Aging gene may make brain cancer chemo-proof for some, Israeli study shows

Finding solves the mystery of why older people often fare worse in treatment for glioblastoma, and opens new treatment target, say Ben Gurion University scientists

Nathan Jeffay is The Times of Israel's health and science correspondent

Chemotherapy is administered to a cancer patient. (AP Photo/Gerry Broome)
Chemotherapy is administered to a cancer patient. (AP Photo/Gerry Broome)

Israeli scientists are claiming new insight into why brain cancer often dodges chemotherapy in elderly patients — and say it could pave the way for a fix.

Elderly people who contract glioblastoma, a fast-growing and aggressive brain tumor, have a lower chance of responding well to chemotherapy than younger people. But researchers have struggled to understand why this is the case, when with most cancers the rates of response to aggressive chemotherapy are similar in patients young and old.

For years, brain scientists at Ben Gurion University have been studying a gene called TP73-AS1. They found in 2018 that active TP73-AS1 makes cells more resistant against chemotherapy.

The gene is disproportionately active in people with glioblastoma, and now the researchers say they understand why. They have heightened levels of a protein called YY1, which activates the TP73-AS1 genes.

These very same elevations in levels — for both YY1 and TP73-AS1 — are detected among elderly people, leading the Ben Gurion researchers to suggest that the protein and the gene contribute to the aging process and to causing vicious glioblastoma.

Illustration of brain cancer (wildpixel via iStick by Getty Images)

“This is important research because it suggests a connection, on a gene and protein level, between aging and brain cancer,” Prof. Dr. Barak Rotblat told The Times of Israel.

The fact that elderly glioblastoma patients have both their age and their cancer elevating their YY1 and TP73-AS1 levels could explain their relatively poor response to chemotherapy, he said.

Dr. Barak Rotblat (Dani Machlis/Ben Gurion University)

His team’s findings have just been published in the peer-reviewed journal Aging. Rotblat said that they will allow cancer researchers to deepen their understanding of connections between aging and the disease.

“Now, we are excited by the prospect that by studying TP73-AS1 and the molecular pathways it interacts with, we can learn about cancer and aging in the brain,” he said.

He added: “We can conduct further testing to examine the hypothesis that the gene and protein we are researching cause older people to suffer worse from glioblastoma. If this is right, we can start looking for cures and therapies that interfere with the production of TP73-AS1 and help people of all ages who have this cancer.”

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