Selective GR Modulators with Chemotherapy for Pancreatic Tumor Reduction

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Pancreatic cancer has a poor prognosis due to limited surgical resectability and severe side effects from conventional treatments like radiotherapy and chemotherapy, necessitating a more targeted therapeutic approach.

Innovation Solution

Administering a chemotherapeutic agent in combination with a glucocorticoid receptor modulator (GRM), particularly a selective glucocorticoid receptor modulator (SGRM), to reduce tumor load in non-ACTH-secreting pancreatic tumors.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional chemotherapy is used to treat pancreatic cancer, then tumor destruction is achieved, but severe side effects occur due to non-selective damage to healthy tissues

Engineering Contradiction:

Improvetumor destruction effectivenessVSAvoidside effects on healthy tissues

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent uses glucocorticoid receptor modulators as intermediary agents that selectively target cancer cells through the GR signaling pathway while sparing healthy tissues. These modulators act as mediators between the treatment goal and the cancer cells, providing selective toxicity without the broad damage caused by conventional chemotherapy

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention applies selective GR modulators that exhibit local quality differences between cancer and healthy cells. The treatment targets specific GR-mediated pathways that are dysregulated in pancreatic cancer, creating a localized therapeutic effect that spares normal tissues from damage

Inventive Principle:

Principle #3Local quality

2Power

If radiotherapy is used to deliver large doses of radiation locally, then tumor irradiation is effective, but patient survival rate remains very low

Engineering Contradiction:

Improveradiation dose deliveryVSAvoidpatient survival rate

Core Design Contradiction:

PowerVSReliability

Solution Approach 1:

The patent combines GR modulator therapy with conventional treatments to create a synergistic effect. By merging selective pharmacological targeting with radiation or chemotherapy, the invention achieves improved patient outcomes that neither treatment could accomplish alone

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The invention changes the therapeutic parameter from non-selective cytotoxicity to selective GR pathway modulation. This parameter change allows for effective tumor treatment while maintaining patient health and improving survival rates through targeted intervention

Inventive Principle:

Principle #35Parameter changes

3Reliability

If glucocorticoid receptor signaling is activated to treat cancer, then apoptosis may be induced in some cancers, but it may also promote tumor growth in other contexts

Engineering Contradiction:

Improveapoptosis induction in cancer cellsVSAvoidpotential tumor growth promotion

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

Instead of activating GR signaling broadly, the patent inverts the approach by using selective GR modulators that can either activate or inhibit GR pathways depending on the specific cancer context. This inverted strategy allows for precise control over the therapeutic effect, preventing harmful tumor growth promotion while maintaining beneficial apoptosis induction

Inventive Principle:

Principle #13The other way round (Inversion)

Solution Approach 2:

The invention changes the parameter of GR signaling from constitutive activation to context-dependent modulation. By altering the signaling state based on specific cancer types and GR pathway dysregulation patterns, the treatment achieves reliable apoptosis induction without promoting tumor growth in contexts where activation would be harmful

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentUS12370175B2Glucocorticoid receptor modulators to treat pancreatic cancer

Publication Date: 2025.07.29 CORCEPT THERAPEUTICS INC

AI summary

Methods and compositions for treating a subject hosting a non-ACTH-secreting pancreatic tumor are disclosed. The methods include administering to the subject a chemotherapeutic agent and a glucocorticoid receptor modulator (GRM), preferably a selective glucocorticoid receptor modulator (SGRM), to reduce the tumor load in the subject. The non-ACTH-secreting pancreatic tumor may be an exocrine pancreatic tumor. The GRM may be a nonsteroidal GRM or a nonsteroidal SGRM. The nonsteroidal SGRM may be a nonsteroidal compound comprising: a fused azadecalin structure; a heteroaryl ketone fused azadecalin structure; or an octahydro fused azadecalin structure. Pharmaceutical compositions comprising a chemotherapeutic agent and a GRM are disclosed. The GRM in such pharmaceutical compositions may be a nonsteroidal GRM, and may be a nonsteroidal SGRM. The nonsteroidal SGRM may comprise: a fused azadecalin structure; a heteroaryl ketone fused azadecalin structure; or an octahydro fused azadecalin structure.