Tumor necrosis factor (TNF) is a specific protein of a group of cytokines - hormone-like substances produced by the immune system. It is of great interest in medicine due to its properties - the ability to cause cell death (necrosis) of intratumoral tissue. This is a real breakthrough in medicine, allowing the use of drugs with TNF for the treatment of cancer.
Discovery history
By the beginning of the 20th century, a pattern was discovered in medical practice: in some patients, there was a decrease and / or disappearance of tumor formations after suffering any infection. After that, the American researcher William Coley began to deliberately inject cancer patients with drugs containing an infectious principle (bacteria and their toxins).
The method was not recognized as effective, as it had a strong toxic effect on the body of patients. But this was the beginning of a whole series of studies that led todetection of a protein called tumor necrosis factor. The discovered substance caused the rapid death of malignant cells implanted under the skin of experimental mice. A little later, pure TNF was isolated, which made it possible to use it for research purposes.
This discovery contributed to a real breakthrough in cancer therapy. Previously, with the help of cytokine proteins, it was possible to successfully treat only some oncological formations - skin melanoma, kidney cancer. But a significant advance in this direction has been made possible by the study of the properties possessed by the tumor necrosis factor. Preparations based on it are included in the chemotherapy procedure.
Mechanism of action
Tumor necrosis factor acts on a specific target cell. There are several mechanisms of action:
- Through special TNF receptors, a multi-stage mechanism is launched - programmed cell death (apoptosis). This action is called cytotoxic. At the same time, either the complete disappearance of the neoplasm or a decrease in its size is observed.
- Through disruption or complete cessation of the cell cycle. The cancer cell becomes unable to divide and tumor growth stops. This action is called cytostatic. Usually, the tumor either stops growing or shrinks in size.
- By blocking the process of formation of new vessels of tumor tissue and damage to existing capillaries. The tumor, deprived of nutrition, necrotizes, shrinks and disappears.
There are situations when cancer cells can become insensitive to administered drugs due to mutations. Then the mechanisms described above do not arise.
Medical use
Tumor necrosis factor is used in the 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 for people with concomitant pathologies - cardiovascular, renal, hepatic. Recombinant tumor necrosis factor is used to reduce toxicity.
Treatment with cytokines is a new and progressively developing direction in oncology. At the same time, the use of TNF is considered the most effective. Since this substance is highly toxic, it is used by so-called regional perfusion. The method consists in the fact that an organ or part of the body infected with a tumor is isolated from the general blood flow with the help of special equipment. Then artificially start blood circulation with the introduced TNF.
Dangerous Consequences
Tumor necrosis factor is used with caution in medical practice. A number of studies prove that TNF is a key component in the development of sepsis, toxic shock. The presence of this protein increased the pathogenicity of bacterial and viral infections, which is especially dangerous in the presence of HIV in a patient. It has been proven that TNF is involved in the occurrence of autoimmune diseases (for example, rheumatoid arthritis) in which the immune system mistakenlytakes the tissues and cells of his body for foreign bodies and damages them.
To minimize high toxic effects, the following measures are observed:
- use only locally at the site of tumor formation;
- combined with other drugs;
- work with mutant less toxic TNF proteins;
- inject neutralizing antibodies.
These circumstances force the limited use of tumor necrosis factor. Their treatment should be well organized.
Diagnostic indicator
A blood test does not register TNF in a he althy body. But its level rises sharply in infectious diseases, when pathogen toxins enter the bloodstream. Then it can be contained in the urine. Tumor necrosis factor in the joint fluid suggests rheumatoid arthritis.
Also, an increase in this indicator indicates allergic reactions, oncological diseases 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 injuries and burns, conditions are created that reduce the tumor necrosis factor. An immunosuppressive drug would have a similar effect.
Drugs
TNF-based drugs are called targeted - capable of acting on a specific molecule of a cancer cell, causing the death of the latter. Atthis effect on other organs remains minimal, which reduces the toxicity that tumor necrosis factor has. TNF-based drugs are used both independently (monotherapy) and in combination with other drugs.
Today there are several TNF-based funds, namely:
- NGR-TNF is a foreign drug whose active ingredient is a TNF derivative. Able to damage the vessels of the tumor, depriving it of nutrition.
- "Alnorin" is a Russian development. Highly effective in combination with interferons.
Refnot is a new Russian drug containing tumor necrosis factor and thymosin-alpha 1. Its toxicity is extremely low, but its effectiveness is equal to natural TNF and even exceeds it due to its immunostimulating effect. The drug was created in 1990. It successfully passed all the necessary clinical trials and was registered only in 2009, which gave official permission for the treatment of malignant neoplasms.
Self-administration of any drugs based on tumor necrosis factor is strictly prohibited. Cancer treatment is a complex process that takes place exclusively under the supervision of a specialist.
