Prostatic Liquid Biopsy Using Cell Shedding Induction
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current prostate cancer detection methods, such as needle biopsies and biomarker tests, are invasive, painful, and prone to false negatives and false positives, leading to unnecessary treatments and complications, while non-invasive methods lack the sensitivity and specificity to accurately detect prostate cancer.
Innovation Solution
Administering 5-alpha reductase inhibitors like Finasteride to facilitate the dislodgment and migration of prostatic epithelial cells into the urethra for collection, combined with mechanical manipulation, to enhance the sampling of prostate cells through minimally invasive means.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If prostate biopsy is performed using traditional methods (transrectal ultrasound-guided needle biopsy), then tissue samples can be obtained for diagnosis, but there is a risk of infecting the bloodstream with bacteria from the rectum and contamination of the sample with rectal flora
Solution Approach 1:
The patent introduces an intermediary approach by using molecular markers (PCA3, TMPRSS2:ERG fusion gene, PCA3/PSA ratio) as mediators between the biopsy procedure and diagnostic accuracy. These molecular markers serve as intermediaries that can identify prostate cancer cells specifically without requiring direct tissue sampling that risks contamination. The molecular markers act as a bridge that provides diagnostic information while avoiding the harmful contamination pathway.
Solution Approach 2:
The patent extracts the diagnostic information needed for cancer detection by isolating and measuring specific molecular markers (PCA3, TMPRSS2:ERG fusion gene) from the complex biological environment. Instead of relying on tissue morphology that can be contaminated by rectal flora, the method extracts and measures specific RNA or DNA sequences that are uniquely expressed in prostate cancer cells, thereby separating the diagnostic signal from the contaminating background.
2Object-affected harmful factors
If transperineal biopsy is used to avoid rectal contamination, then sample contamination is reduced, but the procedure is more complex and requires patient positioning and potentially general anesthesia
Solution Approach 1:
The patent replaces the mechanical tissue sampling system with a molecular detection system. Instead of physically inserting needles through the perineum or rectum to obtain tissue samples, the method uses molecular markers (PCA3, TMPRSS2:ERG fusion gene) that can be detected through less invasive means. This substitution eliminates the need for complex mechanical biopsy procedures while maintaining diagnostic capability through molecular analysis.
Solution Approach 2:
The patent changes the diagnostic parameter from tissue morphology (requiring physical biopsy) to molecular expression levels (RNA/DNA sequences). By measuring the expression levels of PCA3 gene or TMPRSS2:ERG fusion gene, the diagnostic approach shifts from a mechanical procedure to a molecular measurement, fundamentally changing the parameter being assessed and enabling less invasive sampling methods.
3Measurement precision
If multiple tissue samples are taken during biopsy to improve diagnostic accuracy, then detection sensitivity increases, but patient discomfort and procedure time increase
Solution Approach 1:
The patent makes the molecular marker detection system universal by designing it to work with minimal or single tissue samples. The PCA3 and TMPRSS2:ERG fusion gene markers are so specific and sensitive that they can provide accurate diagnostic information from a single sample or even from liquid biopsy materials, eliminating the need for multiple sequential biopsies. This multi-functional molecular assay can simultaneously detect presence, quantify burden, and guide treatment decisions.
Solution Approach 2:
The patent performs preliminary molecular analysis on initial biopsy samples or even on liquid biopsy samples obtained before traditional tissue biopsy. By measuring PCA3 expression or TMPRSS2:ERG fusion gene presence in advance, the system can determine whether further invasive biopsies are necessary, potentially eliminating the need for multiple tissue sampling procedures and reducing overall procedure time.
Data Source
Figure 1~2
Figure 3~4
Figure 5
AI summary
Disclosed are methods to induce dislodgement of target prostatic cells from the prostate organ, collecting said cells, and subsequently examining the cell population. Such methods comprise the administration of an agent that facilitates the dislodgement of the target cells from within the prostate, which then migrate into the urethra. Exemplary agents include 5 alpha-reductase inhibitors. The cells induced to pass into the urethra are then collected non-invasively, such as through urine or semen samples. Such collection is further strategically calculated relative the administration of the agent so as to maximize the sample collection of the target cells of interest. The exfoliated prostatic epithelial cells are subsequently utilized for purposes such as detecting prostate cancer, predicting/measuring prostate tumor susceptibility to drug regimes, active surveillance of patients whose prostate biopsy results are negative, but continue to exhibit symptoms consistent with prostate cancer, and identifying false positive results associated with biomarker assays.