AnnexinA2 and Circulating Tumor Stem Cell Detection for Cancer Diagnosis
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current methods for diagnosing cancer, particularly in early stages and distinguishing between benign and cancerous tumors, are inefficient due to the rarity of circulating tumor cells and the lack of effective markers for pre-cancerous conditions, leading to poor detection of metastatic potential and recurrence.
Innovation Solution
Measuring the levels of AnnexinA2 in serum or blood in combination with the presence of circulating tumor stem cells positive for CS-ANXA2 and stem cell markers DCAMKL and Lgr5 to diagnose pre-cancerous growths and differentiate between early and late-stage cancers.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If circulating tumor cells are measured using current methods (immunocytochemistry, RT-PCR, EpCAM-based selection), then cancer detection is possible, but detection efficiency is poor due to the rarity of cancer cells among blood cells
Solution Approach 1:
The patent changes the detection parameters by using AnnexinA2 as a new biomarker instead of traditional EpCAM or cytokeratin markers. This parameter change enables more efficient detection of circulating tumor cells by targeting a protein that is specifically upregulated on the surface of tumor cells, particularly at the leading edges of invasive tumors, thereby improving both detection accuracy and efficiency
Solution Approach 2:
The patent uses soluble AnnexinA2 in serum as a surrogate marker that copies the information about tumor presence and progression. By measuring the concentration of soluble AnnexinA2 released into the bloodstream, the method provides an efficient indirect detection approach that avoids the need to physically isolate and analyze rare circulating tumor cells
2Adaptability or versatility
If traditional cancer markers are used, then cancerous tumors can be detected, but pre-cancerous benign tumors cannot be distinguished
Solution Approach 1:
The patent applies local quality by differentiating between intracellular AnnexinA2 (present in all cells) and cell-surface associated AnnexinA2 (CS-ANXA2, specifically upregulated on tumor cells). This localized expression pattern on the cell surface and its release into serum provides a specific signature that distinguishes pre-cancerous and cancerous conditions from benign tumors, enabling the diagnostic method to adapt to different disease stages with precision
3Productivity
If invasive cancer cells are detected using anti-EpCAM antibodies, then circulating tumor cells can be captured, but invasive cells with highest metastatic potential may be under-evaluated due to loss of EpCAM expression
Solution Approach 1:
Instead of using EpCAM to capture circulating tumor cells, the patent inverts the approach by using AnnexinA2, which is upregulated on the cell surface of invasive tumor cells. This inversion ensures that cells with the highest metastatic potential (which have lost EpCAM but gained AnnexinA2) are specifically targeted and detected, thereby improving both capture efficiency and metastatic potential assessment
Data Source
AI summary
Provided herein is a method for diagnosing/prognosing a metastatic cancer in a subject by measuring and detecting one or more of CS-ANXA2, DCAMKL, Lgr5 or CS-ANAX2 and DCAMKL or CS-ANXA2 and Lgr5 positive circulating tumor stem cells in the subject's blood or plasma. Also provided is a method for distinguishing the presence of early stage primary cancer from advanced stage metastatic cancer in the subject by measuring and detecting AnnexinA2, CS-ANXA2 and DCAMKL-1 or Lgr5 in the blood or plasma. In addition, there is provided a method for distinguishing the presence of benign, pre-cancerous tumorous growths or cancerous tumors in the subject by measuring and detecting AnnexinA2 and circulating tumor stem cells positive for CS-ANXA2 and DCAMKL or CS-ANXA2 and Lgr5 in the blood or plasma.