Rapidly changing oncology
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Denis KUROV, "Movement against Cancer" – especially for OPEC.RUGrow to kill
Scientists have long been interested in why this or that type of cancer occurs and how it can be affected without destroying healthy cells of the body.
Billion-dollar investments, a colossal scientific base, more than two decades of work ... Modern drugs for the treatment of oncological diseases have fundamental differences from those that appeared on the market in the 1970s.
Breast cancer is the leading cause of death from cancer in women. Breast cancer patients with a positive HER2 status have a poor prognosis and low survival (1-2 years from the moment of diagnosis), including because a tumor with a positive HER2 status does not respond to traditional chemotherapy lines. Women of reproductive age are particularly susceptible to the disease.
Mortality from breast cancer in the last 8 years:
in Russia it increased by 13 %,
in the USA it decreased by 23 %,
in England, it decreased by 20%.
How to turn off the receptorFor many years, scientists have been trying to determine on a specific type of tumor disorders in the organ that can be affected.
For example, breast cancer is a tumor that arises from cells of the same type. On the surface of these cells, among all others, there are receptors of the type NR (human epidermal growth factor receptor). They began to study them, determined that there are four types of receptor, one of which – NONR2 (the second type) – plays a key role in the vital activity of a normal cell.If you "turn off" the receptor, the cell dies.
The transmission of signals through receptors is a means of communication of cells with the outside world and vice versa. Cells communicate, receive signals. Normal cells are under the pressure of the external environment, a ban on uncontrolled reproduction. Roughly speaking, otherwise people would grow not two, but four hands and so on. The human body is a self–regulating system, some cells die, others are born.
– If we compare a normal and a tumor cell, then, in principle, they do not differ in anything special, – they say in the Moscow representative office of the Swiss pharmaceutical concern "Roche". – But in the tumor one "switch" failed. Tumor cells lose the ability to perceive signals from the outside, become uncontrollable, they have only one goal – to multiply.
Find and destroyRoche was the first to create drugs based on so-called monoclonal antibodies.
The company sponsored long-term and expensive research, in particular, to study the molecular mechanisms of disease development. For example, the development of drugs such as mabthera and herceptin (also known as trastuzumab) took about 25 years.
These monoclonal antibodies themselves find a certain type of cancer cell, attach to it and destroy it. They can also carry a radioactive molecule that will direct radiation directly into the cancer cell. This is called targeted impact (from the English "target" – goal). Antibodies are aimed at interacting only with certain parts of the cell – receptors that are located on the surface, like small antennas.
The antibodies themselves are quite normal for the human body – most of them are immunoglobulin molecules, which are already present in the body. These are proteins that are activated at the moment of the immune response of the human body to the occurrence of a foreign agent.
What's happening? A monoclonal antibody is like a native for the body, it causes reactions to itself. But at the same time, it seems to bind the receptors of cancer cells, which makes the body instantly perceive the formation as an alarm signal. An immune response occurs, and the tumor is destroyed by the body.
What is the fundamental difference between the new class of drugs? Traditional chemotherapeutic drugs killed, in addition to the tumor, and normal cells. There are drugs that stop the cell cycle at a certain stage, and the cell is destroyed. But, unfortunately, they do not distinguish tumor cells from healthy ones… Hence the undesirable consequences against the background of various types of chemotherapeutic treatment.
Humans and MiceThe study and discovery of monoclonal antibodies that stop tumor growth took the company about 15 years.
"When we started working on this topic, we did not yet know what the research would lead to," the researchers admit. It took about seven more years to develop a monoclonal antibody based on human and mouse immunoglobulin. In the case of herceptin – mouse, which, on the one hand, was not rejected by the body, on the other, could specifically interact with NONR2 receptors. A lot of scientists around the world were involved in the long experiment.
Then the period of preclinical studies begins. After a positive result, clinical trials begin – four stages, strictly regulated rules. Finally, after determining the dose of the drugs, the phase of studying the drug begins specifically for women suffering from a NON-R2-positive form of breast cancer, which accounts for up to 20-30% of all tumors of this localization.
Risk as salvationBy the way, participation in such a study saved the life of Natalia Shestakova, now a member of the initiative group of the Movement against Cancer.
When this type of cancer was found in her a few years ago, they refused to operate on her – it was too late. And Natalia agreed to participate in the herceptin study. She is cured, lives, helps other women who are in trouble.
According to the results of positive tests, the drug was registered (in Russia – in 1999). After that, during the post-registration phase, patients receiving the drug were monitored. As with other drugs, all side effects, contraindications, interactions with other drugs are listed in the instructions.
Love yourself a littleHow much does treatment with innovative drugs cost?
They are expensive because the manufacturing process itself is complicated. For example, a one–year course of herceptin is 1.8 million rubles. The production cycle of the drug is approximately seven months. Monoclonal bodies are grown like crystals on a culture of special cells. Conditions, packaging, short shelf life – all this gives a high cost and ... life.
– Due to the high cost of the drug, before the benefits appeared in Russia, its sales volumes were insignificant, – the company says. – With the advent of state financing, since 2005, we have recorded a significant increase in sales. It is absolutely proven that early adequate administration of the drug can save a woman's life and cure her of a terrible disease. Among the participants of the "Movement against Cancer" there are those who were diagnosed and treated in time, although, according to all forecasts, if there was no medicine, they would no longer be alive.
Having reached this topic, drug developers immediately begin to talk about the enormous importance of early diagnosis. This, they add, is Russia's main problem. After all, there are cases when patients come to the doctor already at the stage of tissue destruction! A woman herself should be checked, undergo mammography (starting from the age of 35, doctors advise all women to do this annually). But no less important is the issue of determining the HER2-positive stage. Moreover, the HER2-positive tumor does not respond to other types of treatment. From traditional chemotherapy, for example, it becomes more aggressive, grows even faster…
If we talk about the metastatic form of the disease (it is believed that there are from 10 to 12% in the entire field of diagnosed tumors), then the most effective combination is herceptin + docetaxel (from the group of drugs - taxanes).
MMM – the method of small moleculesCurrently, all pharmaceutical companies are moving towards the development and production of targeted drugs.
"Oncology has become a priority area for many pharmaceutical companies in recent years," Roche adds. – Thanks to science, the nature of diseases has become clearer, the human genome has been deciphered, it becomes clear which mutation of genes leads to what consequences, signaling pathways in the body have been found… Many drugs of the so-called small molecule group are being developed now. The molecules penetrate into the cell and bind from the inside to the HER2 receptor. Thus, another mechanism of blocking receptors is manifested.
Figuratively speaking, the receptor is like a float, the upper part of which catches external signals. Herceptin covers the "float" like an umbrella, and small molecules "dive" into the cell. Other drugs are also being developed. But due to the fact that the nature of a particular oncological disease has not been studied accurately enough, it is not yet possible to give drugs the targeting characteristic of monoclonal antibodies.
However, you won't learn much from the corporation at the development stage. Her research is an object of the highest degree of secrecy. The colossal work done by companies becomes known only in the case of discovery and achievement. So, Novartis has an outstanding drug glivek for lifelong therapy of one of the types of oncological diseases. Pfizer has an innovative drug on the way. Sanofi-Aventis and Astra-Zeneka are also among the leaders of pharmaceuticals in the field of oncology…
And what about Russia? If we talk about the preclinical part and the development of drugs, then Russia has a very weak position. As for participation in clinical trials, on the contrary, Russia is one of the leading countries. By the way, as experience with herceptin shows, for many it becomes the only chance to survive.
Portal "Eternal youth" www.vechnayamolodost.ru11.03.2008