2014-02-16 12:50:10
For several decades now, it has been well known that cancer, or should we say cancers, are diseases caused by mutations in genes that produce proteins that modulate cell growth. There are two main types of these mutations: those that activate activating proteins and those that inhibit inhibitory proteins. This seems complicated, but it is simply that either the brake or the accelerator of cell growth breaks down. Let’s see.
The proteins that activate cell reproduction are normally “off” and, therefore, the cell does not reproduce. Only when they are “turned on” (that is, the growth accelerator is pressed), is cell reproduction stimulated. A mutation that “turns on” these proteins will therefore activate cell growth.
On the contrary, proteins that inhibit cell reproduction are normally “on” and, therefore, the cell does not reproduce either. Reproduction is slowed down by them. However, a mutation that “turns them off” (that is, spoils the growth brake) may cause cell growth. The first type of genes are called oncogenes (tumor generators); the second, tumor suppressor genes, or anti-oncogenes.
CURE ALL CANCERS
The above makes it clear that to cure all cancers caused by mutations in oncogenes (in this article we will only talk about them), we would “only” have to know what they are, what mutations activate them, and produce specific drugs that block the action of the proteins. mutated, but not that of healthy proteins. The latter is important because the healthy version of the oncogenic proteins would function normally and it would not be beneficial to affect it.
The above is said much more quickly than it is done. In fact, although there have been important advances in the development of antitumor drugs, we are still very, very far from being able to cure cancer with such exquisite precision and selectivity. Let us keep in mind that one of the oncogenes most commonly mutated in numerous cancers until now lacked a specific drug that would block the action of the protein it produces. This is the oncogene called Ras, discovered more than 30 years ago, which produces a protein that functions as an automatic switch for cell growth. It is worth analyzing how it works.
The Ras protein is normally found in the “off” state. In this state, Ras is bound to a molecule called GDP (guanosine diphosphate), similar to one of the nucleotides found in DNA (it would correspond to the letter G), but bound to two phosphates, and not just one as in the case of DNA. If the cell receives an external signal indicating that it should reproduce (a hormone, for example), the signal induces a change in the Ras protein that causes the expulsion of the GDP molecule attached to it, which now allows Ras to bind. to the GTP (guanosine triphosphate) molecule, identical to the previous one, but with one more phosphate. Interestingly, the exchange of GDP for GTP causes the “switching on” of Ras, which sets in motion complicated mechanisms that lead to cellular reproduction.
But, of course, once the hormone disappears and Ras has accomplished its mission, Ras must “turn off.” This is achieved by the Ras protein itself, by itself, since in a chemical reaction activated by itself, it removes a phosphate from GTP and converts it into GDP, thereby “turning off”!
PURCHASE SHUTDOWN
The most common mutations in the Ras oncogene cause the protein, once activated, to be unable to turn itself off, so it always remains “on” and continues to stimulate cell growth. As I have already said, until today we lacked any drug capable of blocking the action of the mutated protein “on”, or of forcing it “off”. Fortunately, a small big step to alleviate this situation has recently been taken by researchers at the University of California, who publish their results in the journal Nature.
Based on data on the three-dimensional molecular structure of the Ras protein, acquired with sophisticated analysis techniques, and based equally on solid knowledge of chemistry (paradoxically, the least appreciated science), researchers are able to synthesize a drug that chemically binds only to the mutated Ras protein, but not to the healthy protein.
As we have said, the mutated Ras protein has lost the ability to “turn off” on its own, that is, it cannot remove phosphate from GTP to convert it into GDP. Well, the drug, by binding to this mutated protein, causes it to expel GTP and bind to GDP found in the environment, thereby acquiring the “off” state independently of its ability to remove the phosphate left over from GTP to convert it into GDP.
The researchers test the effects of this drug with human tumor cells grown in the laboratory and verify that those that have mutated Ras are clearly inhibited in their growth. These are encouraging results.
However, there is still a long way to go before this drug can be made available in hospitals or in pharmacies. It will be necessary to carry out studies with laboratory animals and patients to verify its effectiveness and absence of serious side effects. In any case, this discovery tells us that the application of knowledge about the molecular structure of oncoproteins and the application of chemical and pharmaceutical technologies may perhaps one day achieve the dream of curing some cancers by simply taking a pill quietly at home.
NEW WORK BY JORGE LABORDA.
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Chained circumstances. Ed. Lulu
Other works by Jorge Laborda
One Moon, one civilization. Why the Moon tells us that we are alone in the Universe
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