistance are not well understood.

Innovation Solution

Identifying tumors resistant to RAS multi-inhibitor therapy by detecting elevated MYC and/or JUN copy numbers, and administering a combination of a RAS multi-inhibitor and a TEAD inhibitor to treat these resistant tumors.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If a RASMULTI inhibitor is used to treat RAS-mutated tumors, then initial treatment efficacy is achieved, but resistance develops over time

Engineering Contradiction:

Improvetreatment efficacyVSAvoidduration of response

Core Design Contradiction:

ReliabilityVSDuration of action of stationary object

Solution Approach 1:

The patent applies preliminary action by identifying MYC and JUN copy number status before initiating combination therapy. This allows selection of patients most likely to respond to the RASMULTI inhibitor plus TEAD inhibitor combination, preventing resistance before it develops. The preliminary identification of molecular markers enables proactive rather than reactive treatment strategy.

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent introduces TEAD inhibitor as an intermediary agent that blocks the compensatory MYC-JUN-TEAD signaling pathway activated in response to RAS inhibition. This intermediary pathway blockade prevents the development of resistance mechanisms, acting as a mediator between the primary RAS inhibitor and the tumor to prevent adaptive resistance.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Reliability

If combination therapy with RASMULTI inhibitor and TEAD inhibitor is administered, then resistance is overcome, but treatment complexity increases

Engineering Contradiction:

Improveovercoming resistanceVSAvoidtreatment regimen complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent applies parameter changes by using molecular copy number parameters (MYC and JUN) to determine treatment eligibility. This objective, quantifiable parameter system simplifies the decision-making process for combination therapy, transforming a complex clinical judgment into a clear biomarker-based selection criterion that guides treatment assignment.

Inventive Principle:

Principle #35Parameter changes

3Measurement precision

If MYC and JUN copy numbers are identified to select patients, then treatment precision is improved, but diagnostic complexity increases

Engineering Contradiction:

Improvepatient selection accuracyVSAvoiddiagnostic complexity

Core Design Contradiction:

Measurement precisionVSDifficulty of detecting and measuring

Solution Approach 1:

The patent applies segmentation by separating the diagnostic process into distinct, sequential steps: first assessing MYC copy number, then assessing JUN copy number, and finally integrating these results for treatment decision-making. This segmented approach to molecular characterization makes the complex diagnostic process more manageable and systematic.

Inventive Principle:

Principle #1Segmentation

Data Source

PatentUS20250250640A1MYC amplification drives resistance to pan-ras inhibitors in pancreatic cancer

Publication Date: 2025.08.07 REVOLUTION MEDICINES INC

AI summary

Methods of treating a tumor in a subject comprising administering to the subject an amount of a RASMULTI inhibitor and an amount of a TEAD inhibitor, effective to treat a tumor, and methods of treating a tumor resistant to a RASMULTI inhibitor therapy comprising administering to a tumor so-identified an amount of a RASMULTI inhibitor and an amount of a TEAD inhibitor, effective to treat a tumor resistant to a RASMULTI inhibitor therapy.