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Cellular Kill Code Discovery May Help Extinguish Cancers

Cancer is one of the most devastating diseases that affect the human being since it implies a great physical and mental deterioration of the patient and their relatives. In recent years, many investigations have been carried out for the treatment and prevention of cancer, one of the most interesting recent findings is the evaluation of the role played by the immune system in the destruction of cancer cells.

Researchers at Northwestern University have discovered an effective way to activate the genetic mechanisms that cause the death of cancer cells. The application of this knowledge can lead to a therapy in which cancer cells kill themselves, making the development of mechanisms of resistance by malignant cells impossible.

Cancer begins due to an imbalance in the growth and cell  multiplication; this causes the cells of a certain tissue to multiply uncontrollably leading to the formation of tumors. Cancer cells also have the ability to spread lymphatically or vascularly and invade other tissues (metastasis). The formation of cancer cells activates the immune system which, through various molecular and cellular mechanisms, eliminates malignant cells. However, the immune system does not always respond adequately because cancer cells develop defense mechanisms that prevent their destruction by the immune system.

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The researchers discovered that throughout the human genome there are multiple sequences of genes that can turn into small molecules called small interfering RNAs (siRNAs). These molecules have the ability to interact with the genetic material of the target cells by suppressing DNA replication causing the death of the cell. The research team developed siRNA molecules that act specifically on three genes of cancer cells, inducing the death of these.

Because these molecules act on three different survival genes simultaneously, they manage to trigger several cell death pathways, making it impossible for cancer cells to develop mechanisms of resistance to treatment. The researchers call the mechanism of cell destruction Death Induced by Survival gene Elimination (DISE).

A bit disconcerting is the fact that the DISE mechanism can be applied to virtually any cell. However, the research team ensures that the siRNA molecules act preferentially on the cancer cells. The researchers tested the treatment in mice with ovarian cancer and found that tumor growth was significantly reduced, with no toxic side effects and no signs that cancer developed resistance to treatment.

New research by Dr. Marcus Peter and his team at Northwestern determined that a series of six nucleotides called 6mer is widely involved in the mechanism by which siRNA molecules kill cancer cells. It has been proven that there are more than 4,096 possible combinations of nucleotides in the 6mers, the researchers were responsible for testing each of these combinations to determine which of these is more toxic for cancer cells. The most toxic 6mer combination was dubbed G-rich, which is used by the micro RNA that the body releases naturally to fight cancer.

The findings of this research are very important for the development of more effective treatments for cancer. However, we are still far from applying these therapeutic measures in humans, commented Dr. Marcus Peter.

For now, the future plan of this research team is to design artificial microRNAs that are even more effective than natural molecules.

Perhaps the most interesting aspect of this research is the way in which it takes advantage of the body's natural mechanisms to fight cancer cells. It is estimated that this siRNA mechanism that kills cancer emerged more than 800 million years ago, and now humans have discovered, with luck and a lot of work in the coming years this mechanism can be improved and applied with great efficiency in the treatment of cancer.

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