PPARG Inverse-Agonists for Targeted Cancer Therapy
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Solution Overview
Problem
Current treatments for PPARG activated cancers, such as breast, esophageal, pancreatic, colorectal, hepatocellular, and bladder cancers, lack targeted therapeutics, leading to poor prognosis and limited treatment options for invasive forms of these diseases.
Innovation Solution
Development of PPARG signaling modulators, specifically inverse-agonists like T0070907 and SR10221, that downregulate PPARG signaling by targeting mutations in PPARG and RXRA, reducing cellular proliferation associated with these cancers, and potential use of CRISPR/Cas systems for gene editing to correct mutations.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional chemotherapy regimens are used for invasive PPARG activated cancers, then treatment coverage is provided, but treatment effectiveness is limited due to lack of targeted therapeutics
Solution Approach 1:
The patent applies parameter changes by developing inverse-agonists that specifically target and reverse the up-regulated PPARG signaling pathway in PPARG-activated cancers. These compounds change the molecular parameter of PPARG receptor activity from activated to inhibited state, providing targeted therapy that addresses the specific molecular characteristic of these cancers while improving treatment effectiveness beyond conventional chemotherapy
Solution Approach 2:
The patent segments the cancer treatment approach by identifying and targeting the specific PPARG signaling pathway that is up-regulated in these cancers. Rather than using broad-spectrum chemotherapy, the invention isolates and addresses the specific molecular mechanism (PPARG activation) that drives these cancers, allowing for targeted intervention with inverse-agonists
2Productivity
If PPARG signaling is up-regulated in cancer cells, then cellular proliferation is increased, but targeted treatment options are limited
Solution Approach 1:
The patent applies inversion by using inverse-agonists that reverse the normal activation state of the PPARG receptor. Instead of agonists that activate PPARG or antagonists that merely block activation, inverse-agonists actively reverse the up-regulated signaling, inverting the molecular state from activated to inhibited and thereby reducing the increased cellular proliferation associated with PPARG-activated cancers
Solution Approach 2:
The patent converts the harmful up-regulation of PPARG signaling into a therapeutic opportunity by developing inverse-agonists that specifically target this up-regulated pathway. The very molecular characteristic that drives cancer progression (PPARG up-regulation) becomes the specific target for therapeutic intervention, allowing the harmful signaling to be converted into a benefit through targeted inhibition
Data Source
AI summary
The present disclosure provides compositions and methods for the treatment of PPARG activated cancer. For example, the present disclosure provides PPARG signaling modulators for the treatment of bladder cancer. In particular, therapeutic and/or prophylactic compositions and uses of PPARG inverse-agonists are described.