Selective GR Modulators for Neuroepithelial Tumor Burden Reduction
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Solution Overview
Problem
Conventional treatments for neuroepithelial tumors such as meningioma, schwannoma, and ependymoma, including surgery, radiation therapy, and chemotherapy, often result in severe side effects due to their non-selective nature, damaging healthy tissues and compromising patient health.
Innovation Solution
Administration of selective glucocorticoid receptor modulators (SGRMs), such as non-steroidal compounds like mifepristone or CORT125134, to reduce tumor load in GR+ neuroepithelial tumors, potentially combined with other therapies.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional treatments (surgery, radiation therapy, chemotherapy) are used to treat neuroepithelial tumors, then tumor cells are killed through generalized DNA damage and chromosomal destabilization, but severe side effects occur due to non-selective treatment of healthy tissues
Solution Approach 1:
The patent applies local quality by developing selective glucocorticoid receptor modulators that specifically target GR+ neuroepithelial tumors. The SGRMs exhibit selective binding affinity for glucocorticoid receptors expressed in tumor cells, enabling localized therapeutic action that spares healthy tissues. This selectivity is achieved through molecular design of compounds with specific binding characteristics that differentiate between tumor and normal cells.
Solution Approach 2:
The patent employs parameter changes by modifying the glucocorticoid receptor modulation approach from non-selective to selective. The SGRMs are designed with specific binding affinities and pharmacological parameters that enable selective activation of GR in tumor cells. The modulators exhibit controlled binding kinetics and affinity parameters that differentiate tumor cell response from healthy tissue effects.
2Productivity
If non-selective treatments are used to achieve broad cancer cell destruction, then tumor burden is reduced, but long-term patient health is compromised due to damage to normally healthy organs
Solution Approach 1:
The SGRMs achieve local quality by selectively targeting GR+ neuroepithelial tumors while preserving healthy tissues. The selective binding affinity and receptor-specific mechanism ensure that therapeutic effects are localized to tumor cells expressing glucocorticoid receptors, thereby reducing tumor burden without compromising long-term patient health through widespread tissue damage.
3Object-affected harmful factors
If selective glucocorticoid receptor modulators are used to target GR+ neuroepithelial tumors, then side effects are reduced through selective targeting, but the mechanism relies on specific receptor expression in tumor cells
Solution Approach 1:
The patent uses an intermediary approach by targeting the glucocorticoid receptor as a mediator between the SGRM and tumor cell death. The GR serves as a selective marker and therapeutic target that mediates the effect of SGRMs specifically in GR+ neuroepithelial tumors. This intermediary strategy enables selective treatment while maintaining a clear mechanism of action through receptor-mediated signaling.
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
Reduces tumor burden with fewer side effects by selectively targeting glucocorticoid receptors, offering a novel therapeutic option for neuroepithelial tumors like meningioma, schwannoma, and ependymoma.
Implementation Method 1
Administration of selective glucocorticoid receptor modulators (SGRMs), such as non-steroidal compounds like mifepristone or CORT125134, to reduce tumor load in GR+ neuroepithelial tumors
Data Source
AI summary
Applicant discloses methods for treating a glucocorticoid receptor positive (GR+) neuroepithelial tumor in a subject, comprising administering a selective glucocorticoid receptor modulator (SGRM) in an amount effective to reduce the tumor load in a subject. The GR+ neuroepithelial tumor may be a neurofibromatosis type 2 (NF 2) tumor; the GR+ neuroepithelial tumor may be a schwannoma, meningioma, or ependymoma. In embodiments, the GR+ neuroepithelial tumor is not an adrenocorticotropic hormone (ACTH)-secreting tumor. In embodiments, the SGRM comprises a steroidal backbone. In embodiments, the SGRM is mifepristone. In embodiments, the SGRM comprises a non-steroidal backbone, such as, e.g., a cyclohexyl pyrimidine, a fused azadecalin, a heteroaryl ketone fused azadecalin, or an octahydro fused azadecalin backbone. The SGRM may be administered orally. The SGRM may be administered alone. In embodiments, the SGRM is administered with at least one non-SGRM therapy, e.g., a chemotherapy, a radiation therapy, or other therapeutic agents.