Necrosis factor of tumors: drugs

The tumor necrosis factor (TNF) is a specific protein of a group of cytokines - hormone-like substances produced by the immune system. It causes great interest in medicine due to its properties - the ability to cause cell death (necrosis) of intracellular tissue. This is a real breakthrough in medicine, allowing the use of drugs with TNF for the treatment of cancer.

History of the discovery

By the beginning of the 20th century, a regularity was found in medical practice: in some patients the tumor formations decreased and / or disappeared after the transmission of any infection. After that, the American researcher William Coley began deliberately to introduce oncology drugs containing the infectious origin (bacteria and their toxins). The method was not recognized effective, as it had a strong poisoning effect on the patient's body. But this was the beginning of a number of studies that led to the discovery of a protein called the tumor necrosis factor. The detected substance caused the rapid death of malignant cells implanted under the skin of experimental mice. A little later, pure TNF was isolated, which allowed using it for research purposes.

This discovery contributed to a real breakthrough in the treatment of cancer. Previously, with the help of protein-cytokines, it was possible to successfully treat only some oncological formations - melanoma skin, kidney cancer. But much progress in this direction has allowed the study of the properties that the tumor necrosis factor possesses. Preparations based on it are included in the chemotherapy procedure.

Mechanism of action

The tumor necrosis factor acts on a specific target cell. There are several mechanisms of action:

• Through a special TNF receptor, a multi-stage mechanism is triggered-programmed cell death (apoptosis). This action is called cytotoxic. In this case, either a complete disappearance of the tumor or a decrease in its size is observed.
• Through the violation or complete cessation of the cell cycle. The cancer cell becomes incapable of division and the growth of the tumor ceases. This action is called cytostatic. Usually, the tumor either ceases to grow or decreases in size.
• By blocking the formation of new vessels of tumor tissue and damaging the already existing capillaries. A tumor deprived of nutrition is necrotic, decreases and disappears.

There are situations where cancer cells can be insensitive to the drugs being administered due to mutations. Then the above mechanisms do not arise.

Use in medicine

The tumor necrosis factor is used in so-called cytokine therapy - treatment with specific proteins produced by blood cells responsible for immunity. The procedure is possible at any stage of the tumor process and is not contraindicated to people with concomitant pathologies - cardiovascular, renal, and hepatic. To reduce toxicity, recombinant tumor necrosis factor is used.

Treatment with cytokines is a new and progressively developing trend in oncology. In this case, the use of TNF is considered to be the most effective. Since this substance is highly toxic, it is used by so-called regional perfusion. The method is that a tumor-infected organ or part of the body is isolated from special equipment by means of special equipment from the total blood flow. Then, blood circulation with injected TNF is artificially triggered.

Dangerous consequences

In medical practice, the tumor necrosis factor is used with caution. A number of studies prove that TNF is a key component in the development of sepsis, toxic shock. The presence of this protein enhanced the pathogenicity of bacterial and viral infections, which is especially dangerous in the presence of HIV in the patient. It is proved that TNF is involved in the occurrence of autoimmune diseases, (for example, rheumatoid arthritis) in which the immune system mistakenly takes tissues and cells of its body for foreign bodies and damages them.

To minimize the high toxic effect, the following measures are taken:

• Use only locally at the site of tumor formation;
• Combine with other drugs;
• Work with mutant less toxic TNF proteins;
• Neutralizing antibodies are introduced.

These circumstances force a limited use of tumor necrosis factor. Treatment should be properly organized.

Diagnostic index

A blood test does not detect TNF in a healthy body. But its level rises sharply in infectious diseases, when toxins of the pathogen enter the bloodstream. Then it can be contained in the urine. The tumor necrosis factor in the joint fluid speaks of rheumatoid arthritis.

Also, an increase in this indicator indicates allergic reactions, cancer and is a sign of rejection of transplanted donor organs. There is evidence that an increase in this indicator may indicate non-communicable diseases, for example, heart failure, bronchial asthma.

With various immunodeficiencies (including AIDS) and severe viral diseases, as well as trauma and burns, conditions are created that reduce the tumor necrosis factor. A drug that has an immunosuppressive effect will give a similar effect.

Preparations

Preparations based on TNF are targeted - capable of acting on a specific molecule of a cancer cell, causing the death of the latter. At the same time, the effect on other organs remains minimal, which reduces the toxicity that the tumor necrosis factor has. Preparations based on TNF are used both independently (monotherapy) and combined with other drugs.

Today there are several means on the basis of TNF, namely:

• NGR-TNF is a foreign preparation whose active substance is a derivative of TNF. It is able to damage the vessels of the tumor, depriving it of food.
• "Alnorin" is a Russian development. Highly effective in combination with interferons.

"Refnott" is a new Russian drug containing tumor necrosis factor and thymosin-alpha 1. Its toxicity is extremely low, but the effectiveness is equal to natural TNF and even exceeds it due to immunostimulating action. The drug was created in 1990. It successfully passed all the necessary clinical trials and was only registered in 2009, which gave the official permission for the treatment of malignant neoplasms.

Self-administration of any drugs based on tumor necrosis factor is categorically prohibited. Treatment of cancer is a complex process, which takes place solely under the supervision of a specialist.