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Full genome sequencing will allow treating cancer individually
Ksenia Vasilyeva, Vesti
The human genome is "written" in the DNA molecule in the form of "letters" – blocks that scientists call nucleotides. Each such "brick" has its own international name, which is shortened to the first letter for the convenience of genetics.
So, these organic compounds are designated by the letters A (adenine), C (cytosine), G (guanine) and T (thymine). Usually nucleotides are grouped into pairs in a strictly defined way. However, sometimes the "spelling" of DNA makes mistakes and, for example, in place of A becomes G.
These changes, or mutations, can be spontaneous or occur under the influence of adverse factors. So, tobacco smoke, ultraviolet radiation, and various chemicals can become the culprit of the "breakdown". Each mutation leaves a certain imprint in the DNA.
Cells, dividing and multiplying, reproduce exact copies of their DNA, so any "spelling mistakes" 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 the University of Cambridge, working under the leadership of Serena Nik-Zainal, proposed to use the sequencing of the genome of a cancerous tumor to combat such diseases.
This method allows you to "read" the entire genetic scheme of a cancer cell. If we compare the data obtained with the genome of healthy cells of a sick person, we can see exactly 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 all women with breast cancer have been participating since 2010. Accordingly, doctors have collected a large database of the results of examinations and treatment of their patients.
Using this extensive data, the researchers performed a complete sequencing of the genome of tumor cells of 254 women who were found to have so-called triple negative breast cancer.
Scientists chose this variant of the disease for a reason. Triple negative cancer is one of the most aggressive tumors with the worst prognosis of survival.
The disease 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 the BRCA1/BRCA2 type of cancer, for which a relatively new class of drugs – PARP inhibitors - is considered the best treatment for today.
After processing the genome sequencing data of the patients' tumors, the algorithm divided all the women into three groups, assigning a high, medium or low rating.
High suggested that women are most likely to have a BRCA1/BRCA2-associated tumor. Their response to the use of existing drugs and forecasts for recovery were the best.
Surprisingly, the group that was assigned an intermediate number of points and which should have responded relatively well to modern medications showed the worst response to the funds available in the oncologists' arsenal.
This means that the tumors in these patients were probably provoked by mutations other than BRCA1/BRCA2 and required other therapeutic approaches.
And this is very valuable information. The "reading" of the genome of tumors of patients in this category gave experts a hint which 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, which was assigned a low rating by artificial intelligence based on sequencing results, also responded to treatment in a far from 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 checkpoint inhibitors.
According to the researchers, sequencing the genome of tumors helps to accurately determine the degree of "responsiveness" of cancer to the planned treatment. It is especially important to have such information when starting treatment for women with triple negative cancer, which is still considered a difficult-to-treat disease.
But the most significant, according to scientists, is the fact that sequencing the genome of cancer cells helps to find out what is happening in tumors that are poorly amenable to existing cancer therapy. Understanding this process will help to develop new effective ways to overcome a dangerous disease.
By the way, the progress in sequencing technologies is very impressive. A complete analysis of the tumor genome today can be carried out in just 24 hours. Oncologists need another 24-48 hours to analyze the data obtained.
Therefore, today it is quite realistic to make sequencing a routine research method in order to assess the course of each patient's illness and develop an individual most effective treatment plan.
The proposed method, the researchers believe, opens the way to getting rid of even the most complex and resistant to therapy malignancies.
"Sequencing gives us a complete picture of the cancer genome. It reveals many things that we couldn't see before because we weren't even looking for them. A complete "map" of each patient's cancer genome helps to understand what caused the tumor in each case and to treat each individual more effectively," explains Serena Nick–Zainal in a university press release Study highlights potential of whole genome sequencing to enable personalized cancer treatment.
The results of the study by an international team of scientists are published in the prestigious scientific publication Nature Medicine (Staaf et al., Whole-genome sequencing of triple-negative breast cancers in a population-based clinical study).
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