GDF15 Propeptide Detection for Castration-Resistant Prostate Cancer

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Solution Overview

Problem

Current methods for detecting castration-resistant prostate cancer (CRPC) are inadequate, as they rely heavily on PSA measurements, which are not necessarily associated with the disease state and often result in late diagnosis due to the variability in the onset of castration resistance, leading to delayed detection of bone metastasis and disease progression.

Innovation Solution

The development of a method and reagent for detecting GDF15 propeptide and its degradation products in blood samples, utilizing specific antibodies and mass spectrometry to measure intact and fragmented forms of the propeptide, providing a novel marker for CRPC detection.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If PSA measurement is used for CRPC detection, then the detection method is simple and widely available, but the detection accuracy is low and diagnosis is delayed

Engineering Contradiction:

Improvedetection method simplicityVSAvoidCRPC detection accuracy

Core Design Contradiction:

Ease of operationVSMeasurement precision

Solution Approach 1:

The invention segments the GDF15 protein into two distinct detectable forms: the propeptide portion and the mature body portion. By developing separate detection methods for each segment, the patent achieves more accurate CRPC detection compared to using PSA alone, while maintaining operational simplicity through blood-based measurement

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The invention changes the detection parameter from PSA levels to GDF15 levels (specifically the propeptide and mature body portions). This parameter change enables accurate detection of CRPC onset, as GDF15 levels increase specifically when castration resistance develops, providing a more reliable diagnostic marker than PSA

Inventive Principle:

Principle #35Parameter changes

2Device complexity

If PSA is used as the sole marker, then the detection process is simple, but the onset of castration resistance cannot be detected early due to variability in disease progression

Engineering Contradiction:

Improvedetection system complexityVSAvoiddiagnosis timing delay

Core Design Contradiction:

Device complexityVSLoss of time

Solution Approach 1:

The invention enables preliminary detection of CRPC by measuring GDF15 propeptide levels before clinical symptoms of castration resistance appear. Since GDF15 propeptide increases specifically when androgen receptor signaling becomes independent of androgen levels, this marker provides early warning of impending castration resistance, allowing timely intervention before disease progression

Inventive Principle:

Principle #10Preliminary action

3Measurement precision

If GDF15 propeptide detection is implemented, then the detection accuracy for CRPC is significantly improved, but the detection method becomes more complex

Engineering Contradiction:

ImproveCRPC detection accuracyVSAvoiddetection method complexity

Core Design Contradiction:

Measurement precisionVSDevice complexity

Solution Approach 1:

The invention uses GDF15 propeptide as an intermediary marker that indirectly reflects the development of castration resistance. Rather than directly measuring androgen receptor activity or tumor burden, the propeptide serves as a biomarker that correlates with the molecular changes occurring during CRPC development, enabling accurate detection through a relatively simple blood test

Inventive Principle:

Principle #24Intermediary (Mediator)

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 enables simple and highly accurate detection of CRPC, offering a companion diagnostic tool for prostate cancer treatment and potentially improving therapeutic outcomes by enabling early identification of castration resistance.

Implementation Method 1

measurement is carried out using antigen-antibody reaction using an antibody that recognizes GDF15 propeptide

Methodology Applied

Scientific EffectAntigen-antibody reaction:

Implementation Method 2

measurement is carried out using mass spectrometry

Methodology Applied

Scientific EffectMass spectrometry:

Data Source

PatentUS11604194B2Method for detecting castration-resistant prostate cancer and detection reagent

Publication Date: 2023.03.14 TOSOH CORP

AI summary

The present invention aims to provide a method for simply and highly accurately detecting castration-resistant prostate cancer (CRPC), and a reagent that can be used for this method. By measuring the level of GDF15 propeptide present in a sample as a novel detection marker for CRPC, acquisition of castration resistance in a prostate cancer patient during or after endocrine therapy is detected. An antibody that specifically recognizes GDF15 propeptide is included in the CRPC detection reagent.