18 March 2014

Liquid biopsy

New blood test for cancer

Vladimir Fradkin, Deutsche WelleIf a cancer is suspected, doctors will certainly take a tissue sample for microscopic analysis of cells.

Although in most cases this procedure, called a biopsy, is performed minimally invasive today, that is, it does not require serious surgery, it nevertheless involves some risk, is accompanied by rather unpleasant sensations, and sometimes does not give the desired result. Meanwhile, a biopsy is not only a mandatory method of confirming the diagnosis in case of suspected cancer: the nature of further steps in tumor therapy also depends on its results.

Tempting, but difficult to implement ideaNow a group of American researchers has developed a new diagnostic method, called liquid biopsy.

Chetan Bettegowda, a neurosurgeon at Johns Hopkins University School of Medicine in Baltimore, Maryland, says: "We understood that we needed to look for more effective ways to detect tumors of various types in the early stages of development, when they are relatively easy to treat. One of these ways is to search for tumor DNA in a blood sample."

In order for a blood test to reliably detect a cancer that has barely originated somewhere in the human body - of course, this sounds very tempting. The only trouble is that it is very difficult to put this idea into practice: there is a huge amount of DNA in the blood, starting with the genetic material of the blood cells themselves and ending with DNA fragments from various dead cells of the body. The proportion of DNA of tumor cells, especially at an early stage of the disease, is no more than one hundredth of a percent. In addition, cancer cells are degenerated normal cells of the same organism, and therefore their genetic material is very much identical to the DNA of healthy tissues.

The concept works. But not alwaysNevertheless, there are certain differences.

It was on them that the Baltimore doctors made a bet. Chitan Bettegauda explains: "We are looking for quite specific mutations typical of cancer cells. These are the mutations that give tumor cells the ability to divide uncontrollably, they do not occur in healthy cells."

Using a polymerase chain reaction, the researchers amplified in a blood sample those fragments of chromosomal DNA that contain genes involved in the formation of cancerous tumors. Typically, these genes encode proteins that regulate cell growth, differentiation, and division. The presence of certain mutations can turn these genes into oncogenes, the products of which stimulate the formation of malignant neoplasms. Experiments on several hundred cancer patients have confirmed that the concept of liquid biopsy proposed by Baltimore doctors really works.

But, unfortunately, not always. Firstly, it is not suitable for the diagnosis of brain tumors: apparently, the necessary DNA fragments from cancer cells are not able to overcome the blood-brain barrier. Secondly, the method does not allow detecting malignant tumors in the early stages of the disease, and this is exactly the goal that the developers originally set for themselves.

Genetic signs of resistanceHowever, Chitan Bettegauda is confident that the sensitivity of the method will be significantly increased.

But this, he admits, will take more than one year. Meanwhile, liquid biopsy can find application in clinical practice right now, says the scientist: "We know that in oncology relapses are often associated with the development of resistance of cancer cells to drugs used in therapy. In patients suffering from colon carcinoma, we were able to observe how mutations appear in the DNA of tumor cells, as a result of which these cells become immune to chemotherapy. Therefore, it seems reasonable to us to regularly monitor tumor DNA in the blood of patients. This will allow the doctor to switch to alternative medications when the patient shows the first signs of developing resistance and thereby increase the effectiveness of therapy."

Moreover, liquid biopsy even has important advantages over traditional biopsy. After all, a classical biopsy involves the sampling and examination of a very small fragment of tumor tissue, and signs of resistance development may not be detected in it. DNA fragments from various tumor sites are present in the blood, so their analysis will give more reliable and reliable results. A liquid biopsy will also help to find out whether this tumor responds at all to the therapy prescribed by the doctor. Such tests in patients with already diagnosed oncological diseases may become routine in the next year or two. As for the early diagnosis of cancer, that is, the goal that, in fact, was originally set by Chitan Bettegauda, its achievement seems to be a matter of a much more distant future.

Article by Bettegowda et al. Detection of Circulating Tumor DNA in Early- and Late-Stage Human Malignancies is published in the journal Science Translational Medicine;
On the Johns Hopkins Medicine website, you can read the press release of New Hope for Early Cancer Screen - VM.

Portal "Eternal youth" http://vechnayamolodost.ru18.03.2014

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