Combined anti-cancer drug
A drug has been created against cancer that is immune to treatment
Scientists at Temple University (USA) have developed a new method of treating cancer tumors that are immune to traditional therapy. The combined drug promotes the accumulation of mutations in malignant cells. An article with the results of the study was published in the journal Cell Reports (Sullivan-Reed et al., Simultaneous Targeting of PARP1 and RAD52 Triggers Dual Synthetic Lethality in BRCA-Deficient Tumor Cells).
One of the reasons for the appearance of cancerous tumors are mutations in specific genes that control the growth and reproduction of cells. These mutations may occur due to a decrease in the activity of BRCA proteins (Eng. breast cancer), which repair breaks that occur in two DNA chains at once. However, at the same time, tumors become prone to accumulate mutations, which, ultimately, could contribute to the death of cancer cells. This does not happen due to alternative DNA repair (repair) mechanisms, such as the enzymes PARP1 and PARP2. These molecules, especially active in tumors, remove single-chain breaks, preventing the appearance of potentially lethal double-chain breaks.
For the treatment of tumors with BRCA deficiency, the drug olaparib, which is a PARP inhibitor, is used. However, the effect of treatment does not last long due to compensatory mechanisms arising from mutations. Such mechanisms include the prevention of drug penetration into the cell or its accelerated removal from it, as well as the activation of additional repair mechanisms, including RAD52 proteins. Scientists have hypothesized that simultaneous suppression of PARP and RAD52 is a more effective way of treatment.
Experiments with cell cultures have shown that the inhibitor RAD52 – 6-hydroxyl-DL-dopa (a derivative of the antiparkinsonian agent levodopa) – suppresses residual repair activity in cells with BRCA deficiency treated with olaparib. The combined use of these drugs increased the accumulation of double-stranded breaks and suppressed the growth of adenocarcinoma cells. After 28 days of drug treatment, the cells with BRCA deficiency completely died. The same effect was demonstrated in the cell line of leukemia and Burkitt's lymphoma.
The new treatment method was tested on a mouse model of chronic myeloid leukemia. Scientists have bred transgenic mice in which, in the absence of tetracycline, tumors with a deficiency of BRCA began to develop for about 70 days. In rodents in which either RAD52 or PARP activity was genetically suppressed, the disease appeared on day 100-120. However, 33 percent of animals in which both proteins were inactive showed no signs of illness for 200 days.
Portal "Eternal youth" http://vechnayamolodost.ru