Patient-Specific cfDNA Mutation Tracking for Tumour Recurrence
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Solution Overview
Problem
Current methods for detecting tumor recurrence in non-small cell lung cancer are inadequate, particularly in the early stages, with existing cell-free DNA (cfDNA) profiling techniques lacking sensitivity and specificity, leading to delayed detection and limited treatment options.
Innovation Solution
A subject-specific method for detecting tumor recurrence by sequencing the genome or exome of a tumor to identify clonal and subclonal mutations, generating a bespoke biomarker profile unique to the patient, and analyzing cfDNA for the presence of these mutations to track disease progression and recurrence.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If generic gene panels are used for cfDNA profiling in early-stage lung cancer, then the method can be applied broadly, but the sensitivity and specificity of tumor recurrence detection is reduced
Solution Approach 1:
The patent segments the detection approach by dividing it into two distinct phases: (1) initial tumor sequencing to identify patient-specific clonal and subclonal mutations, and (2) subsequent cfDNA analysis using a customized panel targeting those specific mutations. This segmentation allows the method to be both broadly applicable and highly precise for each patient.
Solution Approach 2:
The patent applies local quality by creating a personalized detection panel for each patient that targets their specific tumor mutations. Instead of using a uniform generic panel for all patients, each patient receives a customized panel with high sensitivity for their particular cancer profile, thereby improving detection precision locally for each individual case.
2Measurement precision
If patient-specific customized panels are used for cfDNA analysis, then the sensitivity and specificity of detection is improved, but the complexity of the methodology increases
Solution Approach 1:
The patent applies preliminary action by performing comprehensive tumor sequencing and phylogenetic tree construction before the actual cfDNA detection phase. This upfront work identifies all relevant clonal and subclonal mutations, allowing the subsequent cfDNA analysis to focus only on those specific variants, thereby simplifying the ongoing monitoring process despite the initial complexity.
Solution Approach 2:
The patent uses copying by creating a digital reference profile (the phylogenetic tree with identified mutations) from the initial tumor sequencing that can be repeatedly used for comparing against subsequent cfDNA samples. This reference copy eliminates the need to resequence the entire genome each time, reducing the complexity of repeated measurements while maintaining high sensitivity.
3Loss of time
If clonal and subclonal mutations are tracked to identify metastatic subclones, then early intervention opportunities are enabled, but the requirement for comprehensive tumor sequencing increases
Solution Approach 1:
The patent extracts only the relevant information needed for recurrence detection by identifying and isolating specific clonal and subclonal mutations from the comprehensive tumor sequencing data. Rather than requiring complete genomic monitoring, the method extracts the key phylogenetic markers that indicate tumor recurrence, reducing the complexity of ongoing surveillance while maintaining early detection capability.
Solution Approach 2:
The patent performs comprehensive genome or exome sequencing as a preliminary one-time action at the time of initial tumor diagnosis to establish the patient's phylogenetic tree. This upfront comprehensive analysis enables subsequent non-invasive cfDNA tests to focus on tracking specific mutations, thereby achieving early intervention capability without requiring repeated comprehensive sequencing.
Data Source
AI summary
The invention relates to subject-specific methods for detecting recurrence of tumours based on an understanding of the clonal/subclonal mutation profile of the subject's tumour and detection of the mutations in their cell-free DNA (cfDNA), typically by multiplex PCR of tumour mutations such as single nucleotide variants (SNVs).