Scientists ID gene responsible for deadly glioblastoma

Date:
July 14, 2020
Source:
University of Virginia Health System
Summary:
The discovery of the oncogene responsible for glioblastoma could
be the brain cancer's Achilles' heel, one researcher says.



FULL STORY ========================================================================== Scientists have identified an oncogene (a cancer-causing gene) responsible
for glioblastoma, the deadliest brain tumor. The discovery offers a
promising new treatment target for a cancer that is always fatal.


==========================================================================
The researchers say the oncogene is essential to the survival of
the cancer cells. Without it, the cancer cells die. Scientists have
already developed many targeted therapies for other cancers with a
similar "oncogene addiction." "Glioblastoma is one of the most deadly
cancers. Unfortunately, there is no effective treatment option for
the disease. The current standard option, radiation plus temozolomide,
which displayed a 2.5-month better survival rate, was hailed as a great success. Clearly, better understanding and new therapeutic targets
are urgently needed," said researcher Hui Li, PhD, of the University of Virginia School of Medicine and the UVA Cancer Center. "The novel oncogene
we discovered promises to be an Achilles' heel of glioblastoma, with its specific targeting potentially an effective approach for the treatment of
the disease." Targeting Glioblastoma Oncogenes are naturally occurring
genes that spiral out of control and cause cancer. The oncogene Li and his colleagues identified, AVIL, normally helps cells maintain their size and shape. But the gene can be shifted into overdrive by a variety of factors,
the researchers found. This causes cancer cells to form and spread.

Blocking the gene's activity completed destroyed glioblastoma cells in
lab mice but had no effect on healthy cells. This suggests targeting
the gene could be an effective treatment option.



========================================================================== "AVIL is overexpressed in 100% of glioblastoma cells and clinical samples,
and is expressed at even higher level in so called glioblastoma stem
cells, but hardly expressed in normal cells and tissues," said Li, of
UVA's Department of Pathology. "Silencing the gene wiped out glioblastoma
cells in culture and prevented animal xenografts, while having no effect
on normal control cells.

Clinically, high AVIL expression correlates with worse patient
outcome. These findings and classic transformation assays proved AVIL
being a bona fide oncogene." Identifying Oncogenes Identifying an
oncogene, as Li and his colleagues have done, is an important step toward developing a treatment. But identifying oncogenes is very difficult. The environment inside cells is so complex that it's hard to determine cause-and-effect.

Li and his team weren't even working on glioblastoma when they first
caught the scent that led to the discovery. Instead, they were studying
a rare childhood cancer called rhabdomyosarcoma. (Childhood cancers
typically are easier to understand and involve fewer mutations than
adult cancers.) During their research, the scientists discovered
an abnormality in the AVIL gene. That prompted them to examine adult
cancers to see if the gene could be contributing there. And it was. The researchers concluded the gene plays a "critical role" in glioblastoma,
they report in a new scientific paper outlining their findings.

Li and his team believe their approach can be used to discover other
oncogenes -- hopefully leading to new treatments for a variety of cancers.

"In this day and age, many people thought that all the significant
oncogenes have been discovered, Here we uncovered a novel powerful
oncogene, and elucidated its signaling pathways, all starting from
studying a structure variant in a pediatric cancer. In the past, numerous significant discoveries in cancer also stemmed from studying pediatric
tumors" Li said. "We believe this is a strategy can be applied to find
novel players in other adult cancers."

========================================================================== Story Source: Materials provided by
University_of_Virginia_Health_System. Note: Content may be edited for
style and length.


========================================================================== Journal Reference:
1. Zhongqiu Xie, Pawel Ł. Janczyk, Ying Zhang, Aiqun Liu,
Xinrui Shi,
Sandeep Singh, Loryn Facemire, Kristopher Kubow, Zi Li, Yuemeng
Jia, Dorothy Schafer, James W. Mandell, Roger Abounader,
Hui Li. A cytoskeleton regulator AVIL drives tumorigenesis
in glioblastoma. Nature Communications, 2020; 11 (1) DOI:
10.1038/s41467-020-17279-1 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/07/200714102101.htm

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