Liquid biopsy allows progress in the specific treatment of each individual
A blood test is undoubtedly one of the most common clinical tests in our hospitals, both to determine the physiological status of a patient and to make a good diagnosis of a disease. In all probability, the readers of this article have gone through this process more than once with no consequences, in the worst case, than a small bruise. However, it was not until the 1900th century, with the determination of blood groups (ABO) that blood tests became part of clinical practice. This incorporation into the clinical routine was not easy or quick, because even though Karl Landsteiner determined the ABO blood system in 1914, it would be several years before medical science appreciated its importance in performing blood transfusions. In fact, until blood type determination was used, the development of severe reactions, sometimes fatal, and most due to blood group incompatibilities was common. It was necessary to mediate the First World War (1918-XNUMX), with its millions of wounded, and the entry of the United States into the conflict, to standardize blood transfusion protocols. And it is that during the First World War transfusions became a daily routine that led to the development of these protocols. When these doctors returned home, blood transfusion gained a new place in civilian medical practice.
Precision medicine began then, with blood transfusion tests. Precision medicine is the great goal of contemporary medicine and within precision medicine one area stands out above all: liquid biopsy. But what is precision medicine and liquid biopsy really all about? Let's start by describing these concepts to the reader. Until relatively recently, the treatment and follow-up of patients prevailed, what we know as one size fits all, this could be translated into our language as "coffee for everyone", a very Spanish concept for which in this case we are not directly responsible and which means that different patients diagnosed with the same disease, or similar symptoms, receive the same clinical follow-up and the same treatment.
However, human biology is complex and diverse and each of us has our own barcode (our blood group for example). That is, each of us responds differently to stimuli, conflicts or, in the case at hand, to illness. One might ask, then, why do we treat two different patients the same, let's say Ernesto and Manuel, who, yes, are diagnosed with the same disease? The answer is simple: because we don't treat Ernesto or Manuel, but rather we treat the illness that Ernesto and Manuel have been diagnosed with. It should be noted, however, that this approach was successful at the time, providing excellent results and great advances in the treatment and management of patients. What would have happened to those patients affected by leukemia if Dr. Farber had not started study the biological complexity that this disease entails in order to treat them with the first chemotherapy drugs? However, this approach is obsolete due to its simplicity. Medicine accompanied by technological advances currently allows us to better understand the nature of the disease in each individual patient; that is, in the words of Dr. Gregorio Marañon, "let's treat the patient and not the disease."
Precision medicine tries to identify the most appropriate treatment scheme for each patient and, with individualized follow-up, determine early the response that they may develop to that treatment. To this definition, we should add, from my perspective, “and using non-aggressive methods”. Let us remember that one of the limitations that were imposed on the use of blood transfusions on a routine basis, and that deflated the spirits of some scientists, was precisely the use of aggressive and uncomfortable techniques for the patient, making them impossible as a routine technique (the transfusion involved cutting the skin and exposing the blood vessels, that is, surgery, which also involved immobilizing the patient for 2 to 3 hours). The follow-up of the patient in real time, and therefore the use of non-aggressive techniques, is especially important for cancer patients and it is so because cancer is not a static disease but rather a dynamic one, changing throughout space (metastasis ) and therefore time, and it does so based not only on the disease itself, but also on how the patient (host) responds to that disease.
LIQUID BIOPSY ALLOWS ADVANCE IN THE SPECIFIC TREATMENT OF EACH INDIVIDUAL
The reader may reflect, almost correctly, that this has been done in our hospitals for quite some time. Indeed, current methods, such as X-rays and various CT scans, have allowed us to determine how the patient is progressing. However, these techniques require time and a minimum tumor volume to be able to establish whether or not the patient is responding to treatment. If there is an important variable in successful cancer treatment, it is early intervention. One of the fundamental characteristics of cancer is its ability to invade other organs, which we know as metastasis. Actually, what can end the life of a patient is not the tumor itself, but the potential ability of tumor cells to leave their original niche to explore new territories, invading other organs, which ends up being incompatible with life. Therefore, early detection of this process is essential for patient survival.
We need additional methodologies that can cover that period of time during which current techniques are not sensitive enough. We are faced with an obstacle that is difficult to overcome, but if a scientist likes something, it is the great challenges. To the surprise of some, there are scientific dogmas that cannot change and if we are sure of one thing, it is that the colonization of other organs by tumor cells is not carried out by teleportation (quite a relief and do not look it up in our dictionary ... no appears. Our academics have not seen the series Star Trek) but instead use the transportation systems available to them. And ... what is the internal transport system that most living beings use? The circulatory system.
The circulatory system is made up of an essential fluid for our survival, blood. Our blood is responsible for transporting the cells necessary to carry out vital functions (breathing, forming substances, defending itself against aggressions), transporting the nutritional principles from the digestive system to the cells, collecting waste substances, regulating the transport of oxygen and the elimination of carbon dioxide, control of body temperature ... But it is also used by viruses and bacteria to spread and cause infections, just as tumor cells use it to colonize other organs.
Therefore, if we carry out a blood test to detect a potential infection, couldn't we do the same to determine if there are tumor cells with metastatic capacity in the blood? That is, a liquid biopsy. The term liquid biopsy is not new in its general definition, but it is new with regard to its association with so-called solid tumors: lung, breast, colon, and prostate cancer, among others. However, it cannot be applied to leukemias, as it is a cancer of the blood. A liquid biopsy in cancer has the same objective as a routine blood test that we perform to measure, for example, cholesterol levels, by quantifying HDL and LDL proteins, only, instead of determining those proteins , we measure markers associated with cancer. That is, a liquid biopsy is the determination of markers associated with cancer in a body fluid (for example, blood) and of course in a non-invasive way, so that it can be performed routinely and as many times as necessary (as we do with blood glucose detection for diabetics).
IT IS NOT THE TUMOR THAT KILLS THE PATIENT, BUT THE ABILITY OF THEIR CELLS TO EXPAND IT
But… not all markers are equally specific and reliable, and not all markers are expressed the same in each of us. Our barcode, remember? Let's take an example by going back to Ernesto and Manuel -both diagnosed with the same type of lung cancer- and both are treated with the same drug because they both have "the same" disease. However, one of them, Ernesto, responds to treatment while in Manuel the disease continues its aggressive course. It seems that "coffee for everyone" does not work. What logic has that being the "same" disease one responds to treatment and another does not? The difference is that Ernesto's tumor cells express a marker against which the drug is directed, while Manuel's cells do not express it and the treatment “tickles his tumor cells”. The consequences may go beyond the lack of response to treatment, since Manuel is undergoing very toxic and excessively expensive treatments. Therefore, the lack of foresight in the determination of the marker has clinical and also economic consequences.
We therefore need to identify what the tumor cells of each patient are like, that is, the presence or not of that potential molecule (marker) and for that our surgeons and pathologists are present who remove the tumor on the one hand and analyze the tumor on the other, classifying it so that our oncologists administer the appropriate treatment (precision medicine). Of course, as long as there is the possibility of removing the tumor mass by surgery, but ... what if it is not possible to obtain a sample of the tumor mass? Perhaps the answer is in the blood… To be continued.