Arseny Basov, Deputy Chief Physician for Medical Affairs of the Consultative and Diagnostic Center of the N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation:
An international team of scientists found that the incidence of cancer in young people (under 50 years old) increased by 79% between 1990 and 2019. In addition, the incidence of cancer deaths in this age group increased by almost a third (27%). What could be the reason for this trend towards "rejuvenation" of cancer?
- "Rejuvenation" of cancer is largely associated with the development of diagnostics and active preventive measures - including the early detection of tumors during the medical examination of patients, but nevertheless there is also a true increase. Oncological diseases are now detected in patients at earlier stages than before, and it is also more accurately diagnosed.
For example, in Russia, the percentage of malignant tumors in the early stages detected in 2021 was almost 58%. At the same time, it is obvious that the sooner cancer is detected, the higher the chances of successful treatment of the patient and his return to normal life.
The active promotion of a healthy lifestyle, which is being carried out today in the media, as well as the dissemination of information about the importance of early prevention and screening of cancer, plays a role. This makes it possible to detect cancer more often - so it seems that the number of cases of cancer has increased.
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- What factors most often provoke the development of cancer? For example, how large is the share of viral origin, what role does nutrition and lifestyle play?
- There is a large group of common risk factors for cancer: old age, smoking, obesity, alcohol, HPV (human papillomaviruses), exposure to ultraviolet radiation, etc. They do not always lead to cancer, but in some cases they can provoke its appearance. At the same time, the impact of many negative factors can be avoided - for example, do not sunbathe in the sun, use sunscreen, get rid of tobacco addiction, etc. This, in turn, will reduce the risk of cancer.
In some cases, heredity plays a role - for example, if we are talking about breast cancer, then the family history of this disease is very important.
- How often do benign tumors degenerate into malignant ones?
- There is such a risk, but not all neoplasms. For example, degeneration is characteristic of some types of benign intestinal tumors. At the same time, lipomas (a benign neoplasm consisting of fat cells. —RT), lower risk of malignancy. Therefore, it is necessary to determine the risks in each case individually.
- What rules do each person need to follow in general in order to either prevent the occurrence of oncology, or at least detect it at an early stage? What preventive examinations and tests do I need to undergo?
- If we are talking about the detection of cancer in men, then starting from the age of 40-45 years, you need to regularly take a blood test for PSA (a protein that is produced by prostate cells and serves as an indicator of its condition. - RT).
As for women, you need to be regularly examined by a gynecologist, once a year to do an ultrasound of the mammary glands, and after 40 years - a mammogram. Both men and women who have reached the age of 45 need to perform a fecal occult blood test and a colonoscopy. It is important for smokers to have regular chest x-rays.
- Mammography procedure
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It is very important to undergo all routine examinations in a timely manner, even if nothing hurts or bothers. This is the only way we can detect cancer in its early stages. If you go to the doctors only when severe symptoms have already appeared, then, most likely, you will have to fight cancer in the later stages. Unfortunately, cancer practically does not manifest itself at a greater extent of its development in the body.
—How far has medicine progressed in the field of cancer treatment?Are long-known methods being improved: surgery, chemotherapy?
- The methods used today can be divided into three main areas: surgery, drug and radiation therapy. Each direction is intensively developing, and in some cases complex treatment is used - when, for example, radiation therapy and chemotherapy are added to surgery. New methods of surgical treatment, minimally invasive operations are being introduced into practice, allowing for intervention with minimal traumatic effect.
Drug therapy is becoming more selective - drugs affect malignant cells, but do not have the same high toxicity to normal cells. This, for example, is targeted drug therapy, where drugs have a targeted effect on tumor cells.
Radiation therapy is also being improved - new equipment is appearing, which makes it possible to increase the effectiveness of treatment due to more accurate irradiation of the affected tissues without touching healthy ones.
As molecular genetics advances, scientists are learning more about the molecular causes of cancer. Knowledge of these mechanisms makes it possible to improve both the diagnosis and therapy of cancer, and changes the nature of approaches to the search for new drugs.
- Radiotherapy
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Anna Stroganov, Head of the Laboratory of Molecular Genetic Diagnostics of the N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation:
- How does the formation of cancer cells and tumors occur - do we understand correctly that this is always the result of a genetic failure, a DNA mutation? If this is the result of random mutations, then why is cancer often hereditary? How is this predisposition expressed - is the mutation itself inherited or a predisposition to certain diseases that already provoke cancer?
- There are several theories of carcinogenesis, today the preference is given to the polyetiological theory, which takes into account internal factors, including genetic changes, as well as external factors - the reaction of tissues to damage. For example, in melanoma, both external influences play a role - inflammation caused by exposure to ultraviolet radiation, and internal - that is, mutations in oncogenes, which already lead to unlimited cell division and loss of differentiation - that is, its "specialization" in the composition of the body.
Hereditary forms of tumors account for only 5-10% of all cases of oncology. For example, it is known that hereditary breast and ovarian cancer in women is most often caused by mutations in the BRCA1 and BRCA2 genes. It has been proven that hereditary forms of pancreatic and prostate cancer are also associated with mutations in these genes. These genes have a very high penetrance (frequency of manifestations. - RT), which increases the likelihood of tumors of various localizations in their carriers. At the same time, it should be noted that it still does not reach 100%. If such a mutation is detected, surgical prophylaxis may be prescribed, this is also in the Russian clinical guidelines. The only thing is that in Russia such an operation can be recommended after the initial occurrence of a tumor in one mammary gland, for example. Whereas in other countries they can remove a potentially vulnerable organ even before the onset of oncology. As it was, apparently, in the case of actress Angelina Jolie, who had a mastectomy due to heredity, this was written a lot in the media.
- Angelina Jolie
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- And with the exception of these inherited cancers, does oncology mainly arise as a result of spontaneous mutations?
- The spontaneous occurrence of tumors is often the result of the activation of oncogenes, when the gene responsible for cell cycle control and cell "specialization" is mutated. I will add that the cause is not always a genetic mutation, there may be other factors that disrupt the work of these genes - for example, epigenetic, when a methyl group is attached to a given section of DNA - this changes the work of the gene.
Plus, disorders in the genes of the repair system can lead to oncology. In the process of cell growth and division, there are control moments at which there is a high risk of genetic disorders that can lead to the development of a tumor. Repair systems monitor and immediately correct such errors, returning the cell to its normal state. Therefore, disturbances in the repair system can also lead to oncology.
The third reason is the inactivation of suppressor genes, the proteins of which are also involved in tracking disorders in cell division. They do not "repair" damaged cells, but send them to apoptosis - that is, they program cell death.
- One of these genes - the TP53 gene, encoding the p53 protein, is responsible for detecting cell mutations and destroying mutated cells - it is even called the "guardian of the genome". How often does a malfunction of this gene cause the disease?
- Yes, it has been observed that in many malignant tumors this protein is inactivated. Each gene is represented by two copies—there are two alleles of each gene. Heterozygosity is lost in the tumor, that is, one of the alleles of the suppressor gene is deleted (destroyed), and the second allele is damaged. As a result, tracking DNA damage in this cell stops.
There is also a rare hereditary syndrome that is associated with a mutation in the TP53 gene called Li-Fraumeni syndrome (LFS), which increases the risk of developing certain tumors.
- Telomeres at the ends of chromosomes
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- The relationship between cancer and aging - it is known that in cancer cells, unlike normal cells, telomeres do not shorten when dividing. Therefore, some cancer cells are called immortal. Now in the world attempts are being made to find a universal method of treating cancer through the destruction of telomerase in cancer cells. In your opinion, how promising is this direction? And are there already the first clinically significant results?
Telomeres are structures at the ends of chromosomes that are involved in cell replication (division) and are responsible for their genetic stability. As the cell divides, the length of telomeres decreases, for each cell a limited number of divisions is determined, after the exhaustion of which it should normally die. The telomerase enzyme lengthens telomeres, and if they are not shortened, then the cell will not be able to go into apoptosis.
This leads to genetic instability, because errors accumulate in the DNA of such cells. High telomerase activity is indeed observed in tumor cells. Studies aimed at suppressing telomerase activity are underway, but so far on cell lines or animals. The first clinical trials of such techniques in humans are still very far away.
- Today, in cosmetology, for example, methods of stem cell rejuvenation are offered, in general, the topic of the therapeutic properties of stem cells is quite popular. Is there a risk that the introduction of stem cells into the body will provoke oncology?
- A stem cell isan undifferentiated cell, only ready to develop into cells of some tissue, thereby similar to the cells of malignant tumors, in particular in terms of the rate of division and the absence of differentiation. Methods of using stem cells take place in practice in order to rejuvenate and slow down aging, but we cannot accurately predict exactly how a stem cell introduced into the body will behave. So the use of stem cells is justified only if it is a medical necessity, when the benefits to the patient outweigh the risks.
- DNA image
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— Are there any methods of gene therapy for cancer today?
- So far, such methods have not been used, although experiments are actively conducted, including in Russia. On the basis of adenovirus, scientists create gene constructs that should be embedded in a tumor cell and block its uncontrolled division, send it to apoptosis. Or even to make a reverse differentiation - that is, to return its signs to the tissue from which it originated. But so far, such work is at the stage of laboratory experiments on cell lines and animals.
In addition, it is known that tumor cells are able to deceive the immune system, leaving its field of "vision". One promising area of research is immunotherapy, which is devoted to attempts to block receptors in cancer cells that allow them to pretend to be healthy. If this can be done, malignant cells will be destroyed by the immune system.
Gene therapy for cancer should develop, over time, I think, we will get results that are applicable in practice.