Medicine’s “magic bullet” – personalization

Medicine adapted to the patient. What was once entelechy now appears to be a reality in a state of expansion. For example, thanks to the discovery of the HER2 biomarker.In clinical practice today, there is a group of women with early-stage cancer who benefit from very specific treatments that double their chances of eliminating the tumor. Before allowing the tumor to give this name, this part of the population received prescribed treatment, which “not only had no benefit, but also had side effects. It was completely ineffective,” says Carlos Cisternas, director of the Spanish Federation of Health Technology Companies (Fenin) of Catalonia.

This is what personalized medicine is. It consists in developing a specific menu of medications, “taking into account the individual characteristics of each patient” This is one of medicine’s greatest challenges: to develop more effective, individualized drugs with fewer side effects that can increase the survival rate of people with metastatic disease, improve their quality of life and save the healthcare system up to 25,000 euros per patient, according to some work carried out by the American National Institutes. Health (NIH).

To achieve this, says Cisternas, “molecular diagnostic technologies and mass sequencing panels are key, as well as numerous equipment in the clinical analysis and pathology laboratories.” Thanks to them, Researchers around the world have been studying the genome for more than two decades to learn more and more about the changes. which occur in various diseases. In this way, it is possible to work on the development of drugs that act selectively, inhibiting the damaged gene and, therefore, preventing the progression of pathology and the survival of the sick person.

It was in 2003 when, after many years of effort, the basic sequence of our DNA was first deciphered. This was quite a milestone, although it did not integrate all the information in the genome. There were some gaps that are being eliminated little by little and with ongoing technological improvements.

When studying this mapping, genetic changes are found that are associated with various diseases that, in addition to Improving the differential diagnosis is of great importance for the patient’s prognosis.. Returning to the example of HER2-positive breast cancer, based on analysis of a tumor sample, if the medical team identifies a specified genetic change in HER2 (which occurs in 18-20% of cases), the prognosis is markedly improved. Treatments directed against HER2 (anti-HER2 therapy) cause few side effects.

Him too Lung cancer shows great progress thanks to personalized medicine. About 15% of patients, usually non-smokers, have changes in the EGFR (epidermal growth factor) and ALK genes. The possible presence of these mutations in metastatic patients is routinely assessed. If they are positive, the indicated treatment will not be chemotherapy, but rather specific inhibitors of these changes. Thus, the therapy manages to block the functioning of tumor cells and, therefore, prevent the growth of the lesion. 40% of patients respond to chemotherapy, and the median survival is 12 months.

Paradigm Shift

In fact, the door opened with chronic myeloid leukemia. According to Ismael Buño, scientific director of the Gregorio Marañon Health Research Institute (IiSGM), “this was the first tumor in which a causative genetic change was discovered (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 the so-called therapy aimed at molecular targets.

If previously patients with this disease were doomed to death, now their quality of life is almost the same as that of the rest of the healthy population of their age. “This achievement marked the way of what we should be doing, the beginning of a new medicine,” says Bugno. “Personalized medicine came from the world of genomics, it was born with biomarkers.”

The concept of something genetic biomarker This refers to the fraction of DNA that indicates the characteristics of each person. Today, its use is one of the most important clinical tools in precision medicine. This is true, especially in cancer, but also in the diagnosis and treatment of rare diseases.

It is worth remembering the case Judy Perkins, woman with metastatic breast cancer which doctors considered hopeless. As various tumors spread throughout his body, Perkins underwent experimental treatment at the National Institutes of Health in Bethesda, Maryland, USA, based on T cell immunotherapy, highly personalized therapy. The researchers sequenced the DNA and RNA of one of her tumors, as well as normal tissue, to test which mutations were unique to her cancer. They identified 62 different mutations in their tumor cells.

Then, through complex engineering, they selected the most powerful T cells from Perkins’s own immune system to grow in large numbers in the laboratory and target proteins caused by the mutated gene and expressed on the surface of the malignant cells. . About 90,000 million immune cells were those that the patient received through an injection along with two other drugs: interleukin and pembrolizumab. This medicine prevents the immune system from going to sleep and attacking tumor cells. Although this effect didn’t show much benefit in breast cancer, the clinical trial worked. A week later, the tumor shrank and experts began to talk about remission.

immunotherapy It uses the patient’s own immune system to fight the disease. Another of the great advances in personalized medicine is based on this premise: AUTOMOBILE-T. They involve extracting lymphocytes and genetically modifying them to reintroduce them to the patient so that they are able to recognize and attack cancer cells. These treatments have achieved important results in hematological tumors and are increasingly expanding their effects. Data on positive responses to solid substances such as HER2-positive breast cancer are already beginning to be published.

Relatively CRISPRAt the end of 2023, the entire media supported the European Medicines Agency’s recommendation to authorize treatments based on this genome editing therapy. Its name: Kasgevy, is effective against sickle cell anemia and beta thalassemia, two potentially fatal blood diseases. The drug has already received regulatory approval in the UK and US. The European Commission is expected to give the go-ahead for its commercialization soon.

The great revolution of CRISPR lies in its ability to correct errors in DNA. This is a genetic engineering method that allows you to correct and edit the genome of any cell. Thanks to this instrument, researchers Jennifer Dunda and Emmanuel Charpentier received the Nobel Prize in Chemistry in 2020.

They are known as molecular scissors because they work by cutting and gluing together pieces of genetic material.. This cut-and-paste genetic technique has shown promise as a therapeutic approach to treat rare inherited diseases. However, most gene editing strategies are aimed at correcting specific mutations that occur only in a small group of patients before the onset of the disease.

Early last year, a study published in the journal Science found good results for a more common pathology in cardiology, specifically repairing ischemia-reperfusion injury, which causes other diseases such as myocardial infarction. The experiment modified the hearts of mice, so there is still time to expand the use of this genetic method.