Cancer cell, kill yourself about the DNase!
A new method of personalized therapy causes cancer cells to kill themselves
Nanonews Network based on the materials of Wayne State University:
Researcher creates patented personalized therapy that causes cancer cells to kill themselves
A research doctor from the Wayne State University School of Medicine has developed a personalized method for treating a wide range of cancers. The treatment is based on a genetically modified enzyme, the natural version of which is present in the human body. A modified version of the enzyme is able to "trick" cancer cells and make them kill themselves.
The unique concept, patented by Wayne State University, has been successfully demonstrated on melanoma cells showing resistance to conventional treatments such as chemotherapy and radiation. Melanoma is an ideal model for testing a new therapy method, as it is considered the most aggressive form of human cancer due to many mechanisms that protect it from currently available treatments. Success in the treatment of melanoma suggests similar results in the treatment of other types of cancer.
The method developed by the Doctor of Medicine and Philosophy Karli Rosner (Karli Rosner) for the detection and destruction of cancer cells uses genetic constructs that contain a genetically modified enzyme that cleaves the DNA molecule – DNase1 (DNase1). The method is published online in the journal Cancer Gene Therapy (Engineering a waste management enzyme to overcome cancer resistance to apoptosis: adding DNase1 to the anti-cancer toolbox).
Associate professor and research director of the Department of Dermatology, Dr. Rosner modified the genetic code of the DNase, and changed its composition by removing one part of the code, introducing a mutation into another and adding an artificial fragment to it. Due to this, the modified DNA program is translated into a modified protein. Unlike the natural one, the modified protein is not removed from the cancer cell, successfully resists deactivation by cellular inhibitors and has access to the cell nucleus.
"If you think of the cell nucleus as a computer, and the DNA in the nucleus as software," explains Dr. Rosner, "then the modified, hacked DNA program corresponds to a computer virus. For a deeper understanding of this anti–cancer technology," he continues, "remember the plot of the film Independence Day. In this film, a computer virus is embedded in an enemy ship, neutralizing its defenses and making it vulnerable to external weapons. By introducing the modified genetic code of the DNase1 protein into the DNA of cancer cells alien to human health, we are doing something similar, but much better."
The cancer cell, unaware of the destructive potential of the altered code, translates it into a protein that can bypass its defense mechanisms and penetrate into the nucleus. In the nucleus, the protein damages DNA, splitting it into fragments, without the need to use external weapons, that is, other drugs. After DNA damage, cellular organelles disintegrate, and the cancer cell dies. Thus, Dr. Rosner's method "brings" cancer cells to "suicide", as it deceives them to produce a protein that causes their own death.
The beauty of this method lies in the fact that cancer cells that are specific targets are destroyed by a physiological mechanism – apoptosis, and the surrounding healthy cells remain intact. Such a method of destroying cancer cells does not leave any organic products capable of affecting the immune system, committing, in essence, an "ideal crime". This is important because many side effects of modern anti-cancer methods are associated with activation of the immune system. The fact that the method does not require the involvement of the patient's immune system is a huge advantage over other recently developed technologies, such as cancer vaccines. In the destruction of cancer cells, these technologies depend on the patient's immune system. Unfortunately, they are ineffective with a weakened immune system, which is typical for many cancer patients. In contrast, Dr. Rosner's method is able to treat patients with even the most severe damage to the immune system with the same success as patients with fully functional immunity.
The response of patients with the same type of cancer to identical treatment is different, since different patients usually have different biological characteristics of the same type of cancer. Therefore, medicine strives to develop such methods of treatment that could be adjusted taking into account the characteristics of the patient. The structure of Dr. Rosner's method has flexibility, as it contains separate parts that together form a genetic construct that can be compared to Lego. Each part of such a design can be replaced by one of several other parts that perform the same task, but differ slightly genetically. Several options available for each genetic part will allow the doctor to choose the final method for each patient based on the unique characteristics of his tumor. In this sense, the new technology is "truly personalized therapy," says Dr. Rosner. In order to determine the therapy option that destroys the patient's cancer cells with maximum efficiency, the doctor will first be able to test the effect of various genetic constructs on his cells obtained by biopsy.
Of particular importance is the potential of this method for the treatment of a wide variety of tumors, such as prostate, lung and breast cancer. Dr. Rosner compared his method to the platform of a military Tomahawk missile. The tomahawk is guided to the target by programming the missile homing device. A destructive genetic construct can also be oriented to a certain type of cancer by introducing a genetic fragment that specifically defines this particular cancer. The doctor will have several genetic homing devices at his disposal. The ability to focus treatment exclusively on cancer cells will reduce the side effects inherent in today's anti-cancer methods. In addition, the ability to focus treatment on different types of cancer will greatly increase the number of patients who can be helped by the new technology.
As Dr. Rosner foresees, one of the side effects of his method may be the lightening of a skin area to a level that he cannot accurately predict, but this is a compromise that a patient suffering from metastases and having a poor prognosis can make in exchange for a cure from cancer. To date, Dr. Rosner has demonstrated that the first generation of his "suicide gene therapy" kills 70 to 100 percent of cancer cells.
To further improve efficiency, he developed a second generation of designs. In the near future, Rosner plans to test the method on animal models – an intermediate stage before clinical trials.
Portal "Eternal youth" http://vechnayamolodost.ru02.03.2011