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Repair DNA to cure cancer and distortions

Report. Over the last ten years, biomedical scientists from universities, institutes and private laboratories have developed various techniques to correct errors and damage caused by DNA molecules during copying. In 2018, Mexico was the first country in the world that approved the use of a new type of therapy called "precision medicine" against cancer of chronic lymphatic leukemia

DNA or deoxyribonucleic acid is a molecule found in the nucleus of every cell of living things, plants or animals. Each time a cell is copied for reproduction and before it dies, the DNA is copied to the original cell and transferred to a new cell. But when there are errors in copying can be serious and even deadly diseases, such as different types of cancer.

Over the last ten years, biomedical scientists from universities, institutes and private laboratories have developed various techniques to correct errors and damage caused by DNA molecules during copying.

We must remember that DNA is a molecule similar to two long threads connected with wires, which makes them look like a painter's stairs with thousands of steps. When the step is broken from the bank or when the step is in a different order from the original – which is known as a translocation – problems arise. Using analogy, we can say that DNA is a thread as long as a golf club, but thinner than hair, and each cell has the same in the nucleus.

Today, thanks to work at the particle level, a new branch of pharmacology has opened up called High Precision Medicine, which already produces medicines available in hospitals in various parts of the world, including Mexico, to stop the proliferation of cancer cells in the blood and lungs, including tissues .

Another new DNA repair technique that can be considered "revolutionary" without exaggeration is the edition of genes using biochemical scissors called CRISPR-Cas9, which has already been used in laboratories in China, the United States and Korea, to repair genomic damage that causes lung cancer and heart defects in human embryos. This technique is not yet commercially available, but its tests are rapidly progressing.

In 2015, the Swedish Academy of Sciences awarded the Nobel Prize in Medicine to three scientists who separately explained how cells work at the molecular level to repair DNA damage. They showed in their works that every day there are processes to repair damage inside the human body, as well as in the body of all plants and animals. However, when the repair mechanisms fail, various diseases appear.

These pioneers in the discovery of DNA repair mechanisms are Tomas Lindahl, Paul Modrich and Aziz Sancar. His studies began decades earlier, but now his products are starting to benefit people.

PRECISION AGAINST LEUKEMIAIn 2018, Mexico was the first country in the world to approve the use of a new type of therapy called "precision medicine" against cancer of chronic lymphatic leukemia (CLL).

The new treatment, which was approved by the Mexican authorities in the last week of May and the US government a week later, on June 7, is an innovation because it corrects the molecular error that prevents the death of cancer cells. By acting on a specific structure or "sensor" of diseased cells, treatment is considered a precise drug.

Authorization for the use of this treatment in Mexico was issued by the Federal Commission for Sanitary Threat Protection (Cofepris) and granted to the AbbVie Mexico biotechnology laboratory, which carried out an international study – named MURANO – to support the new treatment.

Chronic lymphocytic leukemia (CLL) is a type of slow-growing cancer in the bone marrow and in the blood where the types of white blood cells called lymphocytes become cancerous and multiply incorrectly. It is one of the most common types of leukemia in adults, accounting for 30% of leukemias with a predominance of twice as high in men as in women.

By causing the death of diseased cells, it replaces chemotherapy in the elimination of cancer cells, which has negative effects. This therapy was presented in Chicago during the meeting of the American Society of Oncology and Oncology (ASCO), which ended on June 5.

Although it sounds strange, the basic problem with different types of cancer is that the cells appear that they never die. Every healthy cell has a lifespan and, after completing its cycles, birth, growth and reproduction must die, but the cancer cells have a genetic information error in which the instructions for dying are gone.

In this way, when the cell does not die, that is, when its process called apoptosis does not occur, it starts to reproduce and large accumulations or tumors arise. When cells that do not die pass through the organ and disperse or overflow through different parts of the body, so-called metastases start.

Precision medicine aims to correct molecular error that prevents cell death and attempts to restore original instructions regarding apoptosis or cell death after completing a full life cycle.

In June, Dr. Eduardo Edmundo Reynoso Gómez, a hematologist at the Español de México Hospital, explained Chronicle that the new treatment helps people with CLL live longer without getting worse, compared to standard chemo-immunotherapy, which offers deep remissions and fixed schedules, but with more toxicity.

BRAKE LUNG CANCER. Another area in which precision medicine already provides benefits within the population is to extend the lives of patients who have been diagnosed with incurable lung cancer who previously survived only two to four months. and now you can treat this type of medicine that corrects changes caused by errors in DNA copying, and thus helps increase survival to an average of 18 months, but with documented cases in which incurable patients have survived three and a half or four years.

Some of these cases have occurred in the same geographical region in which Mexico is located, as demonstrated by the oncologists in Argentina and Costa Rica during the Pfizer Latin American seminar on lung cancer held this month in Buenos Aires.

There the message stressed that one must be optimistic in the fight against lung cancer, but it should also be understood that there is no medicine for all patients and that in Latin America, most patients are diagnosed when their lung cancer is incurable.

"The strongest change that has brought relief to these patients is that in the last four years, with the consent and use of a new class of drugs called precision medicines, genetic mutations can be improved by causing a tumor in the lungs," he explained. Chronicle Dr Luis Corrales, oncologist at the Cancer Research Center, San José, Costa Rica.

"Mutations occur when certain genes change position or change in chromosomes (which are found in the nucleus of each cell.) When these changes affect some of the proteins present in the cell membrane and that act as receptors for biochemical orders. They are "turned on" and are sending signals so that cells can reproduce without stopping, so tumors arise, which is why there are new drugs that correct the genetic mutation and interrupt these disordered signals that cause cells to reproduce without control, "said a Costa Rican expert.

The most frequent key message during the medical meeting was that "before chemotherapy is given to a patient with lung cancer, a molecular test is required" because there are patients who are not treated with chemotherapy and do not harm them. Although there are patients with lung cancer who can use drugs that correct genetic changes without the use of standard chemotherapy.

"We are experiencing a change in strategy or treatment paradigm," said Dr. Diego Kaen, head of oncology at the university hospital of the National University of La Rioja in Argentina.

"The treatments most commonly used to correct mutations are those that affect the activity of the two proteins found in the cell membrane and are called EGFR and ALK +, both of which affect cell reproduction, and if they are corrected, the tumor shrinks and the patient's quality of life significantly improves, "said Dr. Kaen, who agreed that this change began in 2014.

"There are currently 3 and a half year patients and four years with lung cancer, with an average survival of 18 months, but before they survived only four months, the doctors simply sent them home to repair their legal and family matters before they died" – said the same doctor who is in charge of clinical trials at the Oncológico Center Riojano Integral (CORI).

Gene editing. In addition to the High Precision Medicine, in the last two years there have been spectacular news in the world of basic science related to another technique for fixing errors in DNA, which has been called the "gene edition".

This technology can be explained if we think about scissors programmed to cut in a specific part of the DNA molecule, where we want to make a correction or edit. Scissors are molecules called CRISPR-Cas9.

In this issue of the gene, whatever is wrong, is cut off, but nothing external is blocked, because it happens that after the cut the DNA repair reaction is activated in the specific place where the intervention was made.

A new tool for the 'edition' of genomes named CRISPR-Cas9 was successfully tested on October 28, 20016. In China, where a patient with lung cancer was successfully treated with edited cells.

At that time, the commercial landscape of CRISPR-Cas9 therapy was uncertain due to the legal battle for US patent rights regarding the gene editing technique. The problem is stuck in the United States Patent and Trademark Office, which is responsible for determining who invented the technique for the first time.

However, the high benefits that this technology promises continue to drive the laboratory, and a year later, on August 2, 2017. In a historical fact for science, scientists from the United States, China and South Korea have been able to correct for the first time in human embryos a hereditary disease, thanks to using the same genetic editing technique.

Thanks to their work, they improved the mutation of a gene that causes a pathology called hypertrophic cardiomyopathy, which suffers from one in 500 people and is the most common cause of sudden death of athletes.

In order to carry out experiments, zygotes were made by fertilizing healthy oocytes with semen from a donor carrying a mutation in the MYBPC3 gene that causes the disease.


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