Genetic ensembles in oncology

7 facts about the work of genes in oncological diseases
and the use of targeted drugs

Anton Buzdin, Post-science1. Changing the work of genes in oncological diseases

The process of cell malignancy, that is, the transformation of cells from normal to cancerous, is accompanied by a very large-scale restructuring of the work of cell genes, the so-called transcriptome.

At the same time, the work of thousands of genes is changing. If a person has about 25,000 protein-coding genes in total, then with cancer, as a rule, the work of at least every tenth gene changes.

Among them there are genes whose function is to restrain tumor growth, that is, to restrain uncontrolled division, and there are genes whose function, on the contrary, is associated with the implementation of division. In a normal cell, a balance is maintained between cell death and division. The cancer cell is characterized by an imbalance of these basic principles, that is, division begins to clearly prevail over cell differentiation and cell death. The system of checks and balances that exists in a normal cell is violated. This is due to the fact that the genes that help the cell divide work more actively than they worked in a normal cell, and vice versa, the activity of the genes that controlled them and prevented them from working more actively than they normally should.

2. Intracellular signaling pathwaysThe root cause of this is genomic changes, mutations or so-called epigenetic changes.

At the same time, there is a massive restructuring of the genome. If you imagine a pile of three thousand genes that work differently, this in itself will not say anything. However, the work of all genes can be classified in such a way that genes can be considered not by themselves, but in the context of the biological processes for which they are responsible, so genes can be divided into ensembles — intracellular signaling pathways.

3. Analysis of the work of gene ensemblesEach signal path has some signal at the input and some action that it triggers at the output.

For example, at the input there may be a binding of a cell with a growth factor or hormone, and at the output there is a change, for example, in the work of a large number of genes. Genes can be decomposed into signaling pathways, analyzing the work of which, it is possible to imagine much more accurately what exactly is happening in the cell than when analyzing specific, individual, single genes.

Let's imagine a signal path in which there are about a hundred participants. Each of these participants can be changed in cancer, here the variability is very large, but at the output we get the same action. That is, changing the work of each of these hundreds of participants can lead to the same consequence. Thus, analyzing the work of gene ensembles seems to be a much more correct approach than analyzing each gene separately.

4. New methods for analyzing large amounts of dataThe science of bioinformatics, which has flourished in recent years and is formed at the junction of biology, physics, mathematics and computer science, allows us to solve a number of problems faced by researchers, classical biologists, namely: how to analyze huge amounts of data?

For example, the work of three thousand genes in three hundred tissue samples. Conventional methods of biology, of course, will not be able to cope with this.

Bioinformatics allows you to create algorithms for analyzing such large ensembles of genes in order to get valuable information about what exactly happened to the cell and, most importantly, what processes can be suppressed so that the cancer cell stops feeling comfortable. That is, knowing which regulatory pathways are activated more strongly than in normal cells, it is possible to choose such drugs that will selectively block this signaling pathway, which will significantly complicate the life of the cancer cell and help therapy.

5. Cancer therapyEach patient has an individual set of signaling pathways that are activated in his cells, and when it comes to personalized medicine, it should be understood that for each patient, you should choose your own course of therapy that will kill his cancer cells, and not the cells of some average patient, with a diameter of one meter and a weight of one kilogram, that is, non-existent in nature.

Thus, it is obvious that a detailed analysis of gene expression, coupled with bioinformatics methods, can give a real breakthrough in healthcare of the XXI century, which inspires and inspires optimism to researchers in the field of molecular oncology.

6. Effectiveness of targeted drugsIt is noteworthy that recently there have been more and more so-called targeted drugs, that is, drugs designed to suppress some specific gene products, but at the same time do not affect anything else.

Targeted drugs can, for example, block the passage of a signal through intracellular signaling pathways in a cancer cell. Such drugs can be selected for each of the signaling pathways specifically to block it if necessary. Recently, there has been a boom in such drugs, both among those that are undergoing clinical trials and among those that are entering the market. Now, for example, about a hundred targeted drugs for the treatment of cancer have entered the market, but several thousand drugs are already undergoing clinical trials. Of course, a number of these clinical trials will be unsuccessful, but it is obvious that the number of targeted drugs for cancer treatment will increase exponentially.

7. Side effects of targeted drugsAt the same time, there is one very big difficulty.

It lies in the fact that most of these drugs have their side effects, and the patient's life is often too short to try many different options on him. That is why it is very important to immediately prescribe such drugs to the patient that will help him. That is, from all the variety of drugs that already exist and will soon appear on the market, it is necessary to choose the ones suitable for a particular patient. It seems to me that this can be done most rationally with the help of methods of systemic molecular medicine, generously using methods of bioinformatics, a kind of molecular oncology of the future.

About the author:
Anton Buzdin – Doctor of Biological Sciences, Head of the group of genomic analysis of cell signaling Systems at the Institute of Bioorganic Chemistry. Academicians M. M. Shemyakin and Yu. A. Ovchinnikov of the Russian Academy of Sciences.

Portal "Eternal youth" http://vechnayamolodost.ru18.06.2014