Gene Panel Predicting Androgen Deprivation Therapy Response

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Solution Overview

Problem

Current treatments for prostate cancer, particularly androgen-deprivation therapy (ADT), face challenges in predicting response and managing resistance, due to the heterogeneity of prostate cancer and scarcity of genomic mutations, leading to therapeutic challenges and limited options for castration-resistant disease.

Innovation Solution

A method integrating DNA methylation and mRNA expression data to identify a panel of five differentially methylated sites (CSPG5, FKBP6, FOSB, STMN1, and TTC27) that predict primary resistance to ADT, allowing for personalized treatment decisions by measuring expression and methylation levels in prostate cancer samples.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If androgen-deprivation therapy (ADT) is used to treat prostate cancer, then initial response is achieved, but resistance develops after 2-3 years leading to castration-resistant disease

Engineering Contradiction:

Improvetherapeutic responseVSAvoidremission duration

Core Design Contradiction:

ReliabilityVSDuration of action of stationary object

Solution Approach 1:

The patent applies preliminary action by performing genomic profiling and gene expression analysis before initiating ADT to predict which patients will develop resistance. This allows clinicians to pre-identify patients at high risk of resistance (those with elevated expression of genes like FKBP6, FOSB, STMN1, TTC27, and CSPG5) and consider alternative treatment strategies beforehand, rather than waiting for resistance to develop after 2-3 years of remission.

Inventive Principle:

Principle #10Preliminary action

2Adaptability or versatility

If ADT is administered to all prostate cancer patients, then treatment coverage is maximized, but therapeutic effectiveness decreases due to heterogeneity and resistance

Engineering Contradiction:

Improvetreatment coverageVSAvoidtherapeutic effectiveness

Core Design Contradiction:

Adaptability or versatilityVSReliability

Solution Approach 1:

The patent applies local quality by moving from a uniform treatment approach to personalized treatment based on individual patient genomic profiles. Specifically, it identifies distinct molecular subtypes of prostate cancer through gene expression analysis (e.g., high FKBP6/FOSB/STMN1/TTC27/CSPG5 expression versus low expression), and recommends different therapeutic strategies for each subtype. This allows treatment to be tailored to the specific molecular characteristics of each patient's tumor, improving effectiveness while maintaining broad adaptability.

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The patent applies parameter changes by using genomic parameters (gene expression levels of specific genes) to stratify patients into different risk categories. By measuring and comparing expression levels of genes like FKBP6, FOSB, STMN1, TTC27, and CSPG5 against established thresholds, the system transforms continuous genomic data into discrete clinical decision parameters that guide treatment selection, thereby optimizing both coverage and effectiveness.

Inventive Principle:

Principle #35Parameter changes

3Adaptability or versatility

If genomic mutations are used to define prostate cancer subtypes, then molecular classification is attempted, but scarcity of mutations makes subtyping difficult

Engineering Contradiction:

Improvemolecular subtypingVSAvoidsubtyping complexity

Core Design Contradiction:

Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent applies mechanics substitution by replacing the traditional approach of identifying cancer subtypes through genomic mutations (which are scarce in prostate cancer) with an alternative mechanism based on gene expression profiling. Instead of searching for rare mutational events, the system measures mRNA expression levels of specific genes (FKBP6, FOSB, STMN1, TTC27, CSPG5) using techniques like RT-PCR or RNA sequencing, which provides a more abundant and informative molecular signature for subtyping and treatment prediction.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

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 accurately predicts ADT response across various patient cohorts, independent of Gleason score or therapy subtype, enabling prioritization of patients for effective treatment strategies and reducing the risk of resistance.

Implementation Method 1

DNA methylation (FIG. 1) is the addition of methyl group to the fifth position of cytosine (converting it to 5-methylcytosine). In mammals, methylation of cytosine often occurs in regions where cytosine is followed by guanine (connected through phosphate molecule), named a CpG site

Methodology Applied

Scientific EffectDNA methylation:

Implementation Method 2

Using a method that integrated DNA methylation and mRNA expression data, a panel of five differentially methylated sites were identified which explain expression changes in their site-harboring genes

Methodology Applied

Scientific EffectmRNA expression:

Data Source

PatentUS11299786B2Gene panel to predict response to androgen deprivation in prostate cancer

Publication Date: 2022.04.12 RUTGERS THE STATE UNIV

AI summary

Methods for predicting the response of prostate cancer to androgen deprivation therapy (ADT) using a gene signature of five genes (CSPG5, FKBP6, FOSB, STMN1, and TTC27) is provided. Also provided are sets containing specific binding molecules for each of CSPG5, FKBP6, FOSB, STMN1, and TTC27 and kits containing such sets.