This “chaos enzyme” may carry the key to stopping the spread of cancer

“A malignant tumor is the main cause of patients with three negative times for breast cancer in weakness,” said Dr. Vivic Mittal, Professor of Ford Isom Research for Heart Surgery at the Sanddra and Edward Mayer Center in Will Cornell. “Our study indicates a new therapeutic approach to prevent a malignant tumor before it begins and helps patients to overcome this deadly cancer.”

The results published on October 2 Cancer detectionHe challenges the popular idea that cancer treatments should enhance errors dividing the cells that already occur in cancer cells that exceed the point of collapse to urge cell death. When natural cells are divided, chromosomes – the “genetic beams” of the genes – are repeated – and are equal to the daughter’s cells. This process goes into many cancer cells, which leads to the instability of chromosomes: a lot of chromosomes or very few or mixed in multiple daughters cells.

“I find that the attempt to lead cancer cells across the edge with more chromosomes instability in relation to a little because if you do not reach the right level, this may lead to aggressive disease,” said Dr. Mittal. “Instead, the results we have found indicate that regime restoring the cell division by targeting EZH2 can prevent them from spreading.”

The first author, Dr. Shelli Yang Bay, started this work as a graduate student and is now a post -doctoral partner with Dr. Metal in Heart Surgery in Will Cornell Medicine. Dr. Samuel Bakhoum, who was at the Memorial Celed Cancer Cancer Center at the time, participated in the leadership of this study.

Connecting the science of creation and malignant tumor

About 5 % of the cells are likely to turn in the TNBC essential tumor, and these cells are characterized by unique features such as various metabolism, increased instability of chromosomes and variable creation science – adjustments to the DNA or associated proteins that do not directly change the genetic code.

Dr. Metal team found a suspicious adequacy that could lead to the spread of a malignant tumor in these special cancer cells: EZH2. This protein usually adjusts how to fill the DNA in the cells. But the cancers often kidnap EZH2 by increasing their production. In TNBC, this excessive production silences the main genes needed for chromosomes to separate properly during cell division and to rampant errors.

When analyzing data from breast cancer patients, Dr. Bay found that patients with higher levels of EZH2 also have cancer cells with chromosomal changes. This provided evidence for more laboratory experiences. With EZH2 discharge with Tazmetostat, which is an approved drug from the Food and Drug Administration (FDA) for the treatment of some cancer, low stability of chromosomes in cell lines, which genetically enhances EZH2 levels in cell division.

Moreover, EZH2 mouse models showed high chromosome instability in primary tumors an increase in lung tumor compared to tumors that lack EZH2, which confirms the existence of a direct link between EZH2 levels, chromosomes instability and malignant tumor. But how was the instability of EZH2 leadership?

Chromosomes chaos

The team discovered that EZH2 controls the Tankyrase 1 gene, which usually guarantees the chromosome separation machines operating properly while dividing the cells. This leads to a chain reaction – a decrease in Tankyrase 1 causes another protein called excessive accumulation. This demands the central graphics of the cell – the structures that separate the chromosomes – to beating without their account, which leads to defective divisions into three cells or more.

The team showed that inhibiting the restored EZH2 balance, which greatly reduces a malignant tumor in pre -clinical models. “For the first time, we tied EZH2, a genetic organizer, with chromosomes instability in a mechanical way,” said Dr. Bay.

EZH2 inhibitors may be the first medications that can suppress chromosomes directly. “This study provides a promising new approach to the treatment of negative triple breast cancer by targeting the radical cause of the bumps.” Said Dr. Magdalina Plasilova, associate professor of clinical surgery (suspended in the center). “I closely see the devastating effect of the inheritance on patients, and this provides hope for improving results and survival rates.”

While Tazmetostat can be reused as TNBC treatment, other drugs may have similar or better effects. “Our discovery opens the door for clinical trials of the EZH2 inhibitors in high -risk breast cancer and possibly other types of cancer that are also characterized by the instability of chromosomes, such as lung cancer,” said Dr. Mittal, a member of the Institute of Define Medicine in England. Currently, he plans to cooperate to conduct safety tests in a clinical trial.