RNAi screening used for the first time to study Ewing's
sarcoma
PHOENIX, Ariz. - Aug. 31, 2010- The first study of Ewing's sarcoma
that screened hundreds of genes based on how they affect cell
growth has identified two potential anti-cancer drug targets,
according to a scientific paper by the Translational Genomics
Research Institute (TGen) published this month in the journal
Molecular Cancer.
Ewing's sarcomas are rare, but aggressive cancer lesions that occur
most frequently in the bones of teenagers. They represent nearly 3
percent of all childhood cancers. Patients are treated with a
combination of surgery, radiation and chemotherapy. This cancer can
reoccur after surgical removal, and often spreads to the lungs,
other bones and bone marrow. Once it spreads, or metastasizes, only
1 in 5 patients survive more than 5 years.
These lesions harbor unique chromosomal abnormalities that give
rise to fusion genes that act as cancer-inducing proteins, or
oncoproteins.
TGen researchers used RNAi-based phenotypic, or loss-of-function
screening, a method of silencing hundreds of individual genes in a
high-throughput format, to analyze 572 kinases that are expressed
in human cells. Kinases are enzymes that modify other proteins.
Using this technique, the authors discovered two protein kinases
with important roles in the growth and survival of Ewing's sarcoma
cells. Cancer cells died when investigators stopped the normal
function of the two protein kinases called STK10 and TNK2.
"RNAi-based phenotypic profiling proved to be a powerful gene
target discovery strategy, leading to successful identification and
validation of STK10 and TNK2 as two novel potential therapeutic
targets for Ewing's sarcoma," said Dr. David Azorsa, a TGen Senior
Investigator and the paper's senior author.
This was the first study demonstrating the use of this kind of
phenotypic profiling to identify unique kinase targets for Ewing's
sarcoma, according to the paper.
By identifying kinases that regulate the growth of Ewing's sarcoma
cells, TGen investigators anticipate a rapid translation of their
discoveries into clinical drug trials and specific remedies for
individual patients, advancing the prospects of personalized
medicine.
"We undertook this study with the goal of identifying specific
kinases that can be targeted to modulate Ewing's sarcoma cell
growth and survival," said Dr. Shilpi Arora, a TGen Staff Scientist
and the paper's lead author. "In addition to the identification of
specific kinase targets, we were able to obtain a better
understanding of contextual vulnerabilities in Ewing's
sarcoma."
The Ewing's Research Foundation, founded by Reed Kavner, a Ewing's
sarcoma patient, and the V Foundation for Cancer Research, funded
this study.
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About TGen
The Translational Genomics Research Institute (TGen) is a Phoenix,
Arizona-based non-profit organization dedicated to conducting
groundbreaking research with life changing results. Research at
TGen is focused on helping patients with diseases such as cancer,
neurological disorders and diabetes. TGen is on the cutting edge of
translational research where investigators are able to unravel the
genetic components of common and complex diseases. Working with
collaborators in the scientific and medical communities, TGen
believes it can make a substantial contribution to the efficiency
and effectiveness of the translational process. TGen is affiliated
with the Van Andel Research Institute in Grand Rapids, Michigan.
For more information, visit: www.tgen.org.
Press Contact:
Steve Yozwiak
TGen Senior Science Writer
602-343-8704
[email protected]
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