The pathway less traveled

TGen, Scottsdale Healthcare researchers use computer simulations to validate treatment targets for lung cancer

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PHOENIX, Ariz.—Using computer modeling, researchers at theTranslational Genomics Research Institute (TGen) and Scottsdale Healthcare haveuncovered lung cancer "pathways" that ultimately could become targets for newdrugs.
According to Dr. Glen Weiss, director of thoracic oncologyat TGen Clinical Research Services at Scottsdale Healthcare, the study,published in the Journal of Thoracic Oncology, showed the value of conducting computer modeling, or insilico research.
"The focus is to mine the publicly available gene expressionmicroarray data sets for shared common pathways, looking at identifying new andpossibly unrealized targets for small-cell cancer and large-cell cancertreatments," notes Weiss.
Scottsdale Healthcare and TGen have partnered ongroundbreaking cancer research since 2005. The partnership allows molecular andgenomic discoveries made by TGen and others around the world to reach thepatient bedside through Scottsdale Healthcare's Virginia G. Piper Cancer Centeras quickly as possible through clinical trials with agents directed at specifictargets in patients' tumors.
The researchers hope that over time, in silico research will help lower healthcare costs whilespeeding up the process of turning scientific discoveries into treatments forpatients. Weiss notes that by using in silico research, investigators can design more focusedlaboratory experiments, hopefully with more precision and efficiency.
"There are pathways that you can identify just from insilico analysis. And we can use these typesof tools to explore treatments for patients, down the road," says Weiss, anassociate investigator in TGen's Cancer and Cell Biology division and thesenior author of the paper.
Weiss says the expectation is that in silico research will yield targets for further clinical andlaboratory research.
The study sought to identify metabolic pathways that couldbe targeted by drugs in patients with both small-cell and large-cell lungcancers. Small-cell lung cancer represents about 15 percent of all lungcancers. The rest are classified as non-small cell lung cancer, of whichlarge-cell lung cancer represents about 10 percent. The study used publiclyavailable data sets, searching for connections that may have been previouslyoverlooked.
"By utilizing what is available, other investigators canmine these datasets to lend support for their hypotheses or help focuslaboratory experiments," notes Weiss. "Because it may be costly and challengingto assemble large databases of gene expression data in a particular cancertype/situation, it is important to make these databases accessible to thepublic."
Weiss says that within those datasets, there are commonpathways.
"We point out some examples that provide someproof-of-principle from the in silicosearch," adds Weiss, who was joined in his research by TGen's Dr. ChrisKingsley and by Dr. Anoor Paripati of the Scottsdale Clinical ResearchInstitute at Scottsdale Healthcare.
As an example, the study cites one particular signalingpathway, Wnt/ß-catenin, that could be targeted by two drugs, Vorinostat andDasatinib, both of which are under study in clinical trials.
"This is an exploration of the publicly available data setsin an attempt to answer a new question. It shows that you can look at pathwaysand identify targets," Weiss points out. "We did our validation by looking atwhat's been tested, or what's available already."
In silico research,which is far less costly than conducting genetic profiling analysis of cancertumors, is expected to become more common as the National Cancer Instituteramps up its cancer Biomedical Informatics Grid, also known as caBIG. Suchresearch should lead to targets for further laboratory and clinical research,and also should help clinicians provide more personalized treatment forpatients, Weiss says.
"There is going to be a wealth of profiling data out therein the near future. You can then apply techniques like this, and hopefullydesign smarter clinical trials to find the drugs that would work," Weiss notes."Like other clinical research conducted at Scottsdale Healthcare, this studywill be measured by clinically validated results."
Report heralds TGen's annual economic impact on Arizonaeconomy
PHOENIX—A report issued in late September by research firmTripp Umbach estimates that the Translational Genomics Research Institute(TGen) provides Arizona with an annual total economic impact of $77.4 million.The firm also estimates that including spin-off businesses andcommercialization of TGen-led research, TGen's total annual economic impactwill grow to $321.3 million by 2025.
With these results, TGen has outpaced all previousperformance marks and projections made in a December 2006 economic impactreport by Tripp Umbach.
The new report concludes that TGen operations in 2008 produced$8.09 for every $1 invested by the state of Arizona, 461 full-time jobs(directly and indirectly), $2.7 million in state taxes and a direct annualeconomic impact of $44.5 million.
When the impact of TGen-generated business spin-offs andcommercialization are included, the study shows that TGen in 2008 produced$14.07 for every $1 invested by the state, $5.7 million in taxes and $77.4million in total annual economic impact.
By 2025, the report predicts, TGen operations will return$30.20 for every $1 invested by the state, resulting in 2,332 jobs, $13.4million in state taxes and an annual economic impact of $166.1 million.Including projected business spin-offs and commercialization, the report says,TGen would return $58.42 for every $1 invested by the state, create 4,116 jobs,generate $27.4 million in taxes and produce a total annual economic impact of$321.3 million.
"TGen has certainly kept its promise to the state of Arizona to be astrong economic engine,'' said Paul Umbach, president of Pittsburgh-based TrippUmbach, in a statement. "Our updated analysis shows dramatic increases ineconomic, employment, and government revenue impacts on Arizona's economy. As aresult of TGen's better-than-expected performance over the past two years, ourprojected impact numbers for 2015 and 2025 are also significantly stronger. Itis clear from our updated analysis that commercial spin-off activities fromTGen are rapidly having a positive economic impact on the Arizona economy atjust a time when adding jobs is so important."

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