An antipsychotic remedy will help to avoid relapses of leukemia
A remedy against cancer stem cells has been found to prevent relapse
Roman Ivanov, Computer
Widely used to treat the symptoms of schizophrenia, the remedy, as it turned out, helps extremely effectively in the fight against cancer. Laboratory studies have shown that the drug absolutely kills the cells that give rise to leukemia, without affecting healthy tissues. In other words, an unexpected ally is able to open up to oncologists a long-sought way to completely destroy even traces of leukemia, without the possibility of a relapse in the future.
Acute myeloid leukemia is a malignant tumor of the myeloid blood germ, in which altered white blood cells (leukocytes) multiply rapidly. Accumulating in the bone marrow, they inhibit the growth of normal blood cells. – VM.
Despite the fact that existing methods, including surgery, chemotherapy and radiation, can rid the patient of a tumor or leukemic cells, the disease most often returns after months, at best years. One of the main culprits of the trouble may be cancer stem cells, giving rise to a new disease. These cells show the highest resistance to chemo- and radiotherapy and remain in the patient's body as a silent threat, waiting for their time, which will surely come. Many oncologists believe, not without reason, that the optimal approach is a combination of traditional anticancer drugs and specialized agents aimed exclusively at cancer stem cells. But, since the latter exist in very small quantities (which, of course, on the one hand, is good) and are almost not amenable to cultivation in laboratory conditions, only a small number of such drugs have been proposed, and none of them has yet been approved for clinical use.
A group of Canadian scientists has found a new way that allows testing potential candidates for the title of "killers" of cancer stem cells. They suggested using embryonic pluripotent stem cells or reprogrammed adult cells that are capable of developing into various types of tissues. I must say that pluripotent stem cells are similar to cancer cells even in external manifestations: they continue to divide, but at the same time they do not develop (differentiate) into any highly specialized cells.
In the current study, scientists led by Mika Batia from McMaster University (Canada) decided to find out whether any chemical, after interacting with pluripotent stem cells, can differentiate (age) them into normal cells so that they stop dividing abnormally and switch to a normal cycle of life, at the end of which is natural death. The researchers felt that such an approach would be a much less toxic way of getting rid of scattered cancer stem cells than using a powerful drug capable of killing such cells directly (and, of course, not only them, but everything that gets in the way).
Extensive screening of hundreds of compounds, including drugs already approved for use, yielded several drugs that do exactly what scientists wanted: chemicals forced pluripotent cancer-like stem cells to differentiate (that is, at least begin to live using normal cellular mechanisms) without damaging the healthy stem cells needed by the body.
Screening scheme from an article in Cell – VM
One of the most effective drugs turned out to be thioridazine, a neuroleptic or antipsychotic agent used to treat symptoms of schizophrenia. When tested on real cancer stem cells taken from patients, it turned out that this substance blocks the growth of stem cells of acute myeloid leukemia, and then completely reduces the number of such cells to zero, which was confirmed in experiments on mice. Moreover, normal blood stem cells remained absolutely untouched.
On the right: cancer-like stem cells after treatment with thioridazine are almost completely destroyed.
On the left is a control sample (E. Sachlos micrograph)
The standard chemotherapeutic agent against acute myeloid leukemia in combination with thioridazine turned out to be 55 (!) times more effective in combating this most dangerous type of cancer in the laboratory, as follows from the work report published in the journal Cell (Sachlos et al., Identification of Drugs Including a Dopamine Receptor Antagonist that Selectively Target Cancer Stem Cells). Currently, 15 patients whose leukemia has already acquired resistance to standard chemotherapy have agreed to participate in clinical trials of combination therapy with thioridazine (everything is so simple only because both medicinal components have long been approved for use).
The study also revealed one surprising fact that was not known. Thioridazine, in its main specialty designed to block receptors that are designed to interact with the neurotransmitter dopamine, obviously also works on leukemia stem cells, blocking the same receptor. No one noticed that stem cancer cells possess dopamine receptors, which are usually associated with the nervous signaling system and are mainly located only in the brain. And Mr. Batia's group found these receptors in breast cancer stem cells as well. (Isn't this receptor the selective center whose interaction with thioridazine causes cellular differentiation that does not affect normal stem cells deprived of this particular receptor? In this case, everything becomes clear and understandable. But how was it necessary to guess?! It's like winning blindfolded cards.) This discovery can be used, for example, as a test procedure: by measuring the number of dopamine receptors in blood or tissue samples, you can detect cancer or build a possible prognosis for the patient.
Why do cancer stem cells need dopamine receptors? In the human head, dopamine is the main regulator of the main brain functions (rational – the search for food, social and emotional) responsible for the survival of the species. Moreover, it is the dopamine system that "oversees" the pleasure centers.
If anyone else doubts that cancer is a "different" form of life, re-read this paragraph.
Prepared based on the materials of ScienceNOW: Psychiatric Drug May Kill Cancer Stem Cells.
Portal "Eternal youth" http://vechnayamolodost.ru25.05.2012