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Liquid biopsies : a promising alternative for cancer detection

João miguel alves

Nationality Potuguese

Year of selection 2017

Institution Universidade de Vigo

Country Spain

Risk Health

Post-Doctoral Fellowship

2 years

130000 €

Cancers display a startling degree of diversity. This heterogeneity is not only observed between patients but within individuals as well. A single tumour can be composed of a genetically diverse population of cancer cells. Yet, traditional tumour biopsies, because they only allow the sampling of a small piece of tissue, fail to reflect this diversity. Dr. João Miguel Alvès, a post-doctoral researcher at the University of Vigo, in Spain, is evaluating the potential of blood-based “liquid biopsies” as a more refined method for cancer diagnosis. More specifically, he aims to investigate how the information derived from tumour cells circulating in the blood stream (CTCs) can be used as an indicator of tumour aggressiveness in colorectal cancer. In exploring the clinical significance of CTCs, his project ultimately aims at paving the way for more precise and more efficient patient-specific therapeutic strategies.

«The research community has only recently discovered that cancer is very heterogenous in terms of genetic composition, reports Dr. Alves. The whole field is all very new, just a few years old». «This realization reduces the value of traditional single tissue biopsies, he goes on to explain. Because by capturing just a fraction of the tumour’s characteristics, they lead to inadequate treatment strategies». Cancer is a dynamic disease. With time, cancers generally become more heterogeneous. As a result of mutations, cells within the tumour can harbour distinct molecular signatures with differential levels of sensitivity to treatment. «A consequence is that heterogenous tumours account for more mortality», explains the researcher. Capturing this diversity is thus essential, but how? What diagnosis method can be used? «We know that cancer-derived materials travel in the blood of patients. Among them are intact tumour cells, called CTCs, shed from primary or metastatic tumour deposits.» In other words, a simple non-invasive blood test could perhaps allow for a much more representative sampling of cancer diversity than a traditional invasive biopsy. Building on the availability of new technologies, the present project aims to put this hypothesis to the test by providing answers to the following questions: can CTCs be used to show the actual diversity of cancer cells within a patient? And if they can, can we correlate this information with the overall survival rates, to use as an indicator of the patient’s level of risk?»

Understanding tumour heterogeneity: the next big quest in cancer science

Because this area of research is so recent, studies about circulating tumour cells have so far mostly focused on enumeration alone. The number of CTCs present in the blood – only between 5 and 50 units per teaspoon of blood –, is used to classify the patient’s level risk. «The problem with that method , aside from the fact that you need a very powerful instrument in order to get an accurate number, is that it fails to take into account the variability among these cells, Dr. Alvès points out. Our study aims to go further and not just count the CTCs, but differentiate them by sequencing their genome». « Advances in the isolation of CTCs, together with technological improvements that enable single-cell genome resolution, suggest that it may be possible to quantify the contribution of CTC diversity towards disease progression », he continues. To carry out his project, Dr. Alvès is working hand in hand with three hospitals where patients with colorectal cancers are being treated. His methodology will consist of collecting blood samples from a total of 100 patients, then using state-of-the-art laboratory instruments to isolate the circulating tumour cells and sequence their genome, and finally exploiting the data collected to determine diversity statistics and compare them with the patient’s survival rates. This way, he expects to answer «crucial questions regarding the dynamics of CTCs and the potential prognostic role of CTC diversity».

The ability to study cancers with blood sampling is one of the most promising and rapidly advancing fields in cancer diagnostics. The accessibility of Circulating tumour cells, as well as the fact that they can originate from different places in the body, makes them incredibly precious sources of information about cancers. Information that researchers think could be key to cancer diagnosis or treatment. By focusing his research on whether the genetic landscape of CTCs can serve as an ideal proxy of the overall tumour diversity, Dr. Alvès’ approach is likely to make a significant contribution to this emerging field of research.