Glioblastoma - a malignant brain tumor that develops rapidly. On average, after put the terrible diagnosis, the patient lives a few months - no more, and any attempt to treat not give positive results. So that patients with glioblastoma therapy is usually reduced to radiolecheniyu and receiving Temozolomide drug. Other pharmacological agents now just does not exist.
I must say that the work on the creation of targeted drugs in this area has been going on for a long time, but significant results so far no. Although scientists hope is still not lost: the Americans, for example, we have discovered a molecular mechanism that promotes the growth and development of aggressive glioblastoma. Blocking in an experiment this mechanism, the researchers even managed to halt the growth of cancer in the minds of laboratory animals.
To find the genes that contribute to / hamper the development of glioblastoma, some time ago, experts from Massachusetts Institute of Technology (USA) was used shRNA-technology (so-called "techno small hairpin RNA ").
"Structure" short RNA molecules can bind to a portion of the DNA sequence of a particular gene, deactivating it. And thus it becomes possible to "turn off" the genes sequentially, in order to find out for sure, as the activity of any one of them affects the growth / development of a malignant swollenOli.
The experiments also revealed: glioblastoma growth stops, if the "switch off" the gene encoding protein PRMT5, joins a methyl group to a DNA portions of various genes. Communication of this enzyme with cancer was already known, but it was unclear how it stimulates the growth of cancer cells.
Further studies led to the hypothesis that PRMT5 promotes tumor growth by participating in one of the splice. Indeed, when the transferred genetic information from DNA to messenger RNA, first an intermediate type RNA comprising introns - sections, which then simply "cut" (this procedure is called splicing), and then mRNA was simply unable to leave the nucleus and reach the cytoplasm to synthesize squirrel.
In 2015 by experimental studies it was found that mRNA splicing in 10-15 percent of all cases do not pass through: it stops at residues 1-3 introns. And scientists believe such mRNA - "rapid reaction tank." Activate RNA comprising one intron, it is possible in one step. It has been well established: PRMT5 involved in the removal of such "nedorezanny" introns and rapid activation of the genetic pool of mRNA for proteins involved in cell proliferation.
It seems that undifferentiated stem cells of nervous tissue have a high level of PRMT5, as for brain development need a lot of these proteins. As cells mature, the need for such proteins drops and decreases PRMT5 level, but the level of "reserve" of mRNAs encoding proteins of proliferation increases. But brain cells, reborn into cancer, gain characteristics of immature, undifferentiated. This shows just an increase PRMT5-level, which stimulates protein synthesis and cell proliferation, thus activates the growth of malignant tumors.
This little to say and write, but inhibitors PRMT5 still there. One such drug is already being tested clinically on cancer patients. Not long ago, the same scientists said: developed inhibitors being transplanted under the skin of experimental mice, stop growth of glioblastomas. However, most of these compounds, unfortunately, does not overcome the blood-brain barrier, which protects the human CNS. But the researchers hope to develop drugs that will be able to cross this barrier.
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