Glucocorticoid Receptor Modulator Gene Expression Profiling
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current methods lack effective ways to identify and treat cancer patients who would benefit from glucocorticoid receptor (GR) modulator-based therapies, as the relationship between GR expression and tumor progression is unclear, and existing treatments do not account for individual patient gene expression profiles.
Innovation Solution
Administering a glucocorticoid receptor modulator, such as relacorilant, in combination with a cancer chemotherapeutic agent, and measuring specific gene expression levels in patients to determine which individuals will benefit from this treatment approach, using a panel of genes like COX2, DUSP1, GSK3b, MCL-1, PIK3CG, RGS-2, SGK1, and STAT3 to personalize cancer therapy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If glucocorticoid receptor modulator is administered to all cancer patients, then some patients may benefit from treatment, but many patients will receive unnecessary treatment without benefit
Solution Approach 1:
The patent applies preliminary action by measuring gene expression levels (such as COX2, DUSP1, GSK3b, MCL-1, PIK3CG, RGS-2, SGK1, and STAT3) before administering the glucocorticoid receptor modulator. This preliminary measurement identifies patients who are likely to benefit from treatment, ensuring that the modulator is only given to those with the appropriate genetic profile. This prevents unnecessary treatment exposure while maintaining high treatment effectiveness for responsive patients.
2Productivity
If individualized treatment based on gene expression profiling is implemented, then treatment efficiency is improved, but treatment complexity and cost increase
Solution Approach 1:
The patent applies segmentation by dividing cancer patients into distinct subgroups based on their gene expression profiles. Specifically, patients are segmented into those who express GR at levels indicative of responsiveness to GR modulators and those who do not. This segmentation allows for streamlined treatment protocols where only the responsive subgroup receives the modulator, improving overall treatment efficiency while managing complexity through clear diagnostic criteria.
Solution Approach 2:
The patent uses gene expression levels as an intermediary biomarker to mediate between the patient's genetic profile and the treatment decision. By measuring specific genes (COX2, DUSP1, GSK3b, MCL-1, PIK3CG, RGS-2, SGK1, STAT3), the system translates complex genetic information into a simple yes/no indicator for treatment responsiveness, thereby simplifying the treatment protocol while maintaining high efficiency.
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
This approach allows for the identification of patients likely to benefit from combined GR modulator and chemotherapy treatment, improving treatment outcomes by ensuring appropriate therapy is administered to those who will derive benefit while avoiding unnecessary treatment for those who will not, thus enhancing cancer treatment efficiency and clinical trial effectiveness.
Implementation Method 1
GR action is triggered by binding of glucocorticoids (GC) to GR, forming complex comprising the GR and the GC, leading to activation of the GR, its translocation to the cell nucleus, and interaction of the complex with nuclear genetic material.
Implementation Method 2
The glucocorticoid receptor (GR) is a is a nuclear hormone receptor that controls the transcription of multiple genes.
Data Source
AI summary
Novel methods for treating cancer include: administering a glucocorticoid receptor modulator (GRM) to a patient, and determining whether or not the expression level of a gene is decreased in comparison with baseline levels of the gene measured in the patient prior to the GRM administration, thereby identifying a patient as being likely to benefit from cancer chemotherapy in conjunction with GRM administration where the expression level of a gene following GRM administration is decreased in comparison with corresponding gene baseline levels; and administering to said identified patient a combination of a GRM and cancer chemotherapy, whereby the cancer is treated in the patient.The GRM may be selected from relacorilant, CORT125281, CORT122928, and CORT113176. The cancer chemotherapy agent may be a taxane. The gene expression level measured may be selected from 50 identified genes, and may be selected from COX2, DUSP1, GSK3b, MCL-1, PIK3CG, RGS-2, SGK1, and STAT3.