UCSD. US: Researchers at the San Diego Supercomputer Center (SDSC), Moores
Cancer Center, and Department of Neurosciences at the University of
California, San Diego, have shown for the first time a pyramid
hierarchical network of “coherent gene modules” that regulate
glioblastoma genes, involved in a highly aggressive form of brain
cancer.
By identifying the most important gene modules responsible for cancer
growth and proliferation, the study informs a strategy that could
elucidate these modules at the top levels of their network, and in turn
be used to identify new drug therapies. The paper appears in the U.K. journal Molecular BioSystems, published by the Royal Society of Chemistry.
Glioblastoma
(GBM) is highly resistance to treatment and rapidly lethal. To date,
therapeutic targeting of individual molecules has proven unsuccessful in
treating GBM due to complex interactions of genetic pathways, signaling
networks, and cellular levels that are a hallmark of the cancer and
allow it to proliferate.
“Considering the complex interplay of mediators involved, it is clear
that examining individual signaling molecules or even pathways may not
give information accurately representing the underlying molecular
abnormalities,” said lead author Igor F. Tsigelny, a research scientist
with SDSC as well as the UC San Diego Moores Cancer Center and the
Department of Neurosciences.
Because of the number of connections involved, researchers relied on
the BiologicalNetworks server that used SDSC’s data-intensive Gordon
supercomputer. The test runs of this server queries on Gordon showed up
to a 200x application speed improvement. Of particular interest in the
study was elucidation of transcription regulators (TRs) and
transcription factors (TFs) that actually regulate the coherent gene
groups and the drug targeting that can be applied to these controlling
TRs and TFs.
“Our approach of identifying major multi-level hierarchical networks
and coherent gene modules within networks improves our understanding for
clinical translation,” said Tsigelny.
“This innovative network analysis identified several central nodes in
signaling networks in glioblastoma that could help us design
personalized clinical trials using available and new drugs in
development,” said Santosh Kesari, Director of Neuro-Oncology and a
professor of neurosciences at the Moores Cancer Center.
In addition to SDSC’s Tsigelny, researchers involved in the study
include Valentina L. Kouznetsova from SDSC; and Penfgei Jiang, and
Sandeep C. Pingle from the Moores Cancer