Advances with individualized therapies do not stop: immunotherapy, CAR-T… Now, Europe is on the verge of having the first drug based on CRISPR, a technology that is the result of genetic editing and promises to be effective against two blood diseases.
Medicine tailored to the patient. What was once an entelechy, now turns out to be a reality in a state of expansion. For example, thanks to the discovery of the HER2 biomarkerToday, in clinical practice, there is a group of women with early-stage cancer who benefit from a very specific treatment, with which the chances of eliminating the tumor are doubled. Before being able to give this surname to the tumor, this part of the population received the stipulated treatment, which “not only had no benefits, but also gave them side effects. It was not effective at all,” says Carlos Sisternas, director of the Spanish Federation of Health Technology Companies (Fenin) of Catalonia.
This is what personalized medicine is about. It consists of designing a specific menu of medications, «according to the individual characteristics of each patient». That is one of the great challenges of medicine: to achieve more effective individualized drugs, with fewer side effects and capable of increasing the survival of people with metastases, improving their quality of life and saving the health system up to 25,000 euros per patient, according to estimate some work carried out by the American National Institutes of Health (NIH).
For this, says Sisternas, “technologies for molecular diagnosis and massive sequencing panels, in addition to the many equipment in clinical analysis and pathological anatomy laboratories, are key.” Thanks to them, Researchers around the world have been studying the genome for more than two decades to learn more and more about alterations that occur in different diseases. In this way, work can be done on the development of drugs that act selectively, inhibiting the damaged gene and, therefore, interfering with the progression of the pathology and the survival of the affected person.
It was in 2003 when, after many years of effort, the essential sequence of our DNA was deciphered for the first time. It was a true milestone, although it did not bring together all the information of the genome. There were some gaps that, little by little and with the technological improvements that have been taking place, are being dissolved.
In the study of this cartography, genetic alterations associated with different diseases are discovered, which in addition to Improving the differential diagnosis makes a big difference in the patient’s prognosis. Returning to the example of HER2 positive breast cancer, based on the analysis of the tumor sample, if the medical team identifies said genetic alteration in HER2 (which occurs in 18%-20% of cases), the outlook improves. notably. Treatment directed against HER2 (anti-HER2 therapy) produces virtually no side effects.
He too Lung cancer shows great progress thanks to personalized medicine. Around 15% of those affected, generally non-smokers, harbor alterations in the EGFR -Epidermal Growth Factor- and ALK genes. In a standardized manner, the possible presence of these mutations in metastatic patients is analyzed. When they are positive, the indicated treatment would not be chemotherapy but rather specific inhibitors of these alterations. Thus, the therapy manages to block the functioning of tumor cells and, therefore, prevents the growth of the lesion. With chemo, 40% of patients respond and the average survival is 12 months.
Paradigm shift
Actually, the door opened with the chronic myeloid leukemia. According to Ismael Buño, scientific director of the Gregorio Marañón Health Research Institute (IiSGM), “it was the first tumor in which a causative genetic alteration was found (the Philadelphia chromosome was discovered in 1960 by two scientists from this American city: Peter Nowell and David Hungerdorf) and the first in which a specific inhibitor was developed as a treatment. This is what is known as therapies directed at molecular targets.
If previously patients with this disease were condemned to die, now their quality of life is practically the same as that of the rest of the healthy population of their age. “This advance marked the path of what we should do, the beginning of the new medicine,” says Buño. “Personalized medicine comes from the world of genomics, it was born with biomarkers.”
The concept of genetic biomarker It refers to a fraction of DNA, which is what indicates the characteristics of each individual. Today, its use is one of the most important clinical tools in precision medicine. It is true that especially in oncological diseases, but also in the diagnosis and treatment of rare diseases.
It is worth remembering the case of Judy Perkins, a woman with metastatic breast cancer whom the doctors considered hopeless. With different tumors spreading throughout her body, Perkins underwent an experimental treatment at the National Institute of Health in Bethesda (Maryland, USA) based on T cell immunotherapy, a highly personalized therapy. The researchers sequenced the DNA and RNA from one of her tumors, as well as normal tissue, with the goal of checking which mutations were unique to her cancer. They identified 62 different mutations in their tumor cells.
Then, through complex engineering work, they selected the most powerful T lymphocytes from Perkins’ own immune system to grow them in large quantities in the laboratory and direct them towards the proteins caused by the mutated gene and expressed on the surface of the cells. malignant. About 90,000 million immune cells were those that the patient received through an injection, along with two other drugs: interleukin and pembrolizumab. What this medication does is prevent the immune system from falling asleep and acting against tumor cells. Although this effect had not yielded many results in breast cancer, the clinical trial worked. After a week, the tumor shrank and experts began to talk about remission.
The immunotherapy It takes advantage of the patient’s own immune system to fight the disease. Another of the great advances in personalized medicine is based on this premise: CAR-T. They consist of extracting lymphocytes to genetically modify them in order to reintroduce them into the patient so that they are capable of recognizing and attacking cancer cells. These therapies have achieved important results in hematological tumors and are increasingly expanding their effects. Positive response rates are already beginning to be published in solids, such as HER2-positive breast cancer.
As to CRISPR, at the end of 2023, all the media echoed the recommendation by the European Medicines Agency to authorize a treatment based on this genome editing therapy. Its name: Casgevy, effective against sickle cell anemia and beta thalassemia, two potentially lethal blood diseases. The drug already had the approval of the regulatory agencies of the United Kingdom and the United States. It is expected that the European Commission will soon give the green light to its commercialization.
The great revolution of CRISPR lies in its ability to correct errors in DNA. It is a genetic engineering technique that allows the genome of any cell to be corrected and edited. Thanks to this tool, researchers Jennifer Dounda and Emmanuelle Charpentier won the Nobel Prize in Chemistry in 2020.
They are known as the molecular scissors, because they act by cutting and gluing fractions of genetic material. This genetic cut-and-paste has shown promise as a therapeutic approach to treating rare inherited diseases. However, most gene editing strategies focus on correcting specific mutations that only occur in a small group of patients before the onset of the disease.
At the beginning of last year, a study published in the journal Science found good results in a more common pathology, in cardiology, specifically, in the repair of ischemia-reperfusion injuries, which cause other ailments such as myocardial infarction. The experiment modified mouse hearts, so there is still time to expand the applications of this genetic technique.
