PI3K Combination Therapy to Suppress Insulin Feedback Reactivation

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Solution Overview

Problem

Existing therapies targeting the insulin-receptor/PI3K/AKT/mTOR pathway have struggled to identify effective compositions and methods for treating diseases or disorders associated with PI3K signaling, with PI3K inhibitors experiencing challenges such as hyperinsulinemia that re-activate the pathway, compromising their effectiveness.

Innovation Solution

Administering a modulator of glucose metabolism, such as a glucose-uptake inhibitor or a ketogenic diet, in combination with a pathway inhibitor, to modulate insulin levels and enhance the efficacy of PI3K pathway inhibitors.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If a PI3K inhibitor is administered to treat diseases associated with PI3K signaling, then the effectiveness of pathway inhibition is improved, but hyperinsulinemia occurs that re-activates the pathway and compromises treatment effectiveness

Engineering Contradiction:

Improveeffectiveness of pathway inhibitionVSAvoidhyperinsulinemia-induced pathway re-activation

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent applies preliminary anti-action by administering a modulator of glucose metabolism before or concurrent with the PI3K inhibitor to prevent hyperinsulinemia from occurring. This preemptive approach blocks the feedback mechanism that would otherwise re-activate the PI3K pathway, thereby maintaining reliable pathway inhibition throughout treatment.

Inventive Principle:

Principle #9Preliminary anti-action

Solution Approach 2:

The patent converts the harmful effect of hyperinsulinemia into a beneficial outcome by using the insulin feedback mechanism as a biomarker. The modulator of glucose metabolism transforms this previously harmful feedback into a useful indicator that can be monitored to assess treatment response and adjust therapy accordingly.

Inventive Principle:

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

2Reliability

If a modulator of glucose metabolism is added to the treatment regimen to reduce insulin feedback, then the effectiveness of PI3K inhibitors is enhanced, but the treatment complexity increases

Engineering Contradiction:

Improveeffectiveness of PI3K inhibitor treatmentVSAvoidtreatment regimen complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent applies universality by selecting modulators of glucose metabolism that serve multiple functions: they reduce insulin feedback to enhance PI3K inhibitor effectiveness, while also addressing metabolic side effects and improving overall patient metabolic health. This multi-functionality justifies the added treatment component by providing multiple benefits from a single intervention.

Inventive Principle:

Principle #6Universality (Multi-functionality)

3Reliability

If the dosage of PI3K inhibitor is increased to overcome pathway re-activation, then the pathway inhibition effectiveness is improved, but the side effects increase

Engineering Contradiction:

Improvepathway inhibition effectivenessVSAvoidtreatment side effects

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies feedback by implementing a monitoring system that tracks insulin levels and pathway activation status in response to treatment. Based on this feedback information, the treatment regimen can be adjusted to maintain effective pathway inhibition while avoiding excessive dosing that would increase side effects. The modulator of glucose metabolism provides continuous feedback control of the insulin pathway.

Inventive Principle:

Principle #23Feedback

Data Source

PatentUS20260014164A1Combination therapy for PI3k-associated disease or disorder

Publication Date: 2026.01.15 CORNELL UNIVERSITY

AI summary

Described herein are compositions and methods for treating a disease or disorder associated with PI3K signaling. For example, such compositions can include use of modulators of glucose metabolism, use of at least one kinase in the insulin-receptor/PI3K/AKT/mTOR pathway, and/or use of diet that influences the subject's metabolic state.