Two main features distinguish the stubborn cancer cell: it grows without control, and does not obey the biological suicide instruction; Cracking these features may lead to a breakthrough in the development of drugs for the disease
By: Marit Selvin
The fight against cancer is difficult and frustrating. The reason for this lies in the two main unique properties of cancer cells. One: the cancer cell multiplies rapidly, in an uncontrolled manner. The second: a cancer cell does not obey suicide orders.
Normal cells that are under stress activate a "suicide program" inherent in their genetic material. The software is activated when cells receive instructions to divide continuously, or when changes occur in the DNA that damage the basic functions of the cell. The cancer cell, however, does not kill itself. As a result of mutations that occurred in him, he knows how to activate mechanisms that prevent the activation of the suicide software.
These two unique characteristics of the cancer cell are the result of DNA mutations, which cause the creation of abnormal proteins that disrupt the normal life course of the cell. These proteins serve as good targets for the development of drugs based on substances that inhibit their activity. These drugs, unlike the drugs available today, will selectively damage the cancer cells only and prevent the severe side effects associated with chemotherapy treatments.
The drug "Gleevec", which came on the market a year ago, marked a revolution in cancer treatment. This is the first time they have succeeded in producing a drug that intervenes in the chain of biochemical processes that distinguish the cancer cell from the normal cell, and therefore only affects the malignant cells. The development of the drug is based on an idea developed by the winner of the Israel Prize, Prof. Alexander Levitsky from the Institute of Life Sciences at the Hebrew University.
Gleevec works in a malignant blood disease called chronic myeloid leukemia, and its development resulted from the understanding that in this disease a single mutation turns the blood cell from normal to cancerous. Gleevec is a molecule that enables the death of the cancer cell as a result of inhibition of biological action. The drug significantly extends the life expectancy of patients with chronic myeloid leukemia.
These days Levitsky is trying another strategy. "We want to force the cancer cells to commit suicide," he explains. "For this purpose, we mobilize a biological mechanism that exists in each and every cell. This is a special protein called PKR, which is activated when the cell is infected with a virus. The protein activates the suicide program in the cell and causes the cell to commit suicide altruistically when a virus is inside it, thus preventing the spread of the virus to other cells."
The new strategy was developed as part of Alexei Shir's doctoral thesis, supervised by Levitsky. Shir decided to take advantage of the unique feature of the PKR protein and activate it only in cancer cells. In order to activate the suicide program in the cancer cells only, Shir searched for unique components in their genetic material."
The results of the study confirmed the researchers' working assumption: only in the cancer cells was the suicide program activated, while the normal cells remained "indifferent" to the new sequence, this is because they did not have the complementary sequence that characterizes the cancer cells. The cancerous tumors in the mice shrank significantly - more than 75%. The research, which will appear in the September issue of the Biotechnology journal "Nature", was allowed for early publication on the Internet yesterday.
"We proved that it is possible to 'cheat' the cancer cells and make them commit suicide," says Levitsky. "The fact that our strategy works will make it possible to apply it in those cases where the molecular essence of the mutation is known, and it is possible to develop RNA molecules that will cause the cancer cells to commit suicide. The application in humans still requires long-term research, but we hope that with the help of the strategy we have developed, it will be possible to develop drugs that will act exclusively on the cancer cells."
