NEW Molecular oncology. Molecular oncology. Highly differentiated thyroid cancer

As a result of the progress of new scientific areas of molecular biology, molecular genetics and genetic engineering a huge step forward has been made, which now allows us to ask nature questions that were previously impossible to ask. It is about understanding the most fundamental foundations of such phenomena as cell division and differentiation, as well as the causes of the mechanism of their violations.

In a specific application to one of the most topical and exciting problems facing humanity - the problem of malignant tumors - we can talk about the appearance new science- molecular oncology. Her striking success in the field of studying the molecular mechanisms of oncogenesis and the molecular basis of the cancer phenotype is associated with the use of unique research methods inherent in her.

The book "Molecular Oncology", which is being published and is offered to readers, is devoted to summing up the first results and presenting the achievements of this young science. It clearly traces the continuity of the basic principles and postulates of classical theoretical oncology, primarily in the main issues: the polyetiology of the onset of tumors and the multi-stage nature of this process.

However, solutions are already given at another level of organization of living matter - the molecular one. This book- the first and only so far in our country. It was written by authors who are directly and actively working in this field, which predetermined the depth of understanding of the given specific facts and the constructiveness of generalizations. The idea of ​​the universality of the molecular mechanisms of oncogenesis runs throughout the book.

This idea follows naturally from the analysis carried out by the authors latest research the main types of carcinogenesis: chemical, physical, biological, the basis of which, as the authors convincingly show, is one and can be expressed in fundamentally general molecular terms.

Separate chapters are devoted to each of these types of oncogenesis. Chapter 1 turns the reader to the origins of theoretical oncology, to its classic studies of the beginning of this century. Chapters 2 and 3 are devoted to the molecular mechanisms of chemical and viral carcinogenesis, respectively.

The first three chapters mentioned logically precede the final chapters 4 and 5, the true core of the book.

It is in these chapters that facts and ideas are presented in a concentrated form, symbolizing the essence and spirit of modern theoretical oncology - molecular oncology. Her achievements inspire confidence in the final victory of the human mind over a serious illness.

"Molecular Oncology"
I.F. Seitz, P.G. Knyazev

To a critically thinking observer, modern theoretical oncology may appear to be a flowering tree, but not a fruitful one. Such an impression is to some extent justified and is due to a clear imbalance of huge intellectual efforts and material investments, on the one hand, and modest practical outputs, on the other. Still remain unclear both the nature of malignant neoplasms and the primary stimulus that initiates an inevitable chain ...

Over time, the identification of the carcinogenic properties of chemical agents has become only a matter of technology, and there has been a clear shift in research focus from routine testing for carcinogenicity to the study of the mechanism of oncogenic action. In this case, along with significant successes, considerable difficulties were revealed. Successes concerned the purely chemical side of the problem: the need for activation of the original carcinogens was established, metabolism, interactions were studied ...

How does the invasion of fragments of chemical carcinogens into DNA result in uncontrolled growth and transformation of cells? The theory of chemical carcinogenesis, in order to take a new and decisive step forward, needs some kind of scientific event, similar in significance to the discovery of reverse transcriptase in oncovirology. In the theory of chemical carcinogenesis, such an event has not yet occurred. However, you can expect…

The main success of oncovirology today should be considered the discovery of oncogenes - discrete material genetic elements in the DNA structure of cells responsible for the induction of malignant tumors in humans and animals. This line of research is the most promising in modern theoretical oncology. Oncogenes have been found in the genomic DNA of not only animals, but also humans, and the likelihood of their involvement in tumor induction…

Even I. M. Sechenov in 1860, in the theses of his doctoral dissertation, wrote that in the present state of the natural sciences, the only possible principle of pathology is molecular. Now one can only marvel at this providence. Today molecular oncology stands at the threshold of the mystery of cancer. It is she who owns the most outstanding successes in the field of theoretical oncology in recent years. These include the following…

If molecular biology in the most concise interpretation can be characterized as a science that expresses and explains complex general biological phenomena in terms of the properties and interactions of molecules, then molecular oncology, of course, is designed to reveal the molecular mechanisms of the process of carcinogenesis and the characteristics of tumors. This book attempts to summarize the progress of this young science. All the greatness of progress in the knowledge of tumors in our ...

The use of gene transfer and molecular cloning techniques has made it possible to establish some of the most important, central determinants of the cancer process. These determinants are oncogenes and their products are oncoproteins that act both on the structure and functions of cells and affect the regulatory mechanisms of biochemical reactions. Many of these functions of oncogenes and oncoproteins are still unknown, however, with the current level of knowledge, they ...

The oncoprotein p21cras, during cell transformation, apparently significantly affects the bioenergetics of the cell and the transmission of the regulatory signal from cell membrane into the core. It is also undoubted that the p2jcras oncoprotein in its multifunctional action in the process of malignancy of the target cell cooperates with the functions of other activated proto-oncogenes. For some steroid hormones, such as glucocorticoids, a mechanism has been established for transmitting their information from a specific ...

AT last years methods of molecular and genetic research were developed and put into practice malignant cells. These studies allow us to determine the degree of aggressiveness of the tumor and, as a result, the appointment of the most appropriate cancer treatment in Germany.

In some cases, it is worth limiting only surgical intervention and the disease will not return even without the use of chemotherapy and radiation. It is also possible to analyze certain cancer cell growth receptors, blocking which with special antibodies can prevent their further reproduction.

In addition, in modern oncology, it is possible to determine mutations (genetic damage) in the enzymes of tumor cells, which are responsible for whether a given tumor is amenable to certain chemotherapy or not.

We offer you to send us by mail a block with the pathology of your biopsy or operation even without coming to Israel or Germany. On the basis of the ‹‹Genomics›› laboratory, we carry out genetic and molecular analysis of the material, after which, based on the nature of the tumor, leading oncologists in Israel and Germany will provide you with specific recommendations in the treatment of cancer to achieve the most effective result with the least harm to the body.

‹‹OncotypeDX›› is not an experimental study. The results of these tests are based on observation of patients over 8 years. They are widely used in the largest cancer centers in the world and have saved hundreds of thousands of people from the use of ineffective chemotherapy.

What tests exist and who are they suitable for?

Oncotype DX for Breast (Breast) Cancer

1.a) Oncotype DX ® breast

‹‹Oncotype DX ® breast›› is a diagnostic test that is performed after surgical treatment of breast cancer. Suitable for menopausal women with invasive breast cancer, estrogen receptor positive (ER+) and HER 2 negative tumors with intact lymph nodes.

The ‹‹Oncotype DX breast›› test provides Additional information, with which doctors apply the decision on the course further treatment.

This is due to the fact that the results of the study determine the degree of aggressiveness of the tumor, the chance of recurrence and the need for chemotherapy.

The ‹‹Oncotype DX›› test presents necessary information in addition to standard tumor characterization measurements such as tumor size, tumor grade, and lymph node status, which are traditionally used by clinicians for evaluation. In the past, based on these parameters, a decision was made on the tactics of further treatment. With the advent of the ‹‹Oncotype DX breast›› test for 21 genes, physicians have an effective tool that indicates the degree of effectiveness of a chemotherapeutic or hormonal treatment.

To date, the results of the Oncotype test are the most important test in deciding whether to use chemotherapy in the treatment of breast cancer, it fundamentally changes the decision compared to what was used in the past without its use. Since the types of tumors are different for everyone, it sometimes happens that a small tumor with unaffected lymph nodes can be very aggressive. Therefore, intensive chemotherapy is necessary. On the other hand, in cases where this is not the case, with the ‹‹Oncotype›› test, you can save yourself from unnecessary chemotherapy and the side effects associated with it.

Below we present the stories of several patients who have benefited from the ‹‹Oncotype DX›› test.

Susan, aged 59, a routine mammogram revealed cancer.

After surgery to remove the tumor and biopsy of the lymph nodes, Susan underwent a series of examinations, including PET/CT, to assess the extent of the spread of the cancer. She was relieved when all those tests came back negative, but Susan wanted to make sure her illness wouldn't come back. After hearing about ‹‹Oncotype DX ®›› from a friend, Susan asked her doctor if the test was right for her. The initial tumor findings were suitable for the test, as her tumor was estrogen receptor positive and lymph node negative. Susan's doctor was very surprised when he saw the result of ‹‹Oncotype DX››, it was - 31, which indicates high risk cancer recurrence, and chemotherapy is necessary additional treatment in this case. Based on the result of the ‹‹Oncotype DX›› test, Susan's attending physician recommended several rounds of chemotherapy, which she started immediately to avoid possible relapse diseases. Before the test, Susan's doctor was sure that chemotherapy was not needed, but after learning about the high risk of a return of the disease, he changed his mind.

A commercial airline pilot with 27 years of experience, Diana, 50, discovered a small lump in her left breast during a self-examination.

A tissue biopsy confirmed her worst fears. Diana's cancer took the form of multiple small tumors scattered across her breasts. She was immediately operated on - the entire breast was removed. Although the tumors themselves were very small, Diana's doctor could not confidently rule out the need for chemotherapy based on standard measures such as tumor size and stage. Diana was worried about her future health and work safety. "Because I'm small, there has been concern that I'm less able to withstand the severe side effects of chemotherapy," Diana said. "In addition, the airline has been vigilant about the health of its pilots, and a cancer diagnosis could mean a permanent suspension from flying."

Seeking information, Diana's doctor turned to Oncotype DX for a genomic analysis of her illness. About a week later, Diana learned that her score was 13, suggesting that she had more low risk relapse (return of the disease). During the conversations with her doctor, she felt confident that she could avoid chemotherapy and her side effects without increasing the likelihood of recurrence of the disease, and she was able to continue her career and active image life. In addition, she was able to keep her long hair, which she grew from the age of 23. "Thirteen is mine lucky number currently," Diana said.

The test is suitable for menopausal women with invasive breast cancer, estrogen receptor positive (ER+) and HER-2 negative tumors, with normal lymph nodes. It is performed on a tissue sample of a removed tumor during surgery.

1.b) Immunohistochemical test of ER, PR, HER-2 receptors in tumor cells

Genetic analysis Fish-response to the antibody ‹‹Trastuzumab›› (Herceptin).

Immunohistochemical study: checking the tumor for special proteins - receptors located on the surface of tumor cells and being a target for drugs.

Analysis of estrogen, progesterone, HER-2 receptors allows us to establish their sensitivity to hormone therapy and to a specific antibody ( biological drug, not chemistry, a new generation of oncological drugs).

A tumor DNA test that tests genes in tumor cells for antibody susceptibility. Herceptin (Fish reaction) is suitable in 20-25% of breast cancer patients. This medicine significantly increases life expectancy in metastatic disease and prevents the return of the disease after surgery.

The above tests are suitable for both initially detected tumors at any stage, and for metastatic tumors.

1.c) CYP2D6 test

After surgery, many women are shown preventive treatment to prevent future recurrence. If there are estrogen receptors and progesterone receptors in the tumor tissues, then menopausal patients are often prescribed hormone therapy, Tamoxifen tablets for 5 years.

Recent studies have found a specific enzyme in liver cells that activates the drug ‹‹Tamoxifen›› in active substance‹‹Endoxifen››, which destroys cancer cells.

Therefore, the effectiveness of the drug is largely determined by the degree of activity of the liver enzyme CYP2D6, and the activity of the enzyme is determined by the genes of the patient.

This genetic test detects mutations in genes associated with the CYP2D6 enzyme, and allows you to accurately assess the degree of enzyme activity and the effectiveness of the drug Tamoxifen ››.

Determination of the CYP2D6 genetic code helps in choosing the right hormonal treatment and provides an opportunity to predict the effectiveness of the use of ‹‹Tamoxifen›› individually for each patient.

From medical literature it is known that 7-10% of the population of Europe and the USA have an ineffective enzyme, in these cases ‹‹Tamoxifen›› is an ineffective medicine.
It is very important to find those women for whom ‹‹Tamoxifen›› treatment is not suitable due to inefficient drug metabolism caused by low CYP2D6 enzyme activity. These patients are at increased risk of recurrence of breast cancer when taking ‹‹Tamoxifen››, and they need to take other hormonal drugs.

The test is intended for patients who are expected to be prescribed ‹‹Tamoxifen››, at an early or metastatic stage of the disease. The analysis is carried out using the patient's saliva.

2. Oncotype DX ® colon for colon cancer

2A. Oncotype DX®colon is a diagnostic test that is performed after the surgical removal of colon cancer. The ‹‹Oncotype DX colon›› helps men and women with colon cancer learn more about biological features tumors and determine the likelihood of recurrence. Combined with other pieces of information, the results of the ‹‹Oncotype DX colon›› trials can help patients and their physicians make personalized decisions about whether or not to use chemotherapy in complex treatment colon cancer.

One of the main problems in the treatment of patients with colon cancer is to determine the risk of recurrence of the disease after surgery and assess the need for postoperative chemotherapy in order to reduce the chance of recurrence.

Oncotype DX provides new way assessing the risk of recurrence in stage II colon cancer (without lymph node involvement) and increases the ability to make an informed decision individually for each patient.

You have recently been diagnosed with stage II colon cancer without lymph node involvement and have been surgical resection. Do you and your doctor have to make a decision about chemotherapy?

The ‹‹Oncotype DX›› test provides the necessary, additional information based on the genomic features of the tumor, which doctors use when making decisions about treatment tactics. It also indicates the likelihood of recurrence. The ‹‹Oncotype DX colon›› test provides information in addition to standard data such as tumor stage and lymph node status, which physicians and their patients traditionally use to assess whether the disease is likely to recur. In 15% of cases, the tumor of the colon is absolutely non-aggressive, and in this case, chemotherapy only brings harm to the body, because. the disease will never return.

Below are answers to the most frequently asked questions about the ‹‹Oncotype DX colon››

1. What is the ‹‹Oncotype DX colon›› test?

‹‹Oncotype DX colon››- tests colon cancer cells by looking at the activity of 12 human genes in order to assess the likelihood of the return of colon cancer in patients with early stage colon cancer with intact lymph nodes.

2. Who is the ‹‹Oncotype DX colon›› suitable for?

Men and women with newly diagnosed stage II colon cancer.

3. How does the ‹‹Oncotype DX colon›› test work?

The DNA that makes up the cell is extracted from tumor samples and then analyzed to determine the degree of activity of each of the 12 genes. The results of the analysis are calculated using a mathematical equation to convert the value into a numerical result.
This result corresponds to the probability of colon cancer recurrence within 3 years of initial diagnosis among individuals with early stage(second stage) colon cancer who underwent surgery to remove the primary tumor.

4. How long does testing take?

It usually takes 10 to 14 calendar days, since the arrival of pathology in the laboratory. The results of the study come in the form of a number on a scale from 0 to 100, and indicate the degree of likelihood of a relapse.

The ‹‹Oncotype DX colon›› is the doctor's advanced tool for assessing the severity of colon cancer and assisting in personalized treatment.

2B. Mutation testing in the K-RAS-Test is suitable for patients with metastatic colon and rectal cancer

One receptor that is characteristic of colon tumors is the epithelial growth factor receptor or epidermal growth receptor EGFR. These growth factors with a specific growth receptor trigger a chain of reactions that promote the development and division of the tumor cell. Changes, mutations (genetic failures of the code that determines the structure of the receptor), activation of EGFR receptors, can lead to constant uncontrolled cell division - these are necessary prerequisites for the appearance of malignant tumors. Determination of the EGFR receptor (a gene that can lead to cancerous transformation) is the target receptor for targeted treatment of tumors of the colon and rectum.

The drug - the antibody ‹‹Erbitux›› (Setuximab) blocks these receptors and thus prevents further division and growth of malignant cells.

What is K-RAS?

One of the "actors" involved in the chain of events. The action occurs after the activation of the EGFR family protein. The K-RAS receptor, this protein is a link in the chain of division signals in cells, which ends in the cell nucleus.

When there is a mutation in the K-RAS receptor, even if the EGFR receptor is blocked by the Erbitux›› antibody, it will still occur chain reaction cell division, bypassing the EGFR receptor link, in other words, the antibody will be absolutely ineffective.

On the other hand, if there is no mutation in K-RAS, then the biological drug ‹‹Erbitux›› gives a statistically significant improvement in the survival of patients with metastatic disease. In 55-60% of cases, no mutation is observed, that is, it is possible to treat with an antibody.

Complex treatment with ‹‹Erbitux›› in combination with chemotherapy allows to reduce metastases, and in the future, in some cases, they may surgical removal which can lead to full recovery.

If 10 years ago, patients with the fourth metastatic stage of colon disease lived an average of a year, now they live 3-5 years, and in 20-30% of cases a complete recovery is possible.

Thus, the test for the presence of a mutation in K-RAS helps to assess the degree of effectiveness of treatment. biological preparations in metastatic colon cancer.

The test is suitable for patients with metastatic colon and rectal cancer.

To conduct the test, you need a block with tissue from a biopsy tumor or a sample from a removed tumor.

3. Checking for EGFR mutations - non-small cell lung cancer

On tumor cells of non-small cell lung cancer, there are growth receptors responsible for the process of cell division.

Special enzymes that transmit signals for cell division are called tyrosine kinase.
Tyrosine-Kinase inhibitors are targeted drug therapies that block signals that promote tumor growth. These new drugs, small molecule tyrosine kinase and epidermal growth factor receptor (EGFR) inhibitors (Erlotinib (Erlotinib), Gefitinib (Gefetinib) were originally developed for use as second-line therapy after chemotherapy failure.

Under these conditions, Erlotinib showed an increase in survival rate, with outcome magnitudes similar to second-line chemotherapy, but without severe side effects. Since this is a targeted therapy, specific cancer cells are affected without harming normal cells, thus not harming the body.

Clinical studies have shown a correlation between the presence, activation of specific mutations in the T3 region of the EGFR receptor, and an increase in the activity of small molecule drugs - Erlotinib and Gefitinib. The presence of a mutation was found in 15-17% of patients, and instead of heavy chemotherapy with side effects, an antibody in tablets is suitable for them. The antibody can be given as the first line of treatment for metastatic disease. This drug can inhibit the growth of a tumor for years, as it blocks the tumor growth receptor.

The test is suitable for patients with non-small cell lung cancer with metastases, both before the start of any chemotherapy, and when the disease progresses during treatment. It is carried out on the biopsy block or on the material obtained during the operation.

4. New survey - Target Now (Target check)

Just as there is a difference between different people, it also exists between different malignant tumors, even if they are of the same origin, from the same organ.
So, for example, breast cancer may respond to hormone treatment in one woman, and another woman will not respond to them. Today, with the development of medicine, tests have been developed that help doctors choose treatment individually for each patient, thereby significantly increasing the effectiveness of treatment and reducing the risk of unwanted side effects.

What is Target Now?

This is a study conducted on the material of cancerous tissue removed during an operation or biopsy.

Research checks potential targets in tumor cells for various drugs.
In accordance with these goals (the presence or absence of certain receptors, mutations or their absence) allow the doctor to choose one or another drug that kills a specific tumor.

The test determines in cancer cells big number molecules that can be used as a site of action or target, chemicals and/or various biological antibodies. Molecular changes may indicate the expected good efficacy or ineffectiveness of a given treatment.

The results of this study were published in 2009 at the annual meeting of the American Association for Cancer Research. The test was conducted on 66 patients suffering from metastatic cancer. Based on the results of the Target Now test, patients were selected necessary treatment, after the standard treatment used for their disease proved to be ineffective.

The study found that molecular targets can be detected in 98% of cases.

In addition, adjusted treatment based on the results of the ‹‹Target Now›› test in one third of patients was found to prolong the time to disease progression by 30% compared to past treatment before the Target Test. Many patients have been extended life for many months and even years. It must be emphasized that we are talking about patients who were not helped by many drugs prescribed according to the scheme generally accepted for their disease.

From the results of Targeted Testing, it was found that their particular tumor is often treated with drugs that are usually not suitable for their type of cancer in the general group.

This study indicates that the Target Now test can detect drugs that are personally appropriate for a given tumor, which is difficult to determine in any other way today. A targeted test now allows for optimal adjustment of individual drugs before starting cancer treatment.

This study is suitable for patients with metastatic disease of any organ who have not responded to previous treatment.

To conduct the study, it is necessary to have tissue from a biopsy or after surgery.

5. Mamma Print - a test to determine the risk of breast cancer recurrence

MammaPrint is a diagnostic test to assess the likelihood of recurrence, which can predict the possible occurrence of recurrence of breast cancer within 10 years after treatment of the primary tumor.

MammaPrint is the only test of its kind that received FDA approval in February 2007.

The results of this test allow you to choose a technique after surgical treatment. If there is a high risk of recurrence, chemotherapy is indicated.

According to the FDA recommendations, this test is indicated for patients under 61 years of age, without affected lymph nodes, with a tumor size of less than 5 cm. MamaPrint is effective in hormone-dependent breast cancer and other types of malignant tumors.

This test is based on the analysis of 70 oncogenes associated with breast cancer. The analysis of these genes makes it possible to predict with great accuracy how a particular malignant tumor will behave in the future, this will allow the attending physician to select the necessary treatment with great accuracy.
The test is performed on tumor tissue taken during a biopsy or after surgical removal.

MamaPrint is the first highly individualized diagnostic test.
Today this method is very popular, for the sake of diagnostics with its use, many patients from the CIS countries come to Israel.
To take this test, you need to come to Israel for a few days, undergo a biopsy or surgical operation as the test requires fresh tissue samples. After that, you can go home or wait for the diagnostic results in Israel. It will take about 10 days to wait.

Treatment in Israel with the "Cancermed" center is the organization of high-quality medical care.

One of the most modern and high-tech methods for diagnosing cancer is genetic (molecular) tests. These studies make it possible not only to determine the hereditary predisposition to certain oncological diseases, but also to assess the feasibility of prescribing chemotherapy and determine the degree of cancer aggressiveness.

In the first medical center Tel Aviv conducts the most effective and proven genetic research of more than 900 existing on this moment. At the same time, a remote testing service is provided when the patient does not need to fly to Israel. It is enough to send a sample of the material by mail (after a puncture or operation), following some rules, and wait for the results of the study.

Oncotype DX

This molecular study is applied in breast cancer. Depending on the objectives of the study, the type of tumor and the individual characteristics of the patient, there are several types of Oncotype DX.

Oncotype DX Breast

The test is used to determine the degree of differentiation of breast cancer tumor cells (the probability of recurrence is determined accordingly). It is used after surgery to remove the tumor to determine the advisability of prescribing chemotherapy. The study is suitable for estrogen-positive tumors (ER+), invasive cancer breasts without metastasis to regional lymph nodes.

Standard signs for the choice of treatment tactics after surgery are:

Before the advent genetic tests, these three signs were the only source information, on the basis of which the tactics for the further appointment of chemotherapy was determined. However, the aggressiveness of cancer cells and, accordingly, the likelihood of a distant recurrence does not always correlate with the size of the tumor and the presence of metastases in the lymph nodes.

Today, in world medicine, the Oncotype DX genetic test is the gold standard and the leading criterion for choosing treatment tactics for breast cancer. It allows both to prevent the recurrence of the disease, and to avoid unnecessary prescription of chemotherapy and all the side effects associated with it.

Fish test for Herceptin receptors

It is an immunohistochemical study that detects specific receptors (HER-2, PR, ER) on cancer cells, which make it sensitive to targeted drugs. Such, in particular, is the drug Herceptin, belonging to the class of monoclonal antibodies. It has long been successfully used in the treatment of breast cancer in Israel and has shown nice results to prolong life and prevent recurrence, even in advanced stage and the presence of metastases.

In about 1 in 4 cases of breast cancer, the tumor is sensitive to Herceptin therapy and this can be determined by a molecular test for specific receptors. The advantage of biological treatment compared to standard methods(radio and chemotherapy) is the absence of harmful side effects.

Molecular test of the CYP2D6 gene

It is used exclusively in cases of hormone-dependent breast tumors. These cancer cells have receptors for the hormones estrogen and progesterone, which makes them sensitive to the effects of hormone therapy (especially in menopausal women).

Studies have shown that the hormone used replacement drugs converted in the liver to active active substance thanks to a special enzyme CYP2D6, encoded by the gene of the same name. On average, up to 10% of people have a mutation of this gene, due to which a full transformation of hormones is impossible.

A genetic test makes it possible to identify this mutation and thus determine whether effective treatment hormonal drugs and assess the risk of relapse. Tel Aviv First Medical Center this study carried out with material from the patient's saliva.

Oncotype DX Colon

A molecular study that is used in colon cancer to comprehensively weigh the risk of recurrence and the degree of tumor progression. The essence of the test is the analysis of 12 DNA genes by complex software cancer cell, which are responsible for the degree of differentiation, atypicality and gene aberrations. The result of the analysis is converted into a numeric form and has a value from 0 to 100.

The Oncotype DX Colon study is indicated for patients with stage 2 colon cancer after surgery to remove the primary tumor and in the absence of metastases in the regional lymph nodes. About 15% of patients with colon cancer have a non-aggressive form of the tumor that is not prone to recurrence. The test allows you to assess this risk and avoid unnecessary chemotherapy.

Duration genetic testing Oncotype DX Colon in Israel is about two weeks, and the material is taken directly from the primary tumor. The assessment is made on a 100-point scale, a comprehensive conclusion is made and the further tactics treatment.

K-RAS test

A specific genetic test that allows you to determine the sensitivity of colon cancer and to targeted therapy with Setuximab. The drug is a monoclonal antibody that selectively blocks EGFR receptors on tumor cells. The aggressiveness of colon and rectal cancer directly depends on the expression of specific epidermal growth factor receptors (EGFR).

K-RAS is a protein that is involved in a cascade of reactions that control cell division in the intestinal epithelium. Mutations in the gene encoding this protein make treatment with Setuximab ineffective. Approximately 60% of people do not have this mutation, so a drug can be given if the test is negative.

The K-RAS test is an extremely important diagnostic criterion in modern oncology. This is due to the fact that treatment with Setuximab prolongs life by 2-5 years or even leads to complete recovery of patients with advanced forms of neoplasms of the colon and rectum. Another 10 years ago metastatic cancer these departments of the gastrointestinal tract was considered incurable and patients received palliative therapy, with the introduction of biological therapy, patients got a chance for recovery.

EGFR mutation test

This genetic test is used for non-small cell lung cancer. There are two enzymes that control cell reproduction - tyrosine kinase and epidermal growth factor EGFR. Therefore, in modern methods Targeted tumor therapy uses two drugs that inhibit these enzymes, Erlotinib and Gefetinib.

According to statistics, from 15 to 20% of patients have an EGFR gene mutation, so they need to be prescribed targeted treatment in the form of monoclonal antibodies instead of second-line chemotherapy drugs. This is especially true for stages 3 and 4 of non-small cell lung cancer with the presence of metastases. Erlotinib and Gefetinib can inhibit the growth of cancer cells for years and cause a long-term remission in the patient. In addition, monoclonal antibodies do not have the negative side effects of chemotherapy (cytotoxic effect), since they do not affect healthy cells.

Comprehensive survey Target Now

Each atypical cancer cell has its own unique set of receptors and gene expression, just like each person has a unique fingerprint. The effectiveness of chemotherapy and treatment with biological targeted drugs depends on their presence or absence.

The current stage of development of treatment with monoclonal antibodies has acquired such a scope that for the most effective selection of the drug, it is necessary to carry out a lot molecular tests. The Target Now methodology allows you to combine them all into one study that accurately reflects genetic code atypical cell.

First official results tests were presented in 2009 at the American Research Association conference oncological diseases. According to them, more than 98% of patients with an advanced form of cancer (the presence of metastases) managed to get complete picture molecular targets and select the appropriate targeted therapy. Moreover, in 30-35% of patients, as a result of modified therapy according to the results of Target Now, there was a significant improvement in the quality of life and increased life expectancy.

The test is indicated for use in patients in whom previous treatment has not been effective, or with metastases of any localization. For the study, material from the tumor tissue is needed (biopsy, or after surgery).

Mamma Print

This genetic test is designed to determine the risk of recurrence after breast cancer. According to the recommendations of the American Food and Drug Administration (FDA), the test is indicated for patients with any form of breast cancer younger than 60 years old, without metastatic lesions of the lymph nodes, and provided that the tumor is less than 5 centimeters in size.

The essence of the study lies in the molecular analysis of the expression of 70 genes of a cancer cell, followed by an assessment of the aggressiveness of the tumor and the derivation of the final risk of recurrence using mathematical formula. The result allows you to choose the tactics of treatment and determine the feasibility of prescribing chemotherapy to patients.

The difference between Mamma Print and similar genetic tests is that the study is carried out on a sample of “fresh” tissue, so the patient must stay in Israel for a puncture or operation. You need to wait about a week for the result, but after the procedure you can go home and get an answer in writing.

Fill out an application for treatment

Crayfish mammary gland(BC) is one of the most common oncological diseases in Ukraine. According to the National Cancer Registry of Ukraine, the standardized incidence of breast cancer in 2009 is 60.5 cases per 100,000 female population. Although the incidence malignant neoplasms mammary glands is constantly increasing, mortality from them tends to decrease.

BC is a heterogeneous group of tumors that differ in morphology, clinical course and sensitivity to treatment. However, even histologically similar tumors have a different natural history, which is due to a certain limitation of the morphological classification of breast cancer. The study of gene expression by breast cancer cells and their correlation with phenotypic manifestations made it possible to identify a number of biological subtypes of breast cancer that determine the natural history, clinical, pathological and molecular properties of the tumor, and are also key factors that predetermine the prognosis of the course and the effectiveness of systemic drug therapy. Use in everyday clinical practice time-consuming and expensive methods genetic analysis impossible. The study of the correlation between gene expression and immunohistochemical markers in the tumor made it possible to identify a number of so-called molecular subtypes of breast cancer, the determination of which is possible in routine clinical practice. Based on an immunohistochemical study of the expression of estrogen and progesterone receptors (ER and PR) and epidermal growth factor 2 receptor (Her2/neu, ErbB2) by breast carcinoma cells, breast cancer can be classified into 4 molecular subtypes that differ from each other. according to the forecast of the current and the response to drug therapy. Molecular subtypes of breast cancer, which have a fundamental clinical significance, are given in table. one.

Table 1. Immunohistochemical phenotype of molecular subtypes of breast cancer

There are luminal, HER2+ and triple negative (TN) molecular subtypes of breast cancer. Luminal tumors include tumors expressing ER and PR receptors, and, depending on the expression of Her2/neu, they are classified into A (do not express Her2/neu) and B (express Her2/neu). HER2+ are called tumors with Her2/neu overexpression and lack of ER and PR. Tumors that are negative for the above 3 signs are referred to as TN (basal-like) BC. It has been established that luminal types are associated with a less aggressive course and a good prognosis compared with HER2+ and TN BC. TH subtype is associated with a high mutation rate BRCA1, aggressive course, lack of response to hormone therapy and trastuzumab, low overall and disease-free survival.

Correlation between immunohistochemical markers and tumor sensitivity to drug treatment well researched and underpinned clinical guidelines on adjuvant treatment of BC. However, the number of studies evaluating the relationship between molecular subtypes and clinical and biological characteristics of breast cancer is limited.

The purpose of this population study is to study the prevalence, clinical and morphological features, overall and relapse-free survival of patients with breast cancer, depending on the molecular portrait.

Materials and methods

Patient selection

The study included 350 patients with breast cancer aged 23 to 76 years ( average age- 53 ± 1.7 years), who were treated at the clinic of the Department of Oncology of the National medical university named after A.A. Bogomolets at the base surgical department Kyiv City Clinical Cancer Center from January 1, 2005 to December 31, 2006

All patients were recorded age at the time of diagnosis, menstrual function, determined the size, histological type and degree of differentiation of the tumor, as well as the presence of metastases in the regional lymph nodes (RLN).

Tumor size was assessed after measuring its maximum diameter and classified according to the International TNM classification (5th edition, 1997) as T1 (<2 см), Т2 (2–5 см), Т3 (≥5 см). Отсутствие менструаций у больных в течение 1 года до момента установления диагноза расценивалось как менопауза. Гистологический тип и степень дифференциации опухоли определяли в соответствии с национальными стандартами диагностики и лечения злокачественных новообразований, основанных на рекомендациях ведущих международных организаций. Для оценки метастатического поражения РЛУ из послеоперационного материала макроскопически отбирали 10 подозреваемых на наличие метастазов лимфатических узлов, из которых готовили гистологические препараты для микроскопического изучения.

Molecular subtypes of BC were determined based on the results of immunohistochemical studies of the expression of ER, PR, and Her2/neu. All tumors were divided into 4 subtypes: luminal A (Luminal A) - ER+ and/or PR+, Her2/neu-, luminal B (Luminal B) - ER+ and/or PR+, Her2/neu+, HER2+ (ER- and PR-, Her2/neu+), TH (Triple negative) - ER- and PR-, Her2/neu-.

All patients received adjuvant systemic and radiation therapy in accordance with national standards for the treatment of breast cancer. However, with Her2/neu overexpression, none of the patients included in this study received trastuzumab adjuvantly.

Immunohistochemical study

Sections of 4–5 microns thick were prepared from paraffin blocks and placed on slides pretreated with poly-L-lysine. Then the material was examined according to the generally accepted standard method using the following antibodies: ER - clone 1D5, PgR - clone 636, Her2/neu - clone CB11.

Interpretation of the results of the immunohistochemical reaction was carried out using a qualitative assessment of the nuclear reaction: negative "-", weakly positive "+", moderately positive "++", pronounced positive "+++" - and a quantitative system for evaluating the reaction in percent of stained tumor cells.

When determining the expression of Her2/neu, the severity of the color of the cytoplasmic membrane was noted: the reaction "-", "+" - the absence of overexpression, the reaction "+++" - the overexpression of Her2/neu. The presence of Her2/neu overexpression in cases of “++” reaction was assessed using the hybridization method in situ using a fluorescent label FISH (fluorescence in situ hybridization - fluorescent in situ hybridization). The studies were carried out in the pathohistological laboratory of the Kyiv City Clinical Cancer Center (head of the laboratory - Doctor of Medical Sciences L.M. Zakhartseva).

Statistical analysis

Statistical significance of differences between the clinical and biological characteristics of the molecular types of BC was assessed using a one-way analysis of variance (ANOVA). Differences were considered statistically significant at the significance level (p)<0,05.

Overall and disease-free survival was determined using the Kaplan-Meier method.

All statistical calculations were performed using the MS Excel program.

results

As a result of the study, all patients, based on the data of immunohistochemical studies of the expression of ER, PR and Her2/neu, were divided into 4 groups: luminal A - 152 (57.5%) patients, TN - 49 (26.5%), luminal B - 28 (9%) and HER2+ - 15 (7%) women.

Clinical and biological characteristics of various molecular types of breast cancer are presented in Table. 2.

Table 2. Clinical and biological characteristics of molecular subtypes of breast cancer

Notes: *lobular ductal carcinoma; **mucous, medullary, papillary carcinoma.

There were no statistically significant differences in the stage of the disease between the study groups, which indicates a homogeneous distribution of patients in groups according to this criterion.

The frequency of detection of various molecular subtypes of breast cancer statistically significantly depends on the following clinical and morphological characteristics: age and menstrual function at the time of diagnosis, histological type and degree of tumor differentiation. In patients aged 40–49 years, HER2+ and TN subtypes of breast cancer are diagnosed significantly more often (34.5 and 34% of cases, respectively). Almost half of the patients (48%) with TN of the molecular type were diagnosed in premenopause. In patients who were in menopause at the time of diagnosis, luminal A (63%) and luminal B (68%) types of BC are more common than others.

Also, statistically significant differences between immunohistochemical subtypes were observed for different histological types and degree of tumor differentiation. Lobular carcinomas were diagnosed more frequently in luminal A (19%) and TN (16%) types. Ductal breast cancer was recorded in 84 and 92% of cases of HER2+ and luminal B molecular subtypes, respectively. Lobular ductal, mucosal, medullary, and papillary carcinomas are equally common in luminal and TN types of breast cancer, but this study did not record a single case of the above histological variants in HER2+ type. In the studied groups, highly differentiated (G1) tumors are determined with the same frequency. Moderately differentiated (G2) breast carcinomas are typical for luminal A (82%) and B (86%), as well as HER2+ (80%) types. Poorly differentiated (G3) tumors were found in 28% of patients from the TN BC group.

Statistically significant interdependence between the immunohistochemical phenotype of breast cancer and the size of the primary tumor, as well as the status of RDR, has not been established, which, along with the stage of the disease, indicates a uniform distribution of patients in the study groups according to these indicators.

The results of the analysis of 5-year overall and relapse-free survival of patients with different molecular types of breast cancer are shown in Fig. 1 and 2, as well as in the table. 3 and 4, respectively.

Rice. one.

Rice. 2.

Table 3 Overall survival of patients depending on the molecular type of breast cancer

Table 4 Relapse-free survival of patients depending on the molecular type of breast cancer

Overall survival is highest in patients with luminal A (74%) type of breast cancer, and the lowest in patients with HER2+ and luminal B (58 and 57%, respectively).

5-year disease-free survival is worse in patients with luminal B and TN breast cancer (42 and 45%, respectively) compared with patients with luminal A immunohistochemical subtype.

Discussion

The results of this study confirm the variability of breast cancer, which consists in the presence of different molecular types of this nosological form. The division of breast cancer into biological subtypes, which have their own natural history, is increasingly used in everyday clinical practice, as it allows you to determine the prognosis of the course of the disease and is a key factor in choosing the tactics of systemic drug therapy. However, classification into molecular types does not replace but rather complements important traditional prognostic criteria, such as age and menstrual function at diagnosis, tumor size and differentiation, presence of RLN metastases, and identification of comorbidities.

Determination of molecular types of breast cancer based on immunohistochemical assessment of the expression of ER, PR and Her2/neu is inexpensive and quite informative, but at the same time a simplified diagnostic method. Due to the introduction of new markers, molecular classification is undergoing changes, which makes it possible to increase its predictive reliability. Thus, for example, at high mitotic activity of cells (Ki-67 >14%), tumors with a luminal A phenotype, according to the recommendations of the St. Gallen Congress on the treatment of breast cancer (2011), are assigned to the luminal B Her2/neu-negative molecular subtype. The need to isolate the luminal B Her2/neu-negative type of breast cancer is dictated by the natural history of these tumors, which is more similar to the natural history of luminal B than luminal A tumors. Therefore, patients with ER+ and/or PR+, Her2/neu- BC with high mitotic activity of the tumor, which determines a poor prognosis of the course of the disease, are shown to undergo adjuvant polychemotherapy before antihormonal therapy.

The results obtained in this population study indicate that the frequency of detection of different molecular types of breast cancer, determined on the basis of immunohistochemical assessment of the expression of ER, PR and Her2/neu, is not the same. The most common molecular subtype of BC is luminal A (57.5%), followed by TN (26.5%), followed by luminal B (9%) and HER2+ (7%) types.

Luminal A immunohistochemical type of breast cancer in most cases is diagnosed in patients after 50 years of age who are in menopause. This variant of breast cancer is more often than others characterized by a lobular histological type and a moderate degree of tumor differentiation. The 5-year overall and relapse-free survival of patients with this molecular type of breast cancer is the highest and amounts to 74 and 62%, respectively.

TN BC is more often detected in patients aged 40 to 60 years, regardless of the state of menstrual function, it is characterized by a lobular histological type in 16% of cases, and in 28% these tumors are poorly differentiated. Compared with luminal A type, in patients with TN BC, the 5-year overall and recurrence-free survival is lower and amounts to 60 and 45%, respectively.

Luminal B molecular type, like luminal A, is more often diagnosed in postmenopausal women over 50 years of age. More than 80% of cases are moderately differentiated ductal carcinoma. Patients with luminal B BC have the lowest 5-year overall and recurrence-free survival and are 58 and 42%, respectively.

HER2+ type, like TH, occurs more often in patients aged 40 to 60 years, regardless of the status of menstrual function, and is almost always a moderately differentiated carcinoma. The 5-year overall and disease-free survival rates are the same at 57%.

Thus, the most favorable molecular subtype of breast cancer in terms of its prognosis is luminal A. The unfavorable clinical course of luminal B and HER2+ types may be due to the lack of trastuzumab therapy.

List of used literature

1. Bulletin of the National Cancer Registry No. 12. Cancer in Ukraine, 2009–2010, Kyiv: 2011.

2. Perou C.M., Sorlie T., Eisen M.B. et al. (2000) Molecular portraits of human breast tumors. Nature, 406(6797): 747–752.

3. Sorlie T., Perou C.M., Tibshirani R. et al. (2001) Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc. Natl. Acad. sci. USA, 19(98): 10869–10874.

4. Sorlie T., Tibshirani R., Parker J. et al. (2003) Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc. Natl. Acad. sci. USA, 14(100): 8418–8423.

5. Sotiriou C., Neo S.Y., McShane L.M. et al. (2003)Breast cancer classification and prognosis based on gene expression profiles from a population-based study. Proc. Natl. Acad. sci. USA, 18(100): 10393–10398.

6. Carey L.A., Perou C.M., Livasy C.A. et al. (2006) Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study. JAMA, 21(295): 2492–2502.

7. Foulkes W.D., Stefansson I.M., Chappuis P.O. et al. (2003) Germline BRCA1 mutations and a basal epithelial phenotype in breast cancer. J. Natl. Cancer Inst., 19 (95): 1482–1485.

8. Liu H., Fan Q., Zhang Z. et al. (2008) Basal-HER2 phenotype shows poorer survival than basal-like phenotype in hormone receptor-negative invasive breast cancers. Hum. Pathol., 2 (39): 167–174.

9. Goldhirsch A., Wood W.C., Coates A.S. et al. (2011) Strategies for subtypes-dealing with the diversity of breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011. Ann. Oncol., 8(22): 1736-1747.

Molecular types of breast cancer, determined on the basis of immunohistochemical markers: clinical and biological features and prognosis

I.B. Shchepotin¹, O.S. Zotov¹, R.V. Lubota¹, M.F. Anikusko², I.I. Lubota²

¹National Medical University named after O.O. Bogomoltsya, Kiev

2 Kyiv City Clinical Oncology Center

Summary. Cancer of the thoracic cavity is a heterogeneous group of puffs, which are considered by their etiology, morphological picture, clinical overshoot and sensitivity to the treatment. The method of this population study led to the development of breadth, clinical and morphological features, general and disease-free survival of ailments for breast cancer in a fallow type of molecular type. 350 patients with breast cancer were treated at age 23 to 76 (middle age - 53±1.7 years), and they were treated at the clinic of the Department of Oncology of the National Medical University named after O.O. Prayers on the basis of the surgical department of the Kiev Moscow Clinical Cancer Center in 2005–2006. Statistically significant differences between the molecular type of breast cancer and clinical and morphological features were revealed, as well as: age and status of menstrual function at the time of diagnosis, histological type and degree of differentiation of swelling, as well as overall and disease-free survival.

Keywords: thoracic cancer, molecular types, prognosis of overcome, clinical and morphological features.

Molecular types of breast cancer, established on the basis of immunohistochemical markers: clinical and biological characteristics and prognosis

I.B. Schepotin¹, A.S. Zotov¹, R.V. Liubota¹, N.F. Anikusko², I.I. Liubota²

¹A.A. Bogomolets National Medical University, Kyiv

2 Kyiv municipal clinical oncological center

summary. Breast cancer (BC) is a heterogeneous group of tumors that has a different etiology, morphological pattern, clinical course and sensitivity to the treatment. The aim of this study was to investigate population prevalence, clinical and morphological features, general and disease-free survival of BC patients depending on the molecular type. The study involved 350 patients with BC aged 23 to 76 years (mean age 53±1.7 years.) They were treated in the clinic of the Department of Oncology A.A. Bogomolets National Medical University, based on the surgical department of the Kyiv City Clinical Cancer Center in 2005–2006 years. A statistically significant difference between type BC molecular and morphological features, namely age and status of menstrual function at the time of diagnosis, histological type and degree of tumor differentiation, as well as general and disease-free survival of patients.

key words: breast cancer, molecular types, prognosis, clinical and morphological features.

Republican Scientific and Practical Center of Oncology and Medical Radiology named after A.I. N. N. Alexandrova is currently carrying out 56 scientific projects, 23 of which are related to molecular genetic research. They are carried out at the Republican Molecular Genetic Laboratory of Carcinogenesis (oncology department of genetics, cellular and biochip technologies, virology, immunology and proteonics).

Traditional diagnostic tools are exhausting their potential, - says the Deputy Director for Research of the Republican Scientific and Practical Center, Corresponding Member of the National Academy of Sciences of Belarus, Doctor of Medicine. sciences, professor Sergey Krasny. - It's time to use such a reserve as molecular genetic research. They make it possible to test tumors with high accuracy to determine chemosensitivity, to establish the hereditary nature of the disease by the genetic portrait of the patient, and to purposefully act proactively by prescribing targeted treatment.

In 2016, about 10,000 patients passed through the Republican Scientific and Practical Center, approximately 7,000 of them underwent molecular biological studies; large-scale tumor profiling for individualization of therapy was carried out on about a hundred people. On the basis of molecular biological markers, the diagnosis of tumors of the central nervous system, soft tissues and bones, lymphoma was carried out, studies were conducted to assess the hereditary risks of developing malignant neoplasms, monitoring the concentration of drugs in body fluids for individual dose adjustment of the drug, cell therapy technologies were developed and implemented.

To implement the achievements of molecular biology in the domestic clinic, the first international certificates have already been received, modern equipment has been purchased for performing fluorescent in situ hybridization, molecular sequencing, polymerase chain reaction (PCR), immunohistochemistry, chromato-mass spectrometry, flow cytometry, enzyme immunoassay.

Biologist Victoria Mayorova prepares samples for PCR reaction.

New developments

A method for assessing the prognosis of the clinical course of bladder cancer through a comprehensive analysis of the clinical and morphological parameters of the tumor and the molecular genetic status of the FGFR3 gene.

Based on this analysis, a model of molecular pathways for the pathogenesis of bladder cancer was created. Depending on the presence of a certain mutation, pathology can develop in two ways: the so-called superficial cancer, characterized by low malignancy and a favorable prognosis (mutations in the FGFR3 and HRAS genes); a more aggressive muscle-invasive cancer that metastasizes early and is characterized by a poor prognosis (mutations in the TP53 and RUNX3 genes).

Using this method, a group of patients with a very high risk of disease progression, who had mutations in the TP53 and RUNX3 genes, was identified. This is important for predicting the course of the disease and determining the degree of aggressiveness of treatment. Knowing that the patient's tumor will develop as a superficial one, after treatment, the bladder will be mainly controlled.

If the progression of the disease is expected, then in relation to metastasis, the state of other internal organs will be monitored. In addition, patients may be identified who must immediately undergo a radical removal of the bladder, otherwise metastases will develop.

Non-invasive complex method of molecular genetic and radiation diagnostics of prostate cancer.

Such testing should be done when a patient with a high level of prostate-specific antigen (PSA) in the blood has an initial biopsy that is negative. Usually, another biopsy is performed six months later, followed by another (and so on 10-15 times), but this is an aggressive study, so a solution was required that would allow limiting ourselves to only one such intervention. Scientists have found a way. By detecting the expression of the PCA3 oncogene and the chimeric TMPRSS2-ERG gene in urine, it is possible to isolate patients who really need to undergo a biopsy (the rest can be delayed).

Development and implementation of a method for transplantation of tissue-engineered respiratory tracts with their lesions of tumor or cicatricial etiology.

We are talking about the category of patients who die within 2-5 months. A method was proposed for decellularization of the cadaveric trachea, in fact, with the preparation of a matrix, then populating it with chondrocytes and after that with epithelial cells. In addition, the technology provides for tracheal revascularization with subsequent transplantation to patients. All this is done in order to replace the defect of the trachea after removal of the tumor or scar. Currently, 3 surgeries have been performed. All patients have been living for more than six months - this is considered an encouraging result.

Laboratory diagnostics doctor Irina Vladimirovna Stukalova and Natalia Zakharovna Pishchik, a senior laboratory assistant, are preparing the analyzer for the isolation of human papillomavirus DNA.

Together with the Institute of Genetics and Cytology of the National Academy of Sciences of Belarus, the topic “Proteomic and molecular genetic studies of tumor stem cells (SSCs) of colorectal cancer for the development of new methods of targeted cell therapy” is planned (program of the Union State “Stem Cell - 2”).

Using a 5-fluorouracil-resistant colorectal cancer cell line model, it is planned to study the role of COCs in the mechanisms of tumor progression and to select possible molecular targets for direct action on COCs by vaccine-based cell therapy methods using dendritic cells and/or dendritic cells and lymphokine-activated killers. . This will be a new stage in the immunotherapy of malignant tumors.

Biologist Igor Severin in the cryobank of tumor cell lines.

Another project is “Development of technology for detecting the risk of cancer based on molecular genetic and epigenetic markers” (Union State program “DNA identification”). It is planned to develop an innovative DNA technology to identify molecular genetic and epigenetic markers of the risk of recurrence or progression of the disease in patients with colorectal cancer. According to experts, the new technology will allow timely preventive treatment and prevent the appearance of metastases.

A promising area of ​​research is the study of epigenetic mechanisms of regulation, i.e., processes that do not affect the structure of genes, but change their level of activity. One of them is RNA interference - a mechanism for suppressing gene expression at the stage of translation, when RNA is synthesized, but does not manifest itself in a protein. And if a high level of expression of some microRNA is detected, it can be assumed that there is a problem in this organ.

The miRNA gene family makes up slightly more than 1% of the entire human genome, but regulates the expression of almost a third of all genes. A number of ongoing scientific projects are devoted to the study of miRNAs in various tumors. The department is developing a non-invasive method for diagnosing testicular germ cell tumors, based on determining the expression of a microRNA panel in the blood. The same family of molecules, in addition to diagnosing diseases, is used to predict the course of oncological diseases and to select individual drug therapy.

The objective of the study is to determine the markers of poor prognosis (you can select a group of such patients and select additional treatment). It is also important to determine the miRNA spectrum. It will indicate sensitivity to certain chemotherapy regimens (we are talking about breast cancer, for which a panel of markers was found).

By studying the molecular characteristics during treatment, it is possible to adjust the treatment regimen when additional mutations appear. The method is called a “liquid” biopsy: a blood test can monitor genetic changes and suggest the progression of the disease much earlier.

Drugs for therapy are expensive and highly toxic, so it is important to determine drug resistance at an early stage and find a replacement.

Molecular profiling involves the determination of genetic disorders characteristic of each specific tumor, since it is known that the same nosological forms differ in molecular characteristics. Knowing the molecular portrait of a tumor is also necessary for predicting the course of the oncological process and individualizing treatment. A personalized approach to prescribing cytotoxic drugs and targeted therapy in cancer patients, taking into account molecular biomarkers of sensitivity and toxicity, provides the most accurate selection of drugs.

Within the framework of molecular profiling of tumors, based on a large-scale analysis of data from world publications, multiplatform panels of biomarkers for breast cancer, ovarian cancer, colorectal cancer, non-small cell lung cancer, and melanoma were developed, designed to select systemic antitumor therapy.

Chemist Olga Konstantin Kolos launches the synthesis of oligonucleotides.

Is it necessary to expand the geography of research?

Anna Portyanko,

head of the Republican

molecular genetic

laboratory of carcinogenesis,

doctor med. Sciences:

At the present stage, from the group of glioblastomas, variants have been identified that are characterized by a different prognosis. From a morphological point of view, it is easy to confuse glioblastoma and anaplastic oligodendroglioma: when stained with hematoxylin-eosin, they look almost the same. But thanks to genetic tests, we find differences. Moreover, it is routinely performed in our pathology department.

In a similar way, lymphomas also “multiplied”. For example, several lymphomas have been isolated from Hodgkin's lymphoma through molecular genetic testing. Previously, based on hematoxylin-eosin histology, they were classified as Hodgkin's lymphoma, and when molecular genetic analysis for the T-cell receptor appeared, it turned out that this was follicular T-cell lymphoma.

How does this affect treatment? First of all, it is possible to give a more accurate forecast. If a person has glioblastoma, then the median survival is 1 year, and if we are talking about anaplastic oligodendroglioma, then 10 years.

We develop contacts with foreign experts from the best European scientific centers. Together with colleagues from Germany, we are trying to develop important areas of proteomics - the analysis of not just one protein, but the proteome as a whole. The whole cycle has been created, starting from a cytological preparation, there is a laser microdissection system based on a microscope, which allows you to isolate tumor cells from a large tumor, then do mass spectrometry and determine the spectrum of all proteins in this tumor.

Is it necessary to expand the geography of research? I think it is enough for the country to have one such center - the Republican Molecular Genetic Laboratory of Carcinogenesis, where you can quickly perform all the necessary molecular biological studies (including with histological material obtained from the regions).

We have the opportunity to carry out not only histological diagnostics, but also preliminary diagnostics using a flow cytometer. Literally within an hour after a person's lymph nodes have been removed, we can preliminarily tell if there is a lymphoma (and if so, which one). This is a great help for clinicians.

Biologist Anastasia Pashkevich loads samples into a genetic analyzer.

What was Angelina Jolie afraid of?

We study genetic damage that occurs during the development of a tumor, - says Elena Suboch, head of the oncological department of genetics of the Republican Molecular Genetic Laboratory of Carcinogenesis. - The current direction is the assessment of hereditary risks of developing oncological diseases. Hereditary forms of tumors account for 1–2% of all oncopathologies, and here special treatment and surgical regimens should be applied. An important goal of identifying familial tumor syndromes is to identify still healthy relatives of the patient who have pathogenic mutations. As a result, it is possible to develop a set of measures aimed at preventing an unfavorable outcome of oncopathology.

An example is heard: American actress Angelina Jolie, who has a mutation in the BRCA1 gene that increases the risk of developing breast cancer, went for a radical operation to prevent the occurrence of a malignant tumor.

Scientists of the Republican Molecular Genetic Laboratory of Carcinogenesis are working on this pathology.

Under a grant from the Belarusian Republican Foundation for Basic Research, in 2015–2017, the work “The system of allelic discrimination of the mutational status of the BRCA1 and BRCA2 genes in malignant neoplasms of the human breast” was completed. A population study was conducted, and it turned out that the frequency of mutations in the BRCA1 and BRCA2 genes is approximately 2.5% among women (the frequency spectrum of mutations differs from that observed in residents of neighboring countries).

Each population has its own spectrum of genetic disorders. Knowing the characteristic mutations, you can first test them, and then look for other options. The result of the scientific project was the development of a system for allelic discrimination of the mutational status of the BRCA1/BRCA2 genes using real-time polymerase chain reaction. 5 main mutations that are found in Belarusian women have been identified.

Specialists of the Oncology Department of Genetics are also testing a large panel of markers to assess the risk of developing ovarian, endometrial, thyroid, kidney, colorectal cancer, melanoma, and polyposis syndromes.

Today, there are new international classifications of brain tumors and lymphomas that require mandatory molecular genetic studies. Therefore, in the departments of genetics and cellular technologies, an algorithm for diagnosing such diseases using biomarkers is being developed.