Selective Glucocorticoid Receptor Antagonism for Cancer NLR Normalization

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Solution Overview

Problem

The neutrophil-to-lymphocyte ratio (NLR) in cancer patients is often elevated, indicating poorer prognosis and resistance to cancer treatments, with existing methods failing to effectively normalize this ratio and enhance treatment outcomes.

Innovation Solution

Administer a nonsteroidal glucocorticoid receptor antagonist, such as relacorilant, in combination with cancer treatments to reduce NLR in cancer patients, thereby normalizing the ratio and enhancing treatment efficacy.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional cancer treatments are administered, then cancer therapy is provided, but the neutrophil-to-lymphocyte ratio remains elevated indicating poor prognosis

Engineering Contradiction:

ImproveprognosisVSAvoidneutrophil-to-lymphocyte ratio

Core Design Contradiction:

ReliabilityVSQuantity of substance

Solution Approach 1:

The patent introduces a glucocorticoid receptor antagonist as an intermediary substance that mediates between the cancer treatment and the immune system. This antagonist blocks the glucocorticoid receptor, preventing cortisol from suppressing lymphocyte function and promoting neutrophil survival, thereby normalizing the NLR without interfering with the primary cancer therapy's effectiveness

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the pharmacological parameter by using a selective glucocorticoid receptor antagonist instead of conventional cytotoxic agents. This parameter change allows normalization of the NLR from elevated levels to within normal range (≤3), transforming the prognostic indicator while maintaining cancer treatment efficacy

Inventive Principle:

Principle #35Parameter changes

2Reliability

If glucocorticoid receptor agonists are used, then immune suppression is achieved, but the neutrophil-to-lymphocyte ratio increases indicating poor prognosis

Engineering Contradiction:

Improveimmune suppressionVSAvoidneutrophil-to-lymphocyte ratio

Core Design Contradiction:

ReliabilityVSQuantity of substance

Solution Approach 1:

The patent inverts the conventional approach by using a glucocorticoid receptor antagonist instead of an agonist. This inversion blocks the harmful effects of glucocorticoid excess, allowing lymphocyte function to improve and neutrophil counts to decrease, thereby normalizing the NLR while maintaining appropriate immune suppression for cancer treatment

Inventive Principle:

Principle #13The other way round (Inversion)

3Productivity

If the neutrophil-to-lymphocyte ratio is normalized, then treatment response improves, but additional therapy is required

Engineering Contradiction:

Improvetreatment responseVSAvoidtherapy regimen

Core Design Contradiction:

ProductivityVSDevice complexity

Solution Approach 1:

The patent merges the glucocorticoid receptor antagonist with the primary cancer treatment regimen into a single integrated therapy. This combination approach simultaneously achieves cancer cell killing and NLR normalization, improving treatment response without requiring separate sequential therapies and thereby reducing overall treatment complexity

Inventive Principle:

Principle #5Merging (Combining)

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

The administration of relacorilant effectively reduces elevated NLR in cancer patients, improving treatment response, reducing tumor load, and promoting tumor elimination, leading to better clinical outcomes and prolonged survival.

Implementation Method 1

Administration of a nonsteroidal selective glucocorticoid receptor antagonist (GRA), such as relacorilant, in combination with a cancer treatment is effective to normalize (reduce) a neutrophil-to-lymphocyte ratio (NLR) in a cancer patient

Methodology Applied

Scientific EffectReceptor antagonism:

Data Source

PatentUS12440487B2Method of normalizing the neutrophil to lymphocyte ratio in cancer patients with a selective glucocorticoid receptor antagonist

Publication Date: 2025.10.14 CORCEPT THERAPEUTICS INC

AI summary

Methods for treating a cancer patient with a neutrophil-to-lymphocyte ratio (NLR) greater than 3 are disclosed, comprising administering a nonsteroidal glucocorticoid receptor antagonist (GRA) to such a cancer patient, effective to reduce the patient's NLR. The methods include administering a nonsteroidal GRA and a cancer treatment to such a cancer patient, effective to reduce the patient's NLR and enhance the treatment of the cancer patient. The GRA may be orally administered. The nonsteroidal GRA may be a nonsteroidal compound comprising a heteroaryl ketone fused azadecalin structure (e.g., relacorilant) or an octahydro fused azadecalin structure (e.g., exicorilant). The cancer treatment may include chemotherapy, immunotherapy, radiation therapy, administration of an anti-angiogenic agent, administration of a growth factor inhibitor, and surgery. The methods may enhance the cancer treatment, improve the prognosis of the cancer patient, improve the survival of the cancer patient, and provide beneficial clinical effects and advantages to the patient.