Resurrection of Novobiocin
The antibiotic novobiocin was able to destroy the "invulnerable" forms of breast cancer
Scientists hope to continue experiments and test its effect on humans
American doctors have discovered that the antibiotic novobiocin, which was actively used in the middle of the last century to fight infections, can be used to destroy the most aggressive forms of breast cancer, which are not affected by other drugs. The results of the study were published in the scientific journal Nature Cancer (Zhou et al., A first-in-class polymerase theta inhibitor selectively targets homologous-recombination-deficient tumors).
"No one doubts the safety of novobiocin, and at the same time this antibiotic can be taken orally, which distinguishes it from many other cancer drugs. We intend to test it in combination with other drugs in experiments on patients whose tumor cells are supposed to be affected by this substance," said Alan D'Andrea from the Farber Institute for Cancer Research (USA).
Breast cancer ranks first in the number of tumors in women. Every year, it affects about 2.1 million women, and about 627 thousand patients die during the same period. There are several different subspecies of malignant breast tumors that occur due to different mutations. To treat each of them, different types of chemotherapy are needed.
In recent years, doctors have begun to pin high hopes on the so-called PARP inhibitors, which can suppress the growth of most aggressive forms of breast cancer resistant to the action of other anti-cancer drugs.
These compounds block the work of the enzymes BRCA1 and BRCA2, which are responsible for correcting mutations in DNA strands. As a result, a lot of damage quickly accumulates in the genome of tumor cells and subsequently they die. This destroys most forms of breast cancer, but some types of tumors have learned to suppress the action of PARP inhibitors.
A few years ago, D'Andrea and his colleagues found out that this was due to the fact that the POLQ enzyme takes over part of the functions of repairing damaged DNA strands. Experiments on cell cultures showed that its increased activity protected cancer cells from death and at the same time accelerated the accumulation of mutations in their genome.
After that, scientists began to look for substances that could suppress the work of POLQ in tumor cells and at the same time would not affect their healthy neighbors. Having gone through a total of more than 23 thousand . already created and used drugs, scientists found that only ten molecules from this list had similar properties.
The most effective and safe of them was the antibiotic novobiocin, which was isolated from microbes of the species Streptomyces niveus in the mid-1950s. It was widely used in medical practice in the second half of the last century until it lost its effectiveness and was replaced by a new generation of antibiotics.
Experiments on cell cultures showed that antibiocin very quickly and effectively destroyed those tumor cells that were not affected by PARP inhibitors and platinum-based drugs, and at the same time it did not cause mass death of healthy breast cells. Scientists have achieved similar results in experiments on mice in whose body fragments of tumors were implanted.
The successful completion of these experiments, as D'Andrea notes, opened the way for clinical trials with the participation of volunteers. Scientists hope that these experiments will confirm the safety of novobiocin and allow them to rid many women of tumors that other drugs could not cope with.
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