Diagnosing breast cancer through liquid biopsy

Breast cancer diagnosis usually includes invasive testing with tissue biopsies. The samples have to be extracted from the cancerous tissue or cells. To make the process easier on the patients, the project LIBIMEDOTS is currently developing a different approach with liquid biopsy technology.

In this MEDICA-tradefair.com interview, Dr. Neus Feliu Torres talks about the process of liquid biopsies and how using nanotechnologies would improve breast cancer diagnosis.

What is the goal of the LIBIMEDOTS project?

Dr. Neus Feliu Torres: LIBIMEDOTS project aims to develop efficient and gentle methods (non-invasive) for the diagnosis of breast cancer based on blood samples. In the project, we are using nanotechnology as an emerging technology and promising alternative method. For that, different magnetic and fluorescent nanoparticles are developed to specifically enrich and detect tumor circulating cells in the blood in a highly sensitive and affine manner. The benefits of using nanoparticles for biosensing include high sensitivity, specificity, detectability, quick analysis, low cost, easy bioconjugation, and the prospective for portability (point-of-care testing) and personalized medicine. Within this project, we collaborate with scientists from Catalan Rovira i Virgili University (Prof Ramon Alvarez-Puebla, expert in the development of optical biological sensors and data mining), Hamburg University (Prof Wolfgang Parak, expert in nanoparticle synthesis and biological applications), and the Medical Center Hamburg-Eppendorf (Prof Klaus Pantel, leading expert on liquid biopsies).

What would be the advantages of a liquid biopsy compared to conventional biopsies?

Feliu Torres: Conventionally, a cancer diagnosis is secured by tissue biopsy and immunohistochemical analysis. This involves taking a sample of the cancerous tissue or cells. Tissue biopsies are invasive, time-consuming, costly, painful, potentially risky, or sometimes even not feasible for patients. Furthermore, they cannot track the disease status and progression in real time. In contrast, liquid biopsies are not afflicted with these drawbacks, they do not examine tumor tissue directly. Instead, liquid biopsy aims to detect tumor markers in body fluids noninvasive. They are quick, less expensive, and exhibit the possibility to monitor cancer over time (due to repeat sampling), allowing personalized medicine.

What is the process for a liquid biopsy?

Feliu Torres: Liquid biopsy is presented as an alternative to surgical biopsies, enabling medical doctors to discover a range of information about cancer-related material – for example, tumor DNA – from blood or other fluidic samples. Briefly, as an example, the doctor will take a blood sample and they will send it to a laboratory to analyze signs of diseases using several new analytical methods. With our method, we aim to develop specific affine magnetic and fluorescent nanoparticles to detect little cancer cells in a very specific manner.  Briefly, the nanoparticles will be added to the extracted patient blood samples, and after specific binding procedures, cancer cells could be detected with fluorescence. The advantage of using fluorescent nanoparticles is, that they do not present photobleaching and are photostable in contrast to many common fluorescent dyes.

Why is the research focused on breast cancer?

Feliu Torres: Breast cancer is one of the most frequently diagnosed tumors in women, with a very high worldwide occurrence annually. Thus, we decided to develop our nanotechnology liquid biopsy diagnosis method for the detection of breast cancer. However, our nanotechnology base methodology could be adapted to other types of diseases and cancers.

What do you hope to achieve with liquid biopsies in the future?

Feliu Torres: Nowadays, liquid biopsy cannot replace a tumor biopsy and it is used as supportive information to the traditional analytical methods. However, in the future, we aim to establish liquid biopsy as a tool for cancer screening. Liquid biopsies could help to monitor a patient’s response to therapy in a more personalized manner by analyzing samples before and during patient treatment.

I believe that significant advances in nanotechnology, through the use of micro- and nanostructured systems, will contribute to the development of liquid biopsy methods with higher sensitivity and specificity. The use of nanoparticles is especially valuable in this field for signal enhancement, as they do not need enzymatic reactions or several enhancement steps. The detection of cancer biomarkers, such as circulating tumor (ctDNA), circulating tumor cells (CTCs), or exosomes is a challenge, due to their low abundance in blood circulation. For these reasons, enhancers are required for the analysis. Nanoparticles could enhance the detection of the low abundance of cancer biomarkers in blood circulation, which is currently a significant challenge for doctors and analysts.  They will bring new insights into clinical practice, allowing the development of early detection methods for the real-time monitoring of diseases.

In addition, to obtain relevant information about the tumor and metastasis, this research field is moving towards multiomics analysis. This means a simultaneous detection and analysis of different biomarkers. Nanoparticles exhibit this capability as well; thus, they have great potential in liquid biopsy methods contributing to the multiplex analysis.

What stage is your project at this point? What are the next steps?

Feliu Torres: We are currently developing a library of different magnetic and fluorescence nanoparticles to find the best candidates to be applied for the detection of cancer cells. We are trying to optimize the best magnetic nanoparticles that will allow the highest affective pre -enrich of blood cells. At the same time, we are optimizing the specific target capabilities of the fluorescent nanoparticles, aimed to be used to decorate and detect the cancer cells in a very specific manner using a fluorescence approach. With some selective nanoparticles, we are currently performing in vitro tests.