Monday , June 27 2022

Repair DNA to cure cancer and malformations


Report. Over the past ten years, biomedical researchers from universities, institutes and private laboratories have developed various techniques that try to correct the errors and damage suffered by DNA molecules when copied. In 2018, Mexico was the first country in the world to approve the use of a new type of therapy called "precision medicine" against white blood cell cancer of the type of chronic lymphocytic leukemia

DNA or deoxyribonucleic acid is a molecule that is in the nucleus of every cell of living beings, plants or animals. Every time a cell is copied to reproduce and before it dies, the DNA is copied into the original cell and moved to the new cell. But when there are mistakes in copying can be serious and even deadly diseases, such as different types of cancer.

Over the past ten years, biomedical researchers from universities, institutes and private laboratories have developed various techniques that try to correct the errors and damage suffered by DNA molecules when copied.

We have to remember that DNA is a molecule similar to the two long threads of binding, which makes them look like a ladder's scale with thousands of steps. When a step is broken from a bank or when a step is in a different order than the original – what is called translocation – problems arise. Using an analogy, we can say that DNA is a thread as long as a golf club, but thinner than a hair and every cell has an equal within its core.

Today, working with molecules has opened a new field of pharmacology called High Precision Medicine, which has already generated drugs available in hospitals in different parts of the world, including Mexico, to stop the multiplication of cancer cells in the blood and lungs, among others tissues.

Another new DNA repair technique, which can be considered "revolutionary" without exaggeration, is gene editing by means of biochemical scissors called CRISPR-Cas9, which has already been used in laboratories in China, the United States and Korea, to repair the damage of the genome that causes lung cancer and cardiac malformations in human embryos. This technique is not yet commercially available, but its tests are advancing rapidly.

In 2015, the Swedish Academy of Sciences awarded the Nobel Prize for Medicine to three researchers who separately explained how cells function at the molecular level to repair DNA damage. They have shown with their work that every day there are processes of repairing the damage inside the human body as well as inside the body of all plants and animals. However, when the repair mechanisms fail, different diseases occur.

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

PRECISION AGAINST LEUKEMIA. In 2018, Mexico was the first country in the world to approve the use of a new type of therapy called "Precision Medicine" against white blood cell cancer such as chronic lymphocytic leukemia (CLL).

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

Authorization to use this treatment in Mexico was issued by the Federal Commission for the Protection against Health Risks (Cofepris) and granted to AbbVie Mexico biotechnology laboratory, which has conducted a multinational study called MURANO to support the new treatment.

Chronic Lymphocytic Leukemia (CLL) is a slow type of cancer in bone marrow and blood, where the types of white blood cells called lymphocytes become cancerous and abnormally multiply. It is one of the most common types of leukemia in adults, accounting for 30% of leukemia, with a double prevalence in males than in women.

By causing the death of diseased cells, it replaces chemotherapy in the eradication of cancer cells, which has adverse effects. This therapy was presented in Chicago at the American Society for Cancer and Oncology (ASCO) meeting, which ended on June 5th.

Although it sounds strange, the problem behind the different types of cancer is that there are cells that never die. Every healthy cell has a lifetime, and after the end of the birth cycle, growth and reproduction have to die, but cancer cells have a genetic information error where the instructions to die have disappeared.

In this way, when a cell does not die, that is, when its process called apoptosis does not occur, large spikes or tumors begin to replicate and form. When those cells that do not die die, pass through an organ and disperse or ignite through different parts of the body, start so-called metastasis.

Precision medicine tries to correct the molecular error that prevents cell death and tries to return the initial instructions of apoptosis or cell death after a complete life cycle.

In June, Dr. Eduardo Edmundo Reynoso Gómez, a hematology specialist at Español de México Hospital, explained chronicle that the new treatment helps people with CLL to live longer without aggravating the disease compared to standard chemo-immunotherapy that provides profound remissions and fixed programs but with greater toxicity.

FRONT BRAKE BRAKES. Another area where high-precision medicine already offers benefits to the population is to extend the life span of patients who have been diagnosed with incurable lung cancer that previously only survived between two and four months and can now be treated with this type of medicines to correct the changes caused by errors in DNA copying and thus to help increase survival to an average of 18 months but with documented cases where incurable patients survived three and a half or four years.

Some of these cases occurred in the same geographical region as Mexico, as presented by oncologists in Argentina and Costa Rica at the Pfizer Latin American Seminar on Lung Cancer, which took place this month in Buenos Aires.

There, the message that he has to be optimistic in the fight against lung cancer has been emphasized, but it must 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 already incurable.

The most powerful change that has been made to help these patients is that over the last four years with the approval and use of a new group of treatments called precision drugs, genetic mutations can be corrected that cause the appearance of tumors in the lungs, he explained chronicle Dr. Luis Corrales, an oncologist at the Center for Cancer Research and Management, San José, Costa Rica.

Mutations occur when some genes change position or are altered inside the chromosomes (which are in the nucleus of each cell). When these changes affect some proteins that exist in the membrane of each cell and which function as receptors of biochemical orders. If these proteins are bad, they remain "on" and send signals for the cells to reproduce without stopping. This is how the tumors are formed. That's why there are new drugs that correct the genetic mutation and interrupt disorderly signals that call cells to reproduce without control, "the Costa Rican expert said.

The most important key message in the medical meeting was that "before giving chemotherapy to a lung cancer patient, a molecular test should be performed" 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 using standard chemotherapy.

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

The most used treatments to correct mutations are those that influence the activity of two proteins that are in the cell membrane and are called EGFR and ALK +. Both affect cell multiplication, and if these are corrected, the tumor shrinks and the quality of the patient's life improves a lot, "Dr. Kaen said, who agreed that this change began in 2014.

Currently, there are patients with three and a half years and four years of life with lung cancer. The average survival is 18 months, but before they only lived 4 months and the doctors sent home to establish their legal and family things before they died, "said the same doctor, head of clinical research at the Oncológico Riojano Integral Center (CORI).

Genetic editing. In addition to high-precision medicine, in the past two years, spectacular news has come up in the world of fundamental science about another DNA-repair technique called "genetic editing."

This technology can be explained if we are thinking of scissors scheduled to cut a particular part of the DNA molecule where we want to do the correction or editing. These scissors are molecules called CRISPR-Cas9.

In this edition of the gene, what is wrong is cut but nothing external is blocked because what happens is that when cutting is done, a DNA repair response is activated in the specific location where it was done intervention.

The new "publishing" genome tool, called CRISPR-Cas9, was successfully tested in China on October 28, 20016, where a lung cancer patient was successfully treated with edited cells.

At that time, the commercial landscape of CRISPR-Cas9 therapies was uncertain because of a legal jolt over American patent rights over gene editing techniques. The issue is blocked in the United States Patent and Trademark Office, which has an obligation to determine who invented the technique for the first time.

However, the high benefits that this promise of technology continued to lead in the lab, and a year later on August 2, 2017, in a historical fact for science, researchers in the United States, China and Korea South managed to first correct the hereditary disease in human embryos due to the use of the same genetic editing technique.

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

To perform the experiments, the zygotes were produced by fertilizing healthy oocytes with sperm from a donor that carries a mutation in the MYBPC3 gene that causes the disease.


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