"Trojan horse" for cancer
Paclitaxel is a chemotherapeutic drug that rapidly suppresses the proliferation of cancer cells. Maurizio Pellecchia and his group have developed a new drug delivery method to block the migration of cancer cells outside the primary tumor.
Researchers have identified the goal of therapy – a protein oncogene EphA2 (ephrintype-A receptor 2), which promotes the migration of cancer cells into the blood and spread throughout the body. They decided to place the paclitaxel molecule on the peptid123B9, which binds to EphA2 and can act as a "Trojan horse". Without 123B9, paclitaxel is unable to reach the EphA2 protein.
Schematic representation of the agent blocking metastasis. On the right: peptide 123B9 with two "hands" at the bottom, which bind to the protein EphA2, and a molecule of the chemotherapeutic drug paclitaxel at the top. Left: binding of the agent to the cancer cell through interaction with the protein EphA2 (marked in red) on its surface. Source: Pellecchia lab, UC Riverside.
Metastases are the most common cause of death in cancer patients. There is currently no specific treatment aimed at the metastasis process, but many laboratories around the world are working to solve this problem.
Pellecchia and his colleagues found that when the peptide 123B9 binds to the protein EphA2, it penetrates into the cancer cell, releasing the paclitaxel molecule. The cell is dying. Thus, the process of metastasis is inhibited.
Experiments conducted on mouse models of human breast cancer showed that the administration of paclitaxel placed on the peptide 123B9 significantly reduced the number of cancer cells circulating in the blood. The method was more effective than the isolated administration of paclitaxel, and was superior to the control group that did not receive any treatment.
A decrease in the number of circulating cancer cells led to a decrease in the risk of metastases. Thus, in the paclitaxel group with 123B9, mice had almost no cases of lung metastases, while in the other two groups there were many of them.
As the authors of the study write, before the method of preventing metastases is introduced into oncological practice, it will have to pass more than one test. In addition, it is necessary to test more selective and safe chemotherapeutic drugs with fewer side effects compared to paclitaxel.
Nevertheless, the proof of the basic concept has been obtained, with some support and efforts it can be transferred from an experimental environment to clinical practice for the treatment of various types of cancer, including breast, lung, prostate, pancreas and ovaries.
Article by A. F. Salem et al. A potent EphA2 agonistic peptide-drug conjugate reduces circulating cancer cells and metastases in breast cancer models is published in the Journal of Medicinal Chemistry.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru According to UCR Today: Researchers Use a Molecular Trojan Horse to Deliver a Therapeutic Drug to Cancer Cells.