The cancer drug dacarbazine may make melanoma more resistant to drugs. This was reported by the press service of the RNF.
Melanoma is the most common form of skin cancer, but it is also the most dangerous. It is almost impossible to detect in the early stages, and in most cases the problem becomes noticeable only during the formation of metastases. Also, melanoma has many phenotypes, making it easy to become resistant to drugs. Finally, this cancer can go into a dormant state where its cells do not divide temporarily and therefore do not secrete DNA.
Researchers at Krasnoyarsk State Medical University and colleagues at other universities have discovered that dacarbazine, a drug used to treat melanoma, can actually make it more resistant to the drug. This drug needs to bind to the cell’s DNA and prevent it from dividing, which has negative consequences.
The authors treated melanoma cultures with dacarbazine and then examined the activity of their genes. It turned out that the number of dividing cells decreased by about nine times: they had genes responsible for the transition to the resting state, which can be the result of conditionally irreversible cellular aging or “hiding”. At the same time, there were no clear signs that the cells were aging, meaning they could return to activity.
The drug affected the activity of many genes important for cell life. Thus, signaling pathways related to cell cycle regulation, proteins that protect the integrity of DNA, and molecules that promote germination of blood vessels are disrupted. As a result, cells are more likely to make mistakes that can destroy themselves or make them more resistant to treatment than before. Without blood vessels, cancer cannot grow and metastasize, while the active substance of the drug does not reach it. Treatment with dacarbazine contributed to the majority being immobile among the cells most capable of binding to surfaces, so the so-called subject-astatic pool may have formed. Such a pool is protected from therapy, as it interacts with the body in a non-standard way.
In the future, the authors will try to find out if cancer cells in this state have a vulnerability and, if so, how to destroy it.
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