Illustration of circulating tumor cells with varying levels of visibility, representing the heterogeneity of CTCs and the potential for personalized medicine.

Decoding Cancer's Cloaking Device: New Insights into Circulating Tumor Cells

"Unlocking the Secrets of CTC Heterogeneity for Personalized Cancer Treatment"


Metastasis, the spread of cancer from its primary site, remains the leading cause of cancer-related deaths. This complex process involves the release of circulating tumor cells (CTCs) into the bloodstream, acting as seeds for new tumors in distant organs. Understanding CTCs is crucial for developing strategies to prevent and treat metastasis.

Liquid biopsies, which analyze CTCs in blood samples, have emerged as a promising tool for cancer diagnosis, monitoring, and treatment planning. However, current methods often rely on detecting specific markers, like EPCAM, on the surface of CTCs. This approach overlooks the fact that CTCs can be highly diverse, with some shedding or reducing these markers as they undergo epithelial-mesenchymal transition (EMT), a process that allows them to become more mobile and invasive.

A recent study published in Biomarker Research introduces a novel approach to identify and characterize CTCs, regardless of their EPCAM expression. By using patient-derived xenografts (PDXs) – models where patient tumor cells are grown in mice – and a highly sensitive human-specific qRT-PCR assay, researchers were able to quantify CTCs and analyze their gene expression profiles, offering new insights into CTC heterogeneity and potential therapeutic targets.

Beyond EPCAM: A New Strategy for CTC Detection

Illustration of circulating tumor cells with varying levels of visibility, representing the heterogeneity of CTCs and the potential for personalized medicine.

The limitations of current CTC detection methods, which primarily rely on the presence of epithelial markers like EPCAM, have prompted researchers to seek alternative approaches. The study in Biomarker Research tackles this challenge by employing patient-derived xenografts (PDXs). These models allow for the study of human CTCs in a murine genetic background, minimizing contamination from normal human cells.

The researchers developed a quantitative reverse transcription PCR (qRT-PCR) assay to detect human-specific transcripts in the blood of PDX models. This method circumvents the need for pre-selection or enrichment of CTCs based on surface markers, enabling a more comprehensive analysis of CTC populations.

The key benefits of this approach include:
  • Unbiased Detection: It identifies CTCs irrespective of EPCAM expression, capturing a wider spectrum of tumor cells.
  • High Sensitivity: The qRT-PCR assay allows for the detection of rare human transcripts in the murine background.
  • Heterogeneity Analysis: The method enables the characterization of gene expression profiles in CTCs, providing insights into their diverse nature.
Using this method, researchers analyzed CTCs in a cohort of breast cancer PDX models, quantifying the expression of EPCAM, KRT19 (another common CTC marker), and two reference genes (ACTB and OAZ1). The results revealed significant heterogeneity in EPCAM expression among CTCs, suggesting that relying solely on this marker may lead to an underestimation of CTC numbers and a biased view of their characteristics.

Implications for Personalized Cancer Therapy

The findings of this study have significant implications for personalized cancer therapy. By identifying and characterizing CTCs independently of EPCAM expression, clinicians can gain a more complete understanding of the metastatic potential of a patient's tumor. This, in turn, can lead to more informed treatment decisions and the development of targeted therapies that address the specific characteristics of a patient's CTCs.

The researchers propose that their approach could be used to identify novel CTC markers, which could then be used to develop new capture and detection methods. This would allow for the isolation and characterization of viable, heterogeneous CTCs, providing a valuable resource for drug development and personalized medicine.

While this study focuses on breast cancer PDX models, the approach can be extended to other cancer types. The ability to comprehensively analyze CTCs, regardless of their epithelial marker expression, holds great promise for improving cancer diagnosis, monitoring, and treatment, ultimately leading to better outcomes for patients.

About this Article -

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This article is based on research published under:

DOI-LINK: 10.1186/s40364-018-0145-8, Alternate LINK

Title: Heterogeneous Expression Of Epcam In Human Circulating Tumour Cells From Patient-Derived Xenografts

Subject: Biochemistry (medical)

Journal: Biomarker Research

Publisher: Springer Science and Business Media LLC

Authors: Chiara Agnoletto, Linda Minotti, Laura Brulle-Soumare, Lorenzo Pasquali, Marco Galasso, Fabio Corrà, Federica Baldassari, Jean-Gabriel Judde, Stefano Cairo, Stefano Volinia

Published: 2018-10-30

Everything You Need To Know

1

What is Metastasis and why are Circulating Tumor Cells (CTCs) important?

Metastasis is the spread of cancer cells from the original tumor site to other parts of the body, which is the leading cause of cancer-related deaths. Circulating Tumor Cells (CTCs) are cancer cells that detach from a primary tumor and enter the bloodstream. Understanding CTCs is crucial because they are the seeds for new tumors in distant organs. This study focuses on improving the detection and analysis of CTCs to better understand and potentially prevent or treat metastasis.

2

What are liquid biopsies, and why are they relevant to this research?

Liquid biopsies are blood tests that analyze Circulating Tumor Cells (CTCs) to help with cancer diagnosis, monitoring, and treatment planning. This study introduces a new approach to improve the accuracy of liquid biopsies. Current methods for detecting CTCs often use markers like EPCAM, but the study found that relying solely on these markers may not identify all CTCs because of the diversity of CTCs.

3

How does the study identify and analyze Circulating Tumor Cells (CTCs)?

The study uses patient-derived xenografts (PDXs) to study human Circulating Tumor Cells (CTCs) in mice. PDXs are models where patient tumor cells are grown in mice. Researchers also use a quantitative reverse transcription PCR (qRT-PCR) assay to detect specific human genes in the blood. This approach helps to identify and characterize CTCs irrespective of EPCAM expression, allowing for a more complete analysis of CTCs.

4

What is EPCAM, and why is its expression important in the context of CTCs?

EPCAM is a common marker used to identify Circulating Tumor Cells (CTCs). However, the study found that not all CTCs express EPCAM. Some CTCs shed or reduce this marker as they undergo epithelial-mesenchymal transition (EMT), a process making them more mobile and invasive. The study's new method can detect CTCs even if they don't have EPCAM, providing a more complete view of the CTC population.

5

How do the results of this study impact cancer treatment?

The study's findings have implications for personalized cancer therapy by improving our understanding of Circulating Tumor Cells (CTCs). By identifying and characterizing CTCs irrespective of EPCAM expression, clinicians can gain a more complete understanding of the metastatic potential of a patient's tumor. This enables more informed treatment decisions and the development of targeted therapies that address the specific characteristics of a patient's CTCs.

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