MRD Detection via mRNA Expression Ratios
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Solution Overview
Problem
Current methods for detecting minimum residual disease (MRD) in cancer patients are limited by the lack of specific and sensitive markers, making it challenging to accurately identify and monitor MRD, particularly in conditions like neuroblastoma, where relapse often occurs due to undetectable residual tumor cells.
Innovation Solution
A method involving the measurement of mRNA expression levels of specific genes in tumor samples and comparison with normal or cured subjects' samples, using ratios to identify markers of MRD, with genes like CCND1, TH, and GD2 synthase, and employing techniques like qRT-PCR and Affymetrix biochips for accurate detection.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional radiographic or histopathological tools are used to detect cancer, then the detection method is simple and widely available, but the sensitivity is insufficient to detect minimum residual disease below visible thresholds
Solution Approach 1:
The patent replaces conventional radiographic and histopathological mechanical/optical detection systems with molecular-based PCR detection systems. This substitution enables detection of minimum residual disease at the molecular level, achieving sensitivity far below the threshold of visible or conventional imaging methods.
Solution Approach 2:
The patent introduces molecular markers (DNA, RNA, proteins) as intermediaries to detect the presence of residual tumor cells. These markers serve as mediators that amplify the detectable signal from individual or small numbers of residual cancer cells, making them detectable by PCR-based methods.
2Measurement precision
If molecular-based methods like PCR are used to detect tumor cells, then the sensitivity and specificity are greatly improved, but the detection is restricted to known tissue-specific antigens and tumor-associated mutations
Solution Approach 1:
The patent develops a universal molecular detection platform based on PCR technology that can detect multiple different tumor types and markers through a single system. By using universal primers and probes that can target various tissue-specific antigens and mutations, the method achieves both high specificity for known markers and versatility across different cancer types.
Solution Approach 2:
The patent employs dynamic marker selection where the detection targets (DNA, RNA, proteins) are chosen based on the specific tumor type and clinical context. This dynamic approach allows the same molecular platform to adapt to different cancer types by selecting appropriate markers, thereby achieving both specificity and versatility.
3Reliability
If treatment is delayed until tumors are measurable and symptomatic, then the treatment eligibility criteria are met, but the tumor has higher likelihood of mutations and resistance according to the Goldie-Coldman hypothesis
Solution Approach 1:
The patent enables preliminary detection of minimum residual disease using molecular markers before tumors become clinically apparent. This preliminary action allows clinicians to initiate treatment earlier based on molecular evidence of residual disease, rather than waiting for tumors to grow to measurable sizes, thereby preventing the development of resistance and improving treatment efficacy.
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 allows for the sensitive and specific identification of MRD markers, enabling early detection of residual tumor cells in blood and bone marrow, which is crucial for determining treatment efficacy and timing, and predicting progression-free survival and overall survival in cancer patients.
Implementation Method 1
quantitative reverse transcription-polymerase chain reaction (qRT-PCR) to measure tumor transcripts
Implementation Method 2
quantitative reverse transcription-polymerase chain reaction (qRT-PCR) to measure tumor transcripts
Implementation Method 3
measuring the mRNA expression level of a gene in a tumor; measuring the mRNA expression level of the gene in the bone marrow or peripheral blood
Data Source
AI summary
The present invention features methods and compositions for identifying markers of minimum residual disease (MRD), as well as markers of metastatic cells. The present invention further provides methods for detecting MRD and metastatic cell in a subject.