Children's tumor cells will be prevented from repairing DNA
Pediatric oncologist Alex Kentsis and his colleagues have proposed a new method of combating tumors in children, which is based on a violation of the mechanisms of DNA repair in tumor cells. The drug they found showed its ability to stop the growth of tumors. This does not cure cancer, but stops the development of the disease and allows you to effectively fight it with other means.
Tumors in children are often different from adult tumors. They are caused by different mutations and react differently to the same drugs. Therefore, it is not surprising that over the last quarter of a century, more than a hundred drugs have been registered in the United States to fight adult tumors and only four for the treatment of tumors in children.
Scientists in the laboratory of Alex Kentsis noticed that many childhood tumors actively produce the protein PGBD5, which is capable of causing mutations in cancer cells. In most healthy cells, both in children and adults, the gene responsible for this protein is inactive and its function in a healthy body is unclear. The researchers also found that tumor cells containing a lot of PGBD5 are helped to survive by the active work of DNA repair mechanisms – various ways to repair damage in this molecule.
Kentsis and his team decided to block DNA repair in tumor cells. They picked up five molecules, which, according to their calculations, should have prevented the passage of signals to the beginning of DNA repair, and tested them in cultures of ordinary cells modified in such a way that the PGBD5 protein gene worked for them. As a result, they selected the most promising substance, which received the designation AZD6738. It stopped DNA repair, eventually causing the death of 80% of cells.
Then this substance was already tested on tumor cell cultures. The researchers selected four types of tumors that occur in children: Ewing's sarcoma, neuroblastoma, medulloblastoma and rhabdoid kidney tumor. They found that, compared to normal cells, the cells of all four types of tumors were more vulnerable to the drug AZD6738. But if scientists turned off the production of the PGBD5 protein in tumor cells, the drug became less effective.
At the next stage of the study, cells of the same four types of tumors were transplanted into laboratory mice. Then the mice received injections of AZD6738. As reported in an article published by the journal Science Translational Medicine, the experiment showed effective suppression of the growth of two tumors: neuroblastoma and medulloblastoma. It does not provide a complete cure, but stops the development of the tumor. Now Alex Kentsis and his colleagues plan to start clinical trials of the drug. In addition, AZD6738 is already being tested to test its ability to stop the growth of mammary gland tumors.
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