Radiosensitivity Prediction Using Stress-Induced Biomarker Detection

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Solution Overview

Problem

Current methods for predicting radiosensitivity in patients undergoing radiotherapy lack sensitivity and specificity, are technically cumbersome, and require invasive procedures, making them unsuitable for clinical routine use.

Innovation Solution

A method involving the induction of exogenous stress on biological samples to identify differentially expressed compounds such as mitochondrial isocitrate dehydrogenase 2 (IDH2), DNA-(apurinic or apyrimidinic site) lyase (APEX1), Heat shock cognate protein 71 kDa (HSC70), adenylate kinase (AK2), and annexin A1 (ANX1), which serve as predictive biomarkers for radiosensitivity, allowing for a rapid and reliable assessment of tissue radiosensitivity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If existing predictive tests for radiosensitivity are used, then some predictive information is obtained, but sensitivity and specificity are insufficient and technical complexity increases

Engineering Contradiction:
Improvepredictive accuracyVSAvoidtechnical complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent extracts and measures specific proteins (γ-H2AX, 53BP1, HSC70) that are directly involved in the DNA damage response and heat shock response pathways. By focusing on these key biomarkers rather than comprehensive genomic or proteomic profiling, the method achieves high predictive accuracy with simplified technical procedures suitable for clinical routine.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent uses proteins as intermediary biomarkers that mediate between radiation exposure and clinical outcomes. These proteins serve as measurable indicators that reflect the biological response to radiation, enabling indirect but accurate prediction of radiosensitivity without requiring direct observation of cellular function or complex genetic analysis.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If existing predictive tests are implemented, then radiosensitivity assessment is possible, but procedural complexity and time requirements increase

Engineering Contradiction:
Improvepredictive reliabilityVSAvoidassessment time
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The patent measures protein levels before radiotherapy treatment begins, establishing a baseline predictive assessment. This preliminary measurement of γ-H2AX, 53BP1, and HSC70 allows clinicians to determine radiosensitivity in advance, enabling treatment planning optimization without requiring repeated assessments during the treatment course.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent changes the measurement parameter from complex functional assays (such as cell survival curves or genomic sequencing) to simple protein concentration measurements. This parameter change enables rapid quantification using standard ELISA or Western blot techniques, reducing assessment time while maintaining reliable predictive accuracy.

Inventive Principle:
Principle #35Parameter changes

3Measurement precision

If existing predictive methods are used, then some radiotoxicity prediction is achieved, but procedural invasiveness and complexity increase

Engineering Contradiction:
Improveprediction accuracyVSAvoidprocedural simplicity
Core Design Contradiction:
Measurement precisionVSEase of operation

Solution Approach 1:

The patent uses conventional, widely available laboratory reagents and detection methods (ELISA kits, antibodies) that are inexpensive and routine in clinical laboratories. These disposable, off-the-shelf tools eliminate the need for specialized equipment or complex assay development, making the predictive test easy to implement in any standard medical laboratory.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

Solution Approach 2:

The patent employs proteins that are universally expressed in human cells and respond to radiation in a consistent manner across different patient populations. The same biomarkers (γ-H2AX, 53BP1, HSC70) can be measured using standardized protocols regardless of the patient's age, gender, or cancer type, simplifying the overall procedure and enabling broad clinical application.

Inventive Principle:
Principle #6Universality (Multi-functionality)

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 method enhances predictive value, enabling the identification of hypersensitive patients and potentially increasing radiation doses for non-hypersensitive patients, thereby improving therapeutic outcomes and reducing side effects, with the potential for increased cure rates and improved tumor control.

Implementation Method 1

The success of radiotherapy mainly depends on the total administered dose. Individuals vary widely in the susceptibility of the tissue to ionizing radiation damage.

Methodology Applied
Scientific EffectIonizing radiation: Radiation

Implementation Method 2

The radiation-induced lymphocyte apoptosis (RILA) assay measures the apoptosis in CD4 and CD8 T-lymphocytes after irradiation (0.5-8 Gy) via flow cytometry

Methodology Applied
Scientific EffectApoptosis:

Data Source

PatentEP2981331B1Method for determining radiosensitivity
Publication Date: 2018.11.28 CENTRE HOSPITALIER UNIVERSITAIRE DE MONTPELLIER
  • EP2981331B1 patent drawingFigure 1
  • EP2981331B1 patent drawingFigure 2
  • EP2981331B1 patent drawingFigure 3~4

AI summary

The present invention relates to a method for the in vitro determination of the radiosensitivity of a subject. More particularly, the invention relates to a method comprising a step of inducing an exogenous stress on a biological sample from a subject, followed by the comparison of the presence or level of at least one compound chosen in a group of defined compounds, in said biological sample and in a reference sample. The present invention also relates to the use of said at least one compound as predictive biomarker of the radio–sensitivity of a subject. The invention also relates to a kit for the detection of the presence or level of at least one of said compounds, usable in a method according to the invention.