Are we treating a tumor or a person?

The theory of the St. Petersburg professor has received international recognition

Anastasia Dolgosheva, St. Petersburg Vedomosti

"We can build universal diagnostics, universal therapy and universal prevention of cancer diseases," Andrei Kozlov, head of the research laboratory of Molecular Virology at the Peter the Great Polytechnic University, said at a press conference in TASS. With a caveat: this is in the future. Clinical trials usually take about twenty years.

The evolutionary mechanism

In fact, the opening is almost 30 years old. Andrey Kozlov, then a graduate student at the Institute of Oncology named after Petrova, then an intern at the National Cancer Institute (USA), suggested that a tumor is not just a pathology, it is one of the tools of evolution. Moreover, the evolution is progressive, "improving".

But, the professor says, the theory needs to be confirmed, and the necessary methods (mainly related to genome sequencing) appeared not so long ago.

Meanwhile, Andrei Kozlov was the first in the country to organize (in 1987) HIV screening and is now working on an HIV vaccine. He published his theory about the evolutionary role of tumors in articles; two books were published, one of which illustrated the theory with the cover itself: a goldfish with a red riding hood. "This is a tumor," the scientist pointed to the cap. A tumor with which, it turns out, many generations of goldfish live quietly.

Now they are talking about the theory again, because in November an article by Andrei Kozlov and colleagues was published in the important journal Scientific Reports (Makashov et al., Oncogenes, tumor suppressor and differentiation genes represent the oldest human gene classes and evolve concurrently) – this can be considered as a sign of recognition.

What's the point. There are about 400 types of cells in the human body: in the eyes, muscles, adipose tissue, etc. Thanks to some we see, thanks to others we hear, and to others we move... All these cells have the same genome, but different cell types use different parts of the genome. The genes associated with each of the cell types are called differentiation genes.

In turn, oncogenes (cancer-causing genes) also have a history of many millions of years. Tumors are spread throughout the evolutionary tree of multicellular organisms, even the oldest sponges have them.

According to the theory of Andrey Kozlov and his associates, oncogenes evolved in parallel with the differentiation genes that give the cell a particular function.

– It turns out that a tumor is a property of developing matter, – the professor comments. – Only now we are beginning to understand that many of our organs originated from a tumor. Why do women most often die from breast cancer, and men from prostate cancer? Because evolutionarily these are the youngest human organs, signs of the tumor from which they originated may appear in them.

Paradox: throughout the life of an organism, a tumor, a mutation is harmful; on the scale of evolution, it is a mechanism for development. According to Kozlov's theory, the genome evolved, new genes appeared, which then informed the cells of new functions, which then led to the appearance of new organs. But initially, the new genes had to work somewhere - this "platform", these additional cell masses, was provided by tumors.

This process continues. Several evolutionarily new genes have already been described in humans, and, as the scientist says, classical genetics cannot explain this: homo sapiens seems to have completed its evolution, and then why evolutionarily new genes? "So there's something going on in us that we don't know."

The professor complains: science and medicine "are looking under the streetlight, because it's light there." That is, they pay attention to those tumors that are obviously dangerous. But early screening programs show that there can be many tumors in the body, and they do not kill the host:

– Here it is necessary to understand: why don't they bother us? I think I know why. Because there are processes of acquiring new functions. We have some functions all the time – related to immunity, etc. I don't know if we will "grow" a new organ, but new types of cells may well appear.

Not to kill, but to convince

Andrey Kozlov's group discovered previously undescribed oncogenes. As explained by academician Nikolai Yankovsky, head of the N. I. Vavilov Institute of General Genetics of the Russian Academy of Sciences, we are talking about genes that exist only in tumor cells; they are not in normal ones. This means that such genes can serve at least as a diagnostic tool.:

– There are about 140 such genes, they are present in all tested tumor cell types. There are another 60 genes that manifest only in some types of tumors.

There is a concept of "oncomarker": substances by which the presence of a tumor is recognized in the body. The difficulty is that there is one marker for one type of cancer, another for another: the necessary marker is not found – the disease is not recognized in time.

– We find markers that work in all tumors! – says Andrey Kozlov.

A set of genes is a "language"; if you know a set of genes in a tumor, you know the language in which you can "negotiate" with a tumor, the scientist explains. "And then we can 'convince' her to behave the way we need to."

In certain areas, science and medicine have already learned to "negotiate" with the tumor. The scientist gives an example: clinicians have already developed an approach according to which the tumor (and with it the whole body) is not poisoned with powerful doses, but smaller doses are used, but under constant control, so that if the tumor begins to grow, the dose is slightly increased. It is called "metronomic adaptive chemotherapy".

– What is our task: to make the patient live – or to kill the tumor? So that the patient lives," the professor comments.

Another example of an "arrangement". In cases of one of the types of leukemia in children, so-called differentiation therapy is used. Previously, this type of leukemia killed almost one hundred percent. Now – almost one hundred percent survival rate.

The third example. Science has revealed a link between the human papillomavirus and some types of cancer. Now getting vaccinated against this virus in adolescence means protecting yourself from several types of cancer.

– This prevention is based on the fact that science knows several genes of the papilloma virus. And we have discovered 200 genes that are specific to all cancers," Andrey Kozlov continues. – What does this mean? That we will be vaccinated at the age of 40, and people will not develop cancer. Many tumors are in a dormant state – it is possible that malignant tumors can be transferred to a controlled dormant state.

When?

This, of course, is the first question: when will the vaccine appear.

There are currently studies on one and a half thousand cancer vaccines in the world. Of these, 16 are based on one of the genes found by Professor Kozlov's group. A gene that, according to the scientist, "works on all tumors."

Tests are underway in the USA. Not in Russia.

– Until we reverse this situation, we will lag behind, – says Andrey Kozlov. – So far, our first question from potential sponsors is whether this has already been done in America? And if not, then it's not interesting. But if we follow the tracks, we'll never catch up. We must go our own way.

Professor Kozlov's theory, as he admits, "can cause irritation among scientific colleagues." But the main obstacle, the scientist says, is not even the arguments against it, but the fact that "no one cares": "Everyone is very comfortable with old ideas, technologies, hypotheses. All pharma, all billions of dollars are working on old ideas. It is very difficult to publish a new idea in the scientific literature!".

To the question: "When?" – Andrey Kozlov answers: "Many oncologists tell me: it will take 50 years to be recognized... Well, actually, more than 20 years have already passed."

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