Complete genome sequencing allows you to treat cancer individually

UNITED STATES, WASHINGTON (OBSERVATORY) — The human genome is “registered” in the DNA molecule in the form of “letters” – blocks that scientists call nucleotides. Each such “brick” has its own international name, which for the convenience of genetics is reduced to the first letter.

So, these organic compounds are denoted by the letters A (adenine), C (cytosine), G (guanine) and T (thymine). Usually nucleotides are grouped in pairs in a strictly defined way. However, sometimes the “spelling” of DNA makes mistakes and, for example, G becomes G.

These changes or mutations can be spontaneous or occur under the influence of adverse factors. So, the culprit of the “breakdown” may be tobacco smoke , and ultraviolet radiation , and various chemicals. Each mutation leaves a definite imprint on the DNA.

Cells, dividing and multiplying, reproduce exact copies of their DNA, so any “spelling errors” in it will be exactly repeated and passed on. Over time, the number of such problems accumulates. This can lead, among other things, to uncontrolled cell growth, in other words, the development of a tumor.

A group of scientists from Cambridge University, led by Serena Nik-Zainal, proposed to use for the fight against such diseases sequencing of the genome of the cancerous tumor.

This method allows you to “read” the entire genetic scheme of a cancer cell. If we compare the obtained data with the genome of healthy cells of a sick person, we can see how the DNA mutated and, based on this, develop an optimal treatment strategy.

To find out how applicable and useful this method is in everyday clinical practice, researchers from Cambridge teamed up with colleagues from Sweden.

The fact is that Swedish oncologists are conducting a nationwide project called SCAN-B, in which since 2010 all women with breast cancer have been participating. Accordingly, doctors have compiled a large database of examination results and treatment of their patients.

Using these extensive data, the researchers performed a complete sequencing of the genome of the tumor cells of 254 women in whom the so-called triple negative breast cancer was detected .

Scientists have chosen this option of the disease for a reason. Triple negative cancer is one of the most aggressive tumors with the worst prognosis of survival.

The ailment got its name because such formations lack three main target molecules (receptors), which are usually affected by drugs.

After completing the sequencing, the researchers applied a machine learning algorithm called HRDetect, which geneticists had previously developed to identify tumors with characteristic “genetic signatures” caused by mutations in the BRCA1 or BRCA2 genes.

It is worth explaining that the algorithm was developed specifically for these two genes because the presence of any of them increases the risk of developing breast cancer .

Thus, HRDetect can predict the probability of exactly BRCA1 / BRCA2 type of cancer, for which a relatively new class of drugs – PARP inhibitors is considered the best treatment today.

Having processed the sequencing data for the patient’s tumor genomes, the algorithm divided all women into three groups, assigning a high, medium or low rating.

High suggested that women most likely have a BRCA1 / BRCA2-associated tumor. Their response to taking existing drugs and their predictions for recovery were the best.

Surprisingly, the group, which was assigned an intermediate number of points and which should have responded relatively well to modern medicines, showed the worst response to the funds available in the arsenal of oncologists.

This means that the tumors in these patients were probably triggered by mutations other than BRCA1 / BRCA2 and required other therapeutic approaches.

And this is very valuable information. “Reading” the genome of the tumors of patients in this category gave specialists a hint what mechanisms lead to the development of their type of cancer. This means that it will be easier for experts to develop new effective drugs and treatment regimens.

The last group, to which artificial intelligence assigned a low rating by sequencing, also did not respond to treatment in the best way, that is, their cancer was also caused by other DNA damage.

However, the genome of the neoplasms of these participants indicated biological changes that could potentially be “attacked” by both existing drugs and drugs undergoing clinical trials. These include, for example, immune control point inhibitors (Vesti.Nauka talked in detail about this class of drugs).

According to the researchers, the sequencing of the tumor genome helps to accurately determine the degree of “response” of cancer to the planned treatment. It is especially important to have this information when starting treatment for women with triple negative cancer, which is still considered an intractable disease.

But the most significant, according to scientists, is the fact that sequencing of the genome of cancer cells helps to find out what happens in tumors that are poorly suited to existing anti-cancer therapy. Understanding this process will help develop new effective ways to overcome a dangerous disease.

By the way, progress in sequencing technologies is quite impressive. A complete analysis of the tumor genome today can be done in just 24 hours. Oncologists need another 24-48 hours to analyze the data.

Therefore, today it is quite realistic to do sequencing with a routine research method in order to assess the course of the disease of each patient and develop an individual most effective treatment plan.

The proposed method, the researchers believe, paves the way to getting rid of even the most complex and therapy-resistant malignancies.

“Sequencing gives us a complete picture of the cancer genome. It reveals many things that we could not see earlier, because we did not even look for them. A complete” map “of the cancer genome of each patient helps to understand what caused the tumor in each case and is more effective treat every individual, “Serena Nik-Zainal explains in a university press release.

The research results of an international team of scientists are published in the prestigious scientific publication Nature Medicine.

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