05 February 2024

Biochemists have developed a drug that targets cancer destruction

French scientists have created a substance that has several effects on tumors. It is based on short double-stranded RNA, provokes inflammation, immune response and death of cancer cells by apoptosis. The drug also stops the cell cycle in the neoplasm, and the antibody in the compound binds to oncogenic signaling - potentially allowing the substance to be administered intravenously.

There are many varieties of cancer therapy, ranging from surgery and chemotherapy to the use of viruses and drugs that disrupt the growth of malignant tumors. All methods have their own advantages and disadvantages - there are many oncologists working to eliminate them. One of these improving directions can be called immunotherapy - when doctors artificially stimulate the human immune system to fight cancer.

The principle of the method is that a molecular drug based on short double-stranded RNA (dcRNA) provokes local inflammation around the tumor, activating the immune response receptor RIG-I. Following this, immune cells (T cells) produce inflammatory cytokines - signaling molecules. There are several experimental drugs that act on this principle, but their main problem is the intratumoral method of administration - it is not the most effective (in some cases, the tumor is located in such a way that it is very difficult or impossible to regularly inject the drug into it), because it can introduce difficulties in clinical trials.

French biochemists have developed a new drug that combines activation of the receptor RIG-I and disabling the protein PLK1, which protects chromosomes from separation - earlier Naked Science wrote about its discovery. The drug itself, according to the authors, could be administered intravenously. The scientific work was published in the journal iScience.

The innovative drug is a structure conjugate-antibody-dcRNA - it was called siPLK1-5′-ppp RNA. To deliver it to the neoplasm, the scientists chose an antibody that binds to the EphA2 receptor, which can, under different circumstances, both promote cancer growth and inhibit it. EphA2 accumulation is oncogenic signaling, and proteins that respond to this receptor seemed an attractive drug delivery vehicle to the researchers.

Activation of another receptor, RIG-I, triggers the process of apoptosis, that is, programmed cell death, in cancer cells. Compared to another death scenario - necrosis - apoptosis is much safer because it does not cause severe damage to the cell, and in the body, additional inflammation.

Together with disabling PLK1, that is, stopping further cancer cell division of completed DNA replication, the researchers claim that the synergistic effect of the substance can trigger a strong immune response and tumor degradation. The biochemists also envision intravenous use of the new agent - an antibody that responds to the EphA2 receptor could target the drug to the tumor without targeted injections.

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