Sleep well
How to stop cancer without harming healthy cells
Kirill Stasevich, "Science and Life", based on the materials of Walter and Eliza Hall Institute of Medical Research: New anti-cancer drugs put cancers to sleep...permanently
A malignant tumor can be put to sleep without interfering with cellular DNA – you can simply turn off the proteins that help cells divide.
Conventional anti-cancer therapies aim to damage the DNA of cancer cells. It can be hard ionizing radiation, as in radiotherapy, or some kind of mutagen substance, as in chemotherapy; in any case, multiple breaks occur in the DNA, with which the cell cannot reproduce - it simply will not be able to copy its DNA correctly for daughter cells, and in general genes with damage will not work they can.
Of course, there are special repair systems, but in cancer cells such systems are often initially damaged – after all, malignant tumors themselves arise due to unrepaired defects in the genome. Drugs and radiation damage DNA even more so that even a cancer cell could not survive.
However, such drugs damage not only cancer, but also healthy cells – the side effects of radiotherapy and chemotherapy can be very, very severe. Here, on the one hand, it is possible to try to organize targeted delivery: to make an irradiation device that could be adjusted strictly to the tumor area, or to make some particles with a medicinal filling that would accumulate only in malignant cells, releasing medicine in them. On the other hand, you can go a different way and act on cancer without destroying DNA.
Cells often degenerate into tumor cells because certain proteins become too active in them due to mutations - usually those that help the cell divide. One of the most well–known such proteins are KAT6A and KAT6B. KAT6A is usually referred to in connection with acute myeloid leukemia, KAT6B is associated with a number of different tumors.
It all starts with the fact that due to chromosomal rearrangements, the KAT6A and KAT6B genes end up on someone else's chromosome, where they do not have the usual regulators and molecular "brakes" - and as a result, they begin to work with such force that they did not work in the same place. The point of their work is to control the activity of other genes.
Without going into details, we recall that DNA in cells is always in a complex with special proteins – histones. Some parts of DNA are heavily packed with histones and are inaccessible to molecular machines that read genetic information; other parts of DNA, on the contrary, are open to work. There are special enzymes that chemically modify histone packers, so that they open DNA to universal access, then close it. And so KAT6A and KAT6B just open up for work those genes on which cell reproduction depends.
Staff The Walter and Eliza Hall Institute of Medical Research, together with colleagues from the University of Melbourne, Monash University and other research centers, have tried in the past to turn off the KAT6A gene itself, and it turned out that with KAT6A turned off, sick animals live four times longer.
But if you still do not interfere with DNA? In a new article published in Nature (Baell et al., Inhibitors of histone acetyltransferases KAT6A/B induce senescence and arrest tumour growth), researchers describe two substances that selectively inhibit the activity of proteins KAT6A and KAT6B – both substances were tested on cell cultures and on animals: fish with liver carcinoma and mice with lymphoma.
In all cases, the malignant cells stopped dividing, as if falling asleep, but this dream turned out to be eternal. The cancer cell, in general, knows nothing else but how to multiply, and everything is aimed at division. If they are forbidden to share, they begin to age: they synthesize fewer proteins, their energy exchange decreases, and biochemical garbage accumulates in them. In aging cells, a program of cellular suicide can be activated – so that the cell dies neatly, without interfering with others; if such a program does not turn on, their immunity destroys them.
So far, the authors have seen how cancerous tumors stop growing and how their cells begin to age. And it is worth noting once again that this was done without spoiling their DNA.
Of course, the question arises how other healthy cells, which also retain the ability to reproduce, like stem cells, will react to such substances that prohibit division.
However, both experimental molecules act reversibly, that is, when the tumor disappears, ordinary dividing cells (if they are also "put on pause") they can return to normal life. However, here you will need a tool that will help get rid of a dormant tumor, so such drugs, if they appear in clinical medicine, will obviously be used with other means – for example, accelerating aging and eating cancer cells by immune.
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