“When we analyzed the data, I had this feeling: as if so far, for each patient, we had had a very in-depth book of 500 pages with a lot of information, but with the last 10 – the ones with the conclusions – glued and illegible. . But suddenly we were managing to decipher them. ” We are in a laboratory of the Irccs Istituto Regina Elena – Ifo in Rome and to speak is Patrizio Giacomini, among the researchers of the team that carried out a study, LiqBreasTrack, which aims to understand how breast cancer evolves over time and how to combat drug resistance. How? Through simple blood tests, as the scientist tells Health Seno.
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One, none, one hundred thousand: the tumor is a changing entity
Here it is perhaps necessary to take a step back, to explain the context. To analyze the characteristics of a tumor, a tissue biopsy is used: that is, a small sample is taken and analyzed. In recent years, many advances have been made and technology makes it possible to sequence large parts of the tumor genome – that is, the DNA – in a short time, to discover its weak points. But tumors are not “static”: they are dynamic entities, which evolve over time to escape the effect of drugs, and sometimes change so much that they become insensitive to treatment. This phenomenon has been well studied in animal models, but it is difficult to document in clinical practice due to the small number of tumor cells from which this resistance originates. Not to mention that it is not practicable to repeatedly perform tissue biopsies in patients.
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What the liquid biopsy shows
How, then, to access this “black box”? One way is through liquid biopsy. Cancer cells and DNA, in fact, are also found in the blood of patients, and carry more information: “In the circulating tumor DNA we see different genetic alterations than those present in tissue biopsies – continues Giacomini – and some may be the target of targeted therapies: weak points that we would not have been able to see otherwise, and that can expand the range of therapies for those who thought they no longer had it “.
The preliminary study on 20 patients
The researchers observed it in 20 patients with HER2-positive advanced breast cancer treated with one of the standard therapies, the drug T-DM1 (trastuzumab emtansine). Their tumors changed rapidly, some even within weeks, and these changes were clearly visible in the blood as early as several months before the actual clinical progression of the disease: “At least 50% of the resistance we found in the blood was not identifiable in the tissue. of the tumor, neither in the primary lesion nor in the subsequent metastases. We were the first to be surprised “, says Giacomini.
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Play in advance against the tumor
There is a very practical clinical side to this whole story: almost all of the blood resistances observed corresponded to already existing targeting drugs. In other words, through the liquid biopsy it is possible to observe in a timely manner whether the tumor is developing resistance to the drug (and of what type) and, in theory, to correct the therapy in real time based on the mutations found. The conditional, however, is a must because the study – conducted by Giacomini together with Matteo Allegretti, research fellow of the Airc Foundation, and to the oncologist Alessandra Fabi, Published on Molecular Cell – is still preliminary. That is why a second, larger study was launched, involving 45 patients: if the results are confirmed, there will be further studies with the aim of treating patients based on the results of the liquid biopsy.
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“Liquid biopsy can take precision oncology to the next level,” says Giacomini. “And our way of doing research is changing: it leads to continuous and very close relationships between those who analyze the samples in the laboratory, the clinician who reads the analyzes and the patient. This research has been a unique experience for us also humanly: we were all together – women, doctors and researchers – united by a continuous exchange of information and experiences. Often – she concludes – we forget that the history of scientific research is a history of people “.
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