Anthrax against cancer

Alexandra Bruter, Polit.<url> based on ScienceDaily: Chemists recruit anthrax to deliver cancer drugsScientists from the Massachusetts Institute of Technology borrowed from anthrax a method of delivering cancer drugs into cells.

They described their research in the journal ChemBioChem (Liao et al., Delivery of Antibody Mimics into Mammalian Cells via Anthrax Toxin Protective Antigen).

Some cancer cells, especially cells of some types of breast cancer, have receptors for epidermal growth factor receptor (EGFR) on the surface. Stanley Cohen and Rita Levi-Montalcini received the Nobel Prize in Physiology or Medicine in 1986 for the discovery of this growth factor. The receptor for this growth factor is located on the surface of many healthy cells. When the receptor is non-functional due to a mutation, a person usually has problems with skin, hair and digestion.

Let's look at how this system functions. There is a receptor sitting on the surface of the cell, a girl in a dungeon, a scythe on the street. Part of the molecule is inside the cell, part is outside. Some other cell secretes a molecule of endothelial growth factor into the intercellular space, it gets to the receptor and binds to it. In this case, the intracellular part dissociates and goes free swimming through the cytoplasm. This part can get into the core. In the nucleus, it can bind to a certain DNA sequence and start the synthesis of the matrix RNA of the desired genes. Intercellular dialogues on a variety of topics look one way or another, only the molecules involved in them are different. The epidermal growth factor instructs cells to grow and multiply.

Signaling cascades triggered by receptors for epidermal growth factor (scheme of wikipedia.org – VM)

In a cancer cell, a mutation may occur in the DNA region that regulates the number of EGFR receptors. From this, the cell will immediately have an advantage – it will be able to grow faster. Therefore, some cancerous tumors really consist of cells that have EGFR receptors on the surface, although they are not supposed to. It is possible to make an antibody molecule that would bind to the EGFR receptor, but would not trigger further events. Such an antibody is, for example, herceptin, a drug known under the commercial name "Transtuzumab", which is used against breast cancer and stomach cancer. Some other cancer drugs are also antibodies that interact with molecules located on the surface of cancer cells.

The trouble is that there are many growth factors, and not all of their receptors are on the surface of the cell, some float freely in the cytoplasm. There are other proteins active inside the cell that help cancer cells multiply rapidly. Antibodies to them could also become medicines. But growth factors easily penetrate the cytoplasmic barrier, and antibodies are not capable of this at all. By themselves, even antibody simulators do not penetrate into the cytoplasm – synthetic molecules of a smaller size, not similar in structure to real antibodies, but interacting with proteins on the same principle. It is this problem that scientists have learned to solve by borrowing experience from the causative agent of anthrax.

Anthrax bacilli have long learned to deliver their proteins inside the cells. They have a special toxin for this. Scientists neutralized this toxin, added antibody simulators to it, and the whole structure turned out to be able to get into cells.

Anthrax toxin consists of three main components. The first is the so–called protective antigen. It binds to one of the receptors present on the surface of almost all human cells. When the protective antigen is fixed on the surface, two other proteins join it – edematous antigen and lethal antigen. At the same time, a pore forms in the cell membrane, and the last two crawl inside and harm there. As a rule, their actions lead to cell death. But they can cut off the part that is responsible for the harm and even replace it with antibodies or antibody simulators.

This design of the authors of the work was able to penetrate the cells. When tested on cancer cells, it caused a mortality rate of 20% of the cell mortality rate during treatment with imatinib. This result is explained by the fact that the imatinib molecule is not a protein, it is smaller in size, and, accordingly, it is easier to achieve a higher concentration of it. Imatinib, although not a protein, interacts with the target protein in cancer cells on the same principle as antibodies. But it is more difficult to select non-protein molecules with such properties than protein ones.

It should be understood that this is only the beginning, and further research will increase the effectiveness of such drugs. In the described work, a universal mechanism is proposed, a solution to a fundamental problem – how to help a protein molecule get into a cell. This will make it possible to develop not only drugs against cancer, but also, for example, antiviral drugs, the need for which is very strong in today's world. It will be enough to send inhibitors of proteins involved in the life cycle of the virus to the cells.

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