Cellular leaf fall
Does cancer prevent a person from gaining immortality?
Can a person live forever, how are tumors and aging related, will humanity ever be able to completely get rid of cancer? Boris Zhivotovsky, a professor at Moscow State University and Karolinska Institute, as well as one of the largest experts in the study of cell death and cancer.
Photo: MSU press service
Last week Boris Davidovich gave a lecture at the Moscow festival "Science 0+", held at the Lomonosov Moscow State University. He spoke about how disorders in the work of apoptosis and other mechanisms of "programmed cell death" are associated with the development of cancer, and how some of them can be used to fight tumors.
For example, he explained how the various gene chains that help cancer cells to divide indefinitely work, and how they protect them from chemotherapy and immunity. Blocking the genes associated with them, as many scientists hope, will make cancer less invulnerable and increase the effectiveness of chemotherapy.
In particular, the experiments of scientists from Moscow State University revealed several interesting relationships between the life of cancer cells and breakdowns in genes that directly control the operation of various "programmed death" systems. Many of them, for example, the family of "death proteins" Bcl-2, turned out to be not assistants, but one of the main obstacles to the work of chemotherapy.
Experiments with another important part of this system, the "protein of life" Mcl-1, helped Zhivotovsky and his team understand how cancer cells use cellular waste recycling systems to neutralize chemotherapy and destroy molecules that cause them to self-destruct. Its suppression, as it turned out, can also simplify the fight against cancer and save the lives of patients.
– The Nobel Prize was awarded this year for the discovery of one of the methods of cancer immunotherapy. When can we expect the appearance of the first therapies based on "cellular hunger"?
– It's too early and very difficult to talk about it. I am wary of such statements, since in each specific case of cancer development it is necessary to apply and take into account something of my own.
I will give one example. About 15 years ago, the third phase of clinical trials of a drug designed to combat lung adenocarcinoma was completed in Japan. The results were very encouraging – about 30% of patients responded to this substance.
This is a stunning result, especially considering that it was used without combination with other types of chemotherapy – with them the result was even better.
Based on these results, the American FDA approved the use of this medicine in The United States. When doctors started using it, it turned out that in the best cases it helped only 2% of Americans.
What happened? The "failure" was due to the fact that the drug was "tuned" to a certain mutation that often appears in East Asians, but it is almost absent in Europe or America.
Therefore, we always have a question – is this a good drug or a bad one? Of course, he is good, but we must understand that he helps only a certain group of patients. All this suggests that we urgently need personalized medicine, an individual approach to each patient and each tumor.
As for programmed cell death, we can say that such drugs already exist and that many of them have already been approved by the FDA. Today they are used in clinics for the treatment of hematological tumors. So, the first substances, the so-called BH3-mimetics, were created. They are already actively used in practice, for example, for the treatment of B-cell lymphoma.
The approaches developed by the last Nobel laureates are successfully used in the fight against melanoma and adenocarcinoma of the lungs.
This is a colossal achievement, since until recently the latter was considered incurable. In the case of melanoma, approximately 6-7 out of 10 patients respond to combined treatment, and in the case of adenocarcinoma – from 4 to 5. Obviously, there is a huge difference between the zero that we had before and 4-5 saved patients.
– At the lecture, you talked about a huge number of possible violations in the operation of "programmed death" systems. Is it possible to create a retrovirus that would simply insert a complete copy of it into cancer cells and cause them to self-destruct?
– It seems to me that it will be very difficult to do from a technical point of view. I know that in Russia has groups of scientists, for example, the team of Peter Chumakov from Institute of Molecular Biology of the Russian Academy of Sciences, dealing with oncolytic viruses.
I recently read about his achievements, he says that the first such viruses will appear in a few years at best with very good luck on their part. This is a very difficult task, the solution of which will require very painstaking, long and large-scale work. I sincerely wish them success.
In general, all genetic approaches, unfortunately, are very difficult to implement. For example, if we take CRISPR/Cas9, a popular genome editing system, two articles have recently been published showing that DNA editing can lead to disturbances in the p53 protein and the appearance of cancer cells.
Any genetic intervention in the life of cells cannot be simple by definition. As I have already told you, pharmaceutical companies have wasted billions of dollars on creating short RNA molecules that suppress Bcl-2. Nature, fortunately or unfortunately, is smarter than us, and it will not be easy to deceive her.
– Experiments on calorie restriction show that cells switch to a different mode of life and begin to process garbage more actively when there is a lack of food, which, as you have shown, also affects cancer cells. Is there a connection between metabolic rate and chances of getting cancer?
– Colossal work is currently underway in this area. At the beginning of October, we held a major conference in St. Petersburg, where three reports were devoted to cancer metabolism at once. We learn something new and important almost every day, linking cancer and metabolism.
What is most interesting, all this progress is based on data obtained back in the thirties and forties of the last century, when biologists were just beginning to study the metabolism of ordinary cells. And now it turns out that all this can be used in the study of the characteristics of tumor cells.
– Do we transfer the "experience" of naked diggers and other long-lived animals to humans?
– Interesting experiments in this area are conducted by Vadim Gladyshev from Harvard, who currently also works at Moscow State University. However, so far we can only say that a lot of work and research awaits us here before we find the answer to this question.
– Recently, scientists have conducted several experiments to remove aged cells from the body of mice and have achieved impressive results. Will it be possible in this way not only to prolong life, but also to protect yourself from cancer?
– This area of science, as our conference showed, is developing as fast as the study of cancer cell metabolism. It seems to me that the first, very impressive results in this area will appear in the very near future.
– On the other hand, there are many ideas for telomere lengthening and cell rejuvenation, including with the help of questionable herbal preparations. How safe is all this for a person?
– All this is very dangerous, and it is necessary to treat all such initiatives with great caution. There is no need to go far for an example of the consequences. China has now invested a lot of money in similar research on cancer and traditional medicine.
Many laboratories are now engaged in the fact that they take such drugs and disassemble them literally by atoms and molecules. Someone really succeeds, and someone is engaged in real charlatanism. Such cheating is not always obvious when reviewing such works.
A similar situation has developed with telomeres. We do not know all the consequences of what the activation of telomerases will lead to, and you, alas, have not yet received clear answers from people who create another "means to prolong life".
I know quite well Elizabeth Blackburn, Carol Grider and Jack Shostak, who received the 2009 Nobel Prize in Physiology or Medicine for the discovery of telomeres and telomerase. Shostak has left this field altogether, Blackburn is investigating the structure and functions of telomeres outside of oncology, and Grider continues to investigate the activity of telomerases.
– In recent years, there have been more and more discussions that cancer will soon become the main limiter in human life expectancy. Is this the case and is it possible to find some kind of balance between the rate of aging and protection from cancer?
– I will put this question differently – is there a perpetual motion machine? Of course not! Another thing is that we can noticeably improve not only the duration, but the quality of our life. Two centuries ago, people lived for about 30-40 years, and the Egyptian pharaohs passed away at 20 and inherited the throne at 14.
Now, fortunately, even in In Russia, a person can live up to 70 years without serious health problems. Is it possible to increase the average life expectancy? Of course it is possible, but I do not believe that we will live for 200 years even if we find an opportunity to somehow influence the likelihood of developing cancer.
As Academician E.M. Kreps once told me, "there should always be quality." Therefore, it seems to me that it is not life expectancy that is more important, but how long our body can function normally. Like any car, it gradually wears out. Of course, it can be maintained in some kind of working condition for another 10-20 years or some other time, but in any case it is not forever.
I do not think that artificial organs will somehow help solve this problem - it is unlikely that we will be able to replace the whole heart, put an artificial liver or transfer consciousness to a new brain. No one knows who you will be then, and it's better to just live life as efficiently as possible.
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