Medical Device Daily Washington Writer

After several years of a flat budget, the National Cancer Institute (NCI) received a nearly 3% budget increase this fiscal year and $1.3 billion from the economic stimulus package, which will significantly boost the number of grants awarded over the next few years, leading to an acceleration of cancer research, said NCI Director John Niederhuber.

The American Reinvestment and Recovery Act (ARRA) is a "chance to enhance and to change cancer science," he said Monday at the annual meeting of the American Association for Cancer Research in Denver.

Niederhuber noted that cancer researchers have not been immune from the effects of the economic downturn.

"Scientists everywhere have felt the strain of NCI budgets that, for four years, have received no increase," he said. "You have felt the strain of the up-front downward negotiation of your grants, on average, some 17% to 21%. We have all worried that the pace of cancer research is becoming imperiled and that biomedical research will no longer attract the best and the brightest," Niederhuber added.

However, he said, the ARRA stimulus funds will now give cancer researchers "the chance to be visionary" and "move cancer research from the accumulation of scientifically exciting genomic data to a new way of approaching prevention, diagnosis and therapy and to ensure access to our latest science for all."

Niederhuber explained that NCI must ensure that stimulus funds not be mixed with the congressionally appropriated budget funds.

"Each must be accounted for separately," with the NCI maintaining separate account numbers and accounting procedures, he said.

"There are different rules, in many cases, of what can be funded from which pot of money," Niederhuber said, adding that the ARRA funds come with requirements of "unprecedented level of transparency and accountability.

"Indeed, recipients of the stimulus funds will also have some stringent requirements, particularly around reporting on your stewardship of these dollars," he said.

The NCI is taking a series of steps to increase the support for research project grants (RPG), particularly the investigator initiated R0I, Niederhuber said. The so-called RPG payline – the line of demarcation between grants that are funded and not funded, based solely on peer review – will be "rising considerably," he said.

Using NCI's increased fiscal 2009 appropriation, NCI has raised the payline from last year's 12 percentile to the 16 percentile for the standard five-year grants, which Niederhuber told reporters later was "one of the highest we've had now in quite a few years."

Through coordinated, but separate administrations of stimulus and appropriated funds, NCI will raise the payline to the 25th percentile, using a combination of two- and four-year grants, with concurrent increases in the grant payline for young, first-time investigators, he said.

For instance, Niederhuber told reporters, the NCI plans to fund applicants between the 16th and the 18th percentile for four years using the stimulus dollars for first two years and the appropriated budget funds for the third and fourth years.

He noted that instead of five years, those grantees will have only four years of support.

Between the 18th and 25th percentile, the NCI will fund grants that have been reviewed and in the queue for 2009 for two years.

Of that last group, he said, the agency plans to choose applicants it deems as "very meritorious" with "outstanding science" that fills some of the gaps in the research portfolios.

"They are grants that aren't just doing the same thing that other applicants are doing," Niederhuber said, adding that they should be those that bring something "interesting and exciting" to cancer research.

"While the numbers are not yet firm, it is clear that there will be a marked increase in the number of principal investigators studying cancer," he said.

Scientists should not simply see the economic stimulus package as "more dollars toward business as usual," Niederhuber said.

"We must look to new ideas, new methods, new areas of cooperation and collaboration," with none more important than fostering the next generation of cancer science and cancer scientists, he said.

He noted that the NCI has a plan to fund early stage physician scientist and PhD investigators committed to careers in translational cancer research. "These start-up packages will assist young faculty members in establishing laboratories, in creating a foundation for a career of excellence," Niederhuber said.

A parallel program will be available to investigators at the NCI-Designated Cancer Centers and at institutions funded through the Minority Institution/Cancer Center Partnership program, he added.

"We are surrounded today by transforming technologies that are changing the nature of diagnosis, of prevention, of early detection," Niederhuber said.

He noted that the NCI has outlined so-called signature projects – areas of investigation positioned to accelerate discovery in a short number of years. Among the signature projects, Niederhuber said, are the Cancer Genome Atlas (TCGA) and the Therapeutically Applicable Research to Generate Effective Treatments (TARGET).

TCGA has established characterization and sequencing centers, along with programs in data management, bioinformatics, and computational analysis. TCGA has sequenced more than 200 tumors in glioblastoma, along with lung and ovarian cancers. In glioblastoma alone, TCGA has identified three genes not previously associated with the cancer and delineated as many as four subtypes of glioblastoma, Niederhuber said, adding that NCI has the goal of identifying all of the relevant genomic alterations in 20 to 25 major tumor types.

The TARGET pediatric cancer genomics program will apply next-generation sequencing to at least 100 tumor specimens per childhood cancer, he said.

Programs like TCGA and TARGET, along with numerous other whole-genome association studies using large population cohorts to assess germline risk, are generating a "mountain of data and revealing potential genetic defects that occur within cancer," Niederhuber declared.

However, he said, while "scientifically fascinating and intellectually groundbreaking," those data primarily remain raw information that must be developed into knowledge of causal pathways and functional biology.

Through the development of new probes and assays of biologic function, the NCI will convert the "undruggable" into "functional pathways" with clearly defined targets for manipulating those pathways, Niederhuber vowed.

"Moving from data, to function, to target, to therapy will not be simple, nor will it be easy or inexpensive," he said.

But, he said, the NCI is committed to designing and constructing a personalized cancer care drug development platform, which Neiderhuber said also is one of the agency's signature initiatives.

At the beginning of the platform will be functional biology centers – a virtual network of investigators who will take promising genetic alteration identified in TCGA and answer specific questions about biologic function and potential druggable targets.

The NCI also is taking steps to create the first of a small national network of patient characterization centers, which will serve wide geographic areas, bringing together genomics and genetics, proteins and proteomics, all in the interest of matching a genetically characterized patient and his or her characterized tumor to appropriate and optimal therapeutic solutions.

The NCI's platform is a "vision for a new way of thinking," Niederhuber said. But, he insisted, "It is not an unrealistic concept. It is an action plan, a blueprint for what we are beginning to assemble this year, making the optimal use of every new resource. It is a blueprint for 21st century translation."

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