NEW YORK, NY--(Marketwire - December 29, 2009) - Therasis Co-Founder, Andrea Califano, Ph.D.,
and Wei Keat Lim, Ph.D., Head of Computational Systems Biology at Therasis,
along with a team of scientists at Columbia University, have reported in
the journal Nature the identification of two genes that, when
simultaneously activated, cause the most lethal form of glioblastoma, an
aggressive brain tumor. The findings were first published in an advanced
online edition of Nature on December 23, 2009,
http://www.nature.com/journal/vaop/ncurrent/pdf/nature08712.pdf.
The genes were identified by reverse-engineering a map of the complex
molecular interactions that occur within the actual tumor cells, also known
as a cellular network, using advanced cancer systems biology algorithms.
These computational methods and algorithms were developed in the laboratory
of Dr. Califano, who is also the Director of the Joint Centers for Systems
Biology and Associate Director of the Herbert Irving Comprehensive Cancer
Center at Columbia University Medical Center.
The team used one of the algorithms (ARACNe) to reconstruct the cellular
network that controls the behavior of these tumors. Then, a second
algorithm (MARINa) was used to identify the master regulators of the worst
prognosis in glioblastoma from this network. This analysis pinpointed two
genes, with no known prior association with brain cancer, as playing a key,
synergistic role in determining the most aggressive properties of
glioblastoma, including invasion of normal surrounding tissue and
angiogenesis. ARACNe and several other algorithms are exclusively licensed
to Therasis from Columbia University. Together, they form the
computational foundation of the company's robust drug discovery platform,
known as the Therasis Filter™.
The computational findings were confirmed by a follow-up validation study,
in which the expression of these genes was found to be strongly correlated
with increased mortality. Furthermore, the tumor network and genes'
functions were confirmed both in cell lines and in mouse models. Expression
of the two genes in neural stem cells caused them to display all the
hallmarks of the most aggressive glioblastoma. Conversely, silencing these
genes in aggressive human glioma cells, which are normally highly
tumorigenic when transplanted in mice, completely blocked their ability to
form tumors.
"This study validates the potential of the Therasis Filter™ to transform
oncology drug discovery and development by enabling a comprehensive
understanding of the inner regulatory interactions in actual tumor cells to
guide target identification," commented Dr. Califano. "These findings of
two new synergistic glioblastoma targets support our technology platform
and will guide new approaches to combination therapy and associated
diagnosis through targets and biomarkers that are causally, rather than
statistically, associated with the tumors."
Dr. Stefan Catsicas, Chairman of the Tilocor Group, whose Tilocor Life
Science arm has invested $12M into Therasis' Series A financing, added,
"This study illustrates that scientific excellence is necessary to develop
innovative treatments. The combined expertise of the founders and of the
management of Therasis should allow the company to translate this
excellence into clinical breakthroughs."
Rather than identifying therapies based solely on cytotoxicity, or ability
to kill cancer cells, the Therasis Filter™ enables a more informed
approach to drug development by determining key molecular targets and
uncovering synergistic interactions within a cellular network. The
subsequent reverse-mapping of the effects of a single agent or combination
on these cellular activities affords a better understanding of the mode of
action and specific toxicity of new treatments, as well as biomarkers of
activity.
Therasis was recently founded by Drs. Riccardo Dalla Favera, Owen O'Connor,
and Andrea Califano, leaders in basic, translational, and clinical oncology
research. The company is developing an internal pipeline of oncology drug
candidates and forming drug discovery partnerships with other
pharmaceutical and biotechnology companies.
About the Therasis Filter™
The Therasis Filter™ enables the identification of disease-specific
alterations in the networks of molecular interactions that regulate
cellular processes, allowing the rapid identification of new chemical
entities and synergistic combinations that target these alterations.
Beginning with high throughput screening of compound libraries, the
Therasis Filter™ first collects a large number of molecular profiles of
chemically-perturbed cells. These profiles are used to reconstruct accurate
maps of molecular interactions, also known as "interactomes." The latter
are experimentally validated and analyzed to identify disease-specific
alterations in tumor-derived tissues, compounds targeting these alterations
and biomarkers complementing clinical development. Interactomes are also
effective in characterizing drug mechanisms of action, supporting both drug
rescuing and drug repositioning efforts.
About Therasis
Therasis, Inc. is a new drug discovery company developing oncology
therapeutics for use as single agents or in combination therapy. The
Company's proprietary technology, the Therasis Filter™, represents a
paradigm shift in the ability to discover therapeutic targets, their
chemical inhibitors and associated biomarkers. This platform integrates
world-class expertise in high throughput screening, systems biology, cancer
genetics and clinical research. Therasis plans to leverage its discovery
engine to identify new chemical entities for internal development and to
forge collaborations with pharmaceutical and biotechnology companies on
drug repositioning.
Therasis' technology platform was developed at Columbia University by
internationally recognized thought leaders in cancer genetics, cancer
systems biology and cancer therapeutic development. The Company is funded
by Tilocor Life Science. Learn more at www.therasis.com.
About Tilocor
Tilocor has established a small group of innovation-driven companies,
working synergistically to better understand unmet medical needs and the
new technologies that can be used to address them. Co-founded by Professor
Stefan Catsicas, former Vice-President of the Swiss Federal Institute of
Technology (Lausanne), the Tilocor Group promotes an entrepreneurial
approach adapted to the long-term needs of the life science sector.
Currently, Tilocor companies focus on inflammation, infectious diseases and
cancer with specific therapeutic agents that include intracellular
peptides, human antibodies and small chemical entities. More information is
available at www.tilocor.com
