For each tumor – personal preparations
How to choose a cure for cancer?STRF.ru
Oncological diseases are the second most common cause of death in the world.
Success in cancer therapy depends, first of all, on timely diagnosis and the development of an optimal treatment regimen. But currently, standard sets of medications are used to fight malignant tumors – so it is not surprising that they are not always effective.
Perhaps the most important result of modern research in the field of oncology was the understanding that there can be no single panacea for cancer. Almost every case of cancer is individual, since the development of a tumor involves the sequential accumulation of damage in a large number of genes. Therefore, knowledge of the features of molecular mechanisms in the cells of a particular tumor can help doctors, which will allow them to apply the optimal treatment regimen. But how to understand which medicine should be used in a particular case?
A team of Moscow scientists from the Russian State Medical University and the V. A. Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences (O.O. Favorova, V.S. Prasolov, M. Chumakov, P.M. Rubtsov, etc.) is developing a method for determining the functional profile (a set of "working" genes) of a specific tumor, which in the future will allow personalized therapy of patients cancer patients.
During the development of a cancerous tumor, gene damage in its cells affects, among other things, the work of the so-called signaling pathways that transmit molecular signals from outside into the cancer cell, forcing it to divide uncontrollably. At the same time, there is a change in the activity of transcription factors – proteins, like conductors? controlling the work of genes. This activity can be measured using artificially created genetic reporter constructs injected directly into the tumor cell (they are called reporter because they allow you to directly monitor the work of certain genes). And the use of a combination of reporter genes will simultaneously determine the state of several signaling pathways to obtain a functional profile of a single tumor. Moreover, it will be possible to introduce reporter constructs directly into tumors with high efficiency, and then analyze the functional state of cancer cells in the biopsy material.
As a basis for such genetic constructs, scientists used a lentiviral vector – a system for delivering the necessary genes into the cell. Currently, reporter constructs have been obtained that respond to changes in the activity of transcription factors p53, NFkB, HIF-1a and HSF. The fact is that the change in the activity of these transcription factors is characteristic of a wide range of tumors, and the success of the chosen treatment method may depend on their level. To test these structures in vitro, they were introduced into cancer cell cultures that differ in the functional state of the corresponding signaling pathways. In addition, by treating cells with a number of chemotherapeutic drugs that affect the activity of transcription factors, it was possible to register changes in the expression of so-called reporter genes, including the green fluorescent protein gene (GFP).
The principle of operation of the developed scheme is well demonstrated by the work of reporter constructs that measure the activity of the p53 suppressor gene, which "monitors" the integrity of the DNA molecule in the cell nucleus. In case of serious DNA damage, the protein – the product of the p53 gene – triggers the process of programmed death (apoptosis) in cells. The activity of this gene is absent as a result of mutations in half of human tumors. In cells with a violation of the p53 structure, the expression of the reporter gene does not occur, while when injected into normal skin fibroblasts, the expression of the reporter can be caused by treatment with anticancer chemotherapeutic drugs (5-fluorouracil or camptothecin). It is important to note that the change in expression is quantifiable and reproducible in independent experiments. At the same time, in the same cells, p53-specific treatments do not cause a noticeable change in the activity of the reporter for the transcription factor NFkB (which, on the contrary, prevents the triggering of the mechanism of apoptosis). A further stage of the work of Moscow scientists will be the development of conditions for simultaneous detection of the activity of two or more transcription factors using several reporter genes.
Portal "Eternal youth" http://vechnayamolodost.ru10.11.2009