Scientists Uncover the Secret of Brain Cancer’s 'Immortality Switch'

Researchers have used the gene-editing tool CRISPR to unlock the secret of brain cancer's deadly dividing strength.

Researchers have discovered a way to slow or halt cancer cells from spreading. Many types of cancers cells are able to divide indefinitely, by turning on an 'immortality switch'. Now, scientists from the University of California, San Francisco, have discovered a way to turn this switch off and thus slow down cancer cell growth.

The research covers more than 50 types of cancer, including the type that caused the death of Senator John McCain. A study led by Joseph Costello, a professor of neurosurgery and a neuro-oncology expert examined glioblastoma brain cancer cells that had been removed from cancer patients.

GABP protein responsible for aggressive cell divison

The research team discovered that the key to enabling cancer cells to activate the so-called 'immortality switch' was a tiny segment of a common protein called GABP. When this protein was removed, the cancer cells stopped multiplying and behaved like regular cells. The experiment was conducted on both cells in lab dishes and on cells transplanted into mice.

Most cells can only divide a certain amount of time before they die, however, cancer cells can continue to divide unchecked. The exception in regular cells is stem cells.

Regular cells have limited division ability

Stem cells divide to replenish other cells that are dying like skin and blood cells. Cell life is set by structures called telomeres which sit atop the end of chromosomes.

With each cell division, the telomeres get shorter until they cannot protect the integrity of the chromosomes and the cell division stops. Stem cells differ in this way by using an enzyme called telomerase that rebuilds the telomere.

Cancer cells do something similar by exploiting mutations in a gene called TERT, an acronym for telomerase reverse transcriptase. When cancer cells turn this gene on, they can divide indefinitely just like stem cells.

Previous TERT blockers too toxic

Scientists have discovered that 90 percent of tumors have mutations that allow the growths to turn on TERT expression and produce telomerase. Drugs that block telomerase have proven to be too toxic for patients, because the medicines affect the patients' stem cells too, limiting their ability to make new blood cells.

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The new research is focused on glioblastoma, the most aggressive form of brain cancer. The research team have discovered a method of treating the cancer that targets only the cancer cells' immortality switch, and avoids damaging stem cells.

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When the team found that cancer cells were using part of the GABP protein to turn on the infinity switch they knew they couldn’t just inhibit the whole protein as it had a large role in other major tasks. Instead, they experimented with removing just the GABP-β1L element, using the gene-editing tool CRISPR.

Results so far show incredible results. The GABP protein without β1L had a detrimental effect on cancer cells but no effect on other cells. "These findings suggest that the beta 1 subunit is a promising new drug target for aggressive glioblastoma and potentially the many other cancers with TERT promoter mutations," Costello said in a press statement.

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The research is published in the journal Cancer Cell.

Via: UCSF

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