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
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