Circulating Tumor Cell Detection via Mesenchymal Phenotype Analysis
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Solution Overview
Problem
Current methods for monitoring prostate cancer progression and therapy response lack reliable and accurate biomarkers, particularly for castration-resistant prostate cancer, where existing biomarkers like PSA are insufficient, and invasive tissue biopsies are costly and impractical for frequent sampling.
Innovation Solution
A novel method involving multiple rounds of fluorescence in situ hybridization (FISH) after immunofluorescence staining to identify epithelial and mesenchymal cell features in circulating tumor cells (CTCs) and the measurement of circulating megakaryocytes in blood samples to determine prognosis and monitor therapy response.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If tissue biopsies are used for frequent tumor sampling, then molecular and cellular features of cancer can be detected, but the invasive nature and cost make it impractical
Solution Approach 1:
The invention extracts and analyzes circulating tumor cells (CTCs) and megakaryocytes from blood samples, eliminating the need for invasive tissue biopsies. This allows frequent sampling to detect molecular and cellular features of cancer progression while avoiding the harms of repeated surgical procedures
Solution Approach 2:
The invention uses blood as an intermediary medium to access tumor information. By analyzing CTCs and megakaryocytes circulating in the blood, the system indirectly detects cancer molecular and cellular features without directly sampling the tumor tissue, thus resolving the contradiction between detection precision and ease of operation
2Quantity of substance
If current CTC technologies like CellSearch are used, then epithelial CTCs can be captured, but fewer than two CTCs are detected in many metastatic prostate cancer patients
Solution Approach 1:
The invention changes the detection parameters by targeting mesenchymal markers (CD45-, CK-, Vimentin+) instead of epithelial markers. This parameter change allows detection of mesenchymal CTCs that constitute the majority of circulating tumor cells in metastatic prostate cancer, thereby increasing both the quantity detected and the reliability of detection
Solution Approach 2:
The invention develops a universal detection method that identifies both epithelial and mesenchymal CTCs through immunofluorescence staining and FISH analysis. This multi-functional approach ensures reliable detection across different metastatic prostate cancer patients regardless of whether their CTCs exhibit epithelial or mesenchymal characteristics
3Ease of operation
If PSA is used as biomarker for disease monitoring, then it is widely available, but it is unsatisfactory when disease progresses to castration-resistant prostate cancer
Solution Approach 1:
The invention extracts and analyzes CTCs and megakaryocytes from blood samples as alternative biomarkers. These extracted cellular elements provide precise monitoring information for CRPC progression, replacing the insufficient PSA biomarker while maintaining ease of blood-based testing
Solution Approach 2:
The invention uses CTCs as a copy or surrogate representation of the primary tumor. By analyzing the molecular and cellular features of these circulating tumor cells, the system obtains accurate CRPC monitoring data without relying on the failing PSA biomarker, thus resolving the contradiction between availability and measurement precision
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 confirmation of malignancy in CTCs with a mesenchymal phenotype and identifies an increase in megakaryocytes associated with prostate cancer prognosis, providing a non-invasive and precise method for monitoring disease status and therapy response.
Implementation Method 1
multiple rounds of fluorescence in situ hybridization (FISH) on the same slides after immunofluorescence staining
Implementation Method 2
immunofluorescence staining to identify epithelial and mesenchymal cell features
Data Source
AI summary
The present invention provides a method for determining the prognosis of cancer in a subject. The method comprises measuring the amount of megakaryocytes in a sample from the subject. Usually, the sample is a blood sample. The method may also comprise measuring the number of circulating tumour cells (CTCs) in the sample, and in some embodiments a comparison of the number of megakaryocytes and CTCs in the sample. The present invention also provides methods of treatment for cancer in a patient for whom a poor prognosis is predicted using a method of prognosis of the invention.