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NCI Renews Provocative Questions Program

NEW YORK (GenomeWeb News) – A year after it launched its effort to fund research that uses the latest technologies to tackle particularly interesting or difficult problems in cancer research and treatment, the National Cancer Institute has recently awarded millions to fund new projects and has renewed the program for another year.

The NCI's Provocative Questions (PQ's) project, which seeks to stimulate research projects that address specific problems that were identified as ripe for exploration by the scientific community, has recently funded a number of investigators and has issued several new requests for funding for new projects.

The PQs that NCI posted last year and received funding involve a range of disciplines, including genomic medicine, computational biology, and molecular biology. When the first round of the PQ program is completed, NCI plans to have provided $22 million to investigators around the country.

Under the renewed PQ program, the institute will provide awards of up to $275,000 for one year for projects to answer an updated list of provocative questions. These new PQ grants will be divided by theme into four groups.

Group A projects will fund studies that answer unsolved problems related to behavior, exposure, and cancer risk and cancer development; Group B studies will relate to tumor development or recurrence; Group C questions will focus on cancer detection, diagnosis, and prognosis; and Group D projects will seek to answer problems related to cancer treatments.

The specific questions to be addressed within these thematic groups should inspire research projects that use "innovative strategies to solve specific problems and paradoxes in cancer research" that were identified by NCI, the institute said in its funding announcement.

"Some of these [PQs] stem from intriguing but older, neglected observations that have never been adequately explored. Other PQs are built on more recent findings that are perplexing or paradoxical, revealing important gaps in current knowledge. Finally, some PQs reflect problems that traditionally have been thought to be intractable but that now may be open to investigations using new strategies and recent technical advances," NCI explained.

For example, the PQs NCI developed for Group B seek to find out why second, independent cancers occur at higher rates in patients who have survived a primary cancer compared to a cancer-naïve population. The institute also asks if researchers can develop approaches to discriminate between "driver" and "passenger" epigenetic events during tumor development, and further asks a question about the order in which mutations or epigenetic changes occur and how that can alter cancer phenotypes or affect the efficacy of targeted therapies.

The list of PQs for Group B can be found here.

Under the first-year program, NCI has now awarded grants to fund 50 projects pursuing the PQs through a wide array or techniques and approaches.

For example, at the University of New Mexico Cancer Center, researchers will use a grant of $594,000 to fund efforts to understand how RNA splicing in tumors may be involved in cancer formation. They will use the Ion Proton Genome Sequencer to sequence the RNA in samples to determine which proteins were made by leukemia cells and then will analyze that data combined with patient outcomes to find out if the splicing contributes to the formation of the cancers.

Columbia University scientists won a $332,000 grant to study DNA methylation and tumor cell apoptosis. They plan to re-evaluate the role of abnormal genomic methylation patterns in breast cancer to find out if methylation biomarkers identified through whole-genome methylation profiling could be useful in early cancer diagnosis.

University of Illinois-Urbana Champaign scientists won a $180,000 grant to use nanopore and deep sequencing to measure how the carcinogen Benzo(a)pyreen (BaP), found in polluted air, smoked food, and tobacco smoke, can lead to mutations that can in turn cause cancer.

Scientists at the University of Wisconsin – Madison will use a grant of $196,000 to monitor tumors as they progress by collecting biopsies and conducting molecular analysis with DNA microarrays and to compare adenocarcinomas with adenomas that do not progress. The hope is to find biomarkers that can predict tumor progression and inform development of personalized screening schedules and preventive strategies for each patient.

University of Pittsburgh scientists won a $199,000 PQ grant to develop computational methods for identifying infectious agents that contribute to cancer. They plan to merge gene expression and metagenomics data to find out if novel metagenomics sequences representing undiscovered microbes are expressed in tumors. They also will develop computational tools to isolate any uncharacterized viruses, bacteria, or other organisms and find out if they are associated with cancer.

NCI also used PQ funding to support research projects using or based on varying levels of 'omics at a number of other institutions, including studies of molecular pathways linking obesity and tumorigenesis at the University of Texas M.D. Anderson Cancer Center, of epigenetic drivers of cancer at the University of Southern California, and of the mechanisms underlying colorectal cancer risk in inflammatory bowel disease.

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