2010 New Discoveries and Honors in Cancer Research
Members of the Damon Runyon scientific circle regularly publish findings on the latest cancer research and are frequently recognized for their contributions to the fight against cancer. Below, you will find new discoveries in cancer research and the most recent honors bestowed upon Damon Runyon Cancer Research Foundation awardees, alumni and friends.
December 17, 2010 > Damon Runyon Scientists and Insights of the Decade
Science magazine published a special issue highlighting Insights of the Decade. Of the ten featured insights from all areas of scientific research, two of them highlight work of current and former Damon Runyon Scientists:
Howard Y. Chang, MD, PhD (Damon Runyon Scholar ‘06-‘08, former Fellowship Sponsor) of Stanford University, Stanford, and John L. Rinn, PhD (Damon Runyon-Rachleff Innovator ‘09-‘11, Current Fellowship Sponsor, Damon Runyon Fellow ‘05-‘07) of Harvard University, Cambridge: “Shining a Light on the Genome’s ‘Dark Matter’”
Sarkis K. Mazmanian, PhD (Damon Runyon-Rachleff Innovator ‘08-‘10) of California Institute of Technology, Pasadena: “Body’s Hardworking Microbes Get Some Overdue Respect”
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December 16, 2010 > Genetics of pediatric brain cancer revealed
A team of researchers including Thomas Curran, PhD, FRS (Former Fellowship Award Committee, Damon Runyon Fellow ‘82-‘84), Daniela S. Gerhard, PhD (Damon Runyon Fellow ‘83-‘85), Peter C. Phillips, MD (Damon Runyon Fellow ‘84-‘86), Hai Yan, MD, PhD (Damon Runyon Scholar ‘05-‘07) reported new findings about the genetic basis of medulloblastoma (MB), the most common malignant brain tumor in children. Kenneth W. Kinzler, PhD (Innovation Award Committee Member) of The Johns Hopkins University School of Medicine, Baltimore, was one of the leading investigators of the study. The researchers sequenced tumor DNA and found that, on average, each tumor had 11 gene alterations; this is 5 to 10 times fewer than in the adult solid tumors that have been sequenced to date. They identified mutations in signaling pathways previously known to be linked to brain cancers (Hedgehog and Wnt pathways), and also discovered novel mutations in genes that regulate activity of other genes through a process called histone methylation. These findings may eventually lead to better targeted therapies for treatment of MB cancers. The report was published in the prestigious journal Science.
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December 3, 2010 > 2010 Louisa Gross Horwitz Prize
Bruce W. Stillman, PhD (Damon Runyon Fellow ‘79-‘81), President of Cold Spring Harbor Laboratory (CSHL), was awarded the 2010 Louisa Gross Horwitz Prize for key research that led to an understanding of the mechanisms involved in the process of DNA replication. This process is critical for normal cells and also goes awry in cancer. The prize has been awarded annually since 1967 for outstanding basic research in biology and biochemistry.
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November 25, 2010 > Restoring p53 in lung cancer
In two separate studies, Melissa R. Junttila, PhD (Damon Runyon Fellow ‘07-‘10) of University of California, San Francisco, and Monte Winslow, PhD (Damon Runyon Fellow ‘06-‘09) of Massachusetts Institute of Technology, Cambridge, reported the results of studies in animal models of non-small cell lung cancer (NSCLC). They observed tumor progression in the absence of the tumor suppressor gene p53. When p53 function was restored, advanced tumor cells were prevented from growing and spreading. In contrast, restoring p53 did not have any effect on benign earlier-stage tumors. The studies suggest that using drugs to activate p53 function may be effective at preventing growth of advanced tumors but will not likely prevent cancer initiation or progression. These findings were published in the journal Nature.
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November 18, 2010 > Genetic basis of common eye cancer identified
Adriana Heguy, PhD (Damon Runyon Fellow ‘86-‘88) of Memorial Sloan-Kettering Cancer Center, New York, and international colleagues participated in a multi-center study that identified novel genetic mutations linked to uveal melanoma, the most common form of eye cancer. They found mutations in either of two related genes, GNAQ and GNA11, in 83% of tumor samples taken from patients with uveal melanoma. There are currently no effective therapies for this cancer once it has metastasized; this new understanding of the disease may lead to targets and treatments in the future. These findings were published in the New England Journal of Medicine.
November 5, 2010 > Presidential Early Career Awards for Scientists and Engineers announced
Muneesh Tewari, MD, PhD (Damon Runyon-Rachleff Innovator ‘09-‘11) of Fred Hutchinson Cancer Research Center, Seattle, was named a recipient of the Presidential Early Career Award for Scientists and Engineers, the highest honor bestowed by the United States government on science and engineering professionals in the early stages of their independent research careers. Awardees are selected for their pursuit of innovative research at the frontiers of science and technology and their commitment to community service.
October 15, 2010 > National Medal of Science recipients named
President Obama named ten eminent researchers as recipients of the National Medal of Science, the nation’s highest scientific honor. Awarded annually, the Medal recognizes individuals who have made outstanding contributions to science and engineering. Stephen J. Benkovic, PhD (Former Fellowship Award Committee Member and Sponsor), Pennsylvania State University, University Park, and Susan L. Lindquist, PhD (Fellowship Sponsor), Whitehead Institute, Massachusetts Institute of Technology, Cambridge, are among this year’s honorees.
October 14, 2010 > Institute of Medicine elects new members
Election to the Institute of Medicine is one of the highest honors that can be earned in the fields of medicine and health. In recognition of their outstanding achievements, 4 members of the Damon Runyon Cancer Research Foundation circle were inducted this month:
Linda S. Birnbaum, PhD (Damon Runyon Fellow ‘73-‘74), National Institutes of Health, Research Triangle Park
Titia de Lange, PhD (Former Fellowship Sponsor), The Rockefeller University, New York
Jennifer A. Doudna, PhD (Fellowship Sponsor, Former Fellowship Award Committee Member), University of California, Berkeley
Kevan M. Shokat, PhD (Innovation Award Committee Member), University of California, San Francisco
September 30, 2010 > New NIH High-Risk Research Awards announced
The intent of the NIH High-Risk Research Awards is to encourage investigators to explore bold ideas that have the potential to catapult fields forward and speed the translation of research into improved health. We congratulate the Damon Runyon scientists who are recipients of these awards.
Transformative R01 Award:
Madhav Dhodapkar, MD (Damon Runyon-Lilly Clinical Investigator ‘02-‘07), Yale Cancer Center, New Haven; Richard A. Flavell, PhD (Former Fellowship Award Committee Member), Yale University School of Medicine, New Haven; X. Sunney Xie, PhD (Current Fellowship Sponsor), Harvard University, Cambridge
Pamela J. Bjorkman, PhD (Former Fellowship Sponsor), California Institute of Technology, Pasadena; Stephen W. Fesik, PhD (Former Innovation Award Committee Member), Vanderbilt University School of Medicine, Nashville; Jun O. Liu, PhD (Damon Runyon Fellow ‘91-‘93), Johns Hopkins University School of Medicine, Baltimore
September 30, 2010 > Four subtypes of common lung cancer identified
C. Ryan Miller, MD, PhD (Damon Runyon-Genentech Clinical Investigator ‘09-‘12) of University of North Carolina, Chapel Hill, and colleagues, genetically characterized nearly 400 patient samples of lung squamous cell carcinoma (SCC). They defined four subtypes - primitive, classical, secretory, and basal. The primitive subtype correlates with worse patient survival and recurrence rates, suggesting that more aggressive therapies may be more appropriate for these patients. These findings were published in the journal Clinical Cancer Research.
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September 24, 2010 > New finding may help to reduce graft-versus-host-disease
Ivan Maillard, MD, PhD and Yi Zhang, MD, PhD (Damon Runyon-Rachleff Innovators ‘09-‘11) of University of Michigan, Ann Arbor, reported that Notch signaling is a critical regulator of T cell responses mediating graft-versus-host disease (GVHD), a life-threatening immune response that remains the major barrier to the success of allogeneic hematopoietic stem cell transplantation (HSCT). The researchers demonstrated that inhibition of Notch signaling in donor T cells significantly reduced GVHD severity and mortality in mouse models of HSCT. In addition, Notch-deficient T cells remained able to efficiently kill cancer cells. This resulted in the elimination of the tumor cells without causing GVHD. The study was published in the scientific journal Blood.
September 21, 2010 > 2010 Lasker Award winners announced
The 2010 Lasker~DeBakey Clinical Medical Research Award honors Napoleone Ferrara, MD (Damon Runyon-Rachleff Innovation Award Committee Member) of Genentech. He is recognized “for the discovery of Vascular Endothelial Growth Factor (VEGF) as a major mediator of angiogenesis and the development of an effective anti-VEGF therapy for wet macular degeneration (AMD), a leading cause of blindness in the elderly.” His work led to the development and success of the drugs Lucentis® for the treatment of wet AMD and Avastin® for treatment of colorectal and other cancers. The Lasker Awards will be presented at a ceremony on October 1 in New York City.
August 26, 2010 > Targeted therapy success in metastatic melanoma
Grant A. McArthur, MBBS, PhD, FRACP (Damon Runyon Fellow ‘95-‘98) and colleagues at the Peter MacCallum Cancer Institute, Melbourne, Australia, and a team of U.S. researchers reported the success of a Phase I clinical trial of the drug PLX4032 in treatment of metastatic melanoma. Mutation of a protein called BRAF causes the protein to become overactive in more than half of all melanomas. PLX4032 inhibits BRAF, resulting in complete or partial tumor regression in over 80% of patients with mutated BRAF. Patients begin to feel better within a week of starting treatment, giving them a significantly improved quality of life. The results were reported in the New England Journal of Medicine.
August 24, 2010 > Combined therapies block brain tumor recurrence
Alonzo H. Ross, PhD (Damon Runyon Fellow ‘77-‘78) of the University of Massachusetts Medical School, Worcester, discovered that combining chemotherapy (temozolomide, TMZ) with a targeted therapy that blocks Notch signaling (γ-secretase inhibitor, GSI) blocks glioblastoma brain tumor recurrence in mice. In patients, these tumors are typically treated with surgery, radiation and TMZ, but these therapies ultimately fail due to tumor recurrence. GSIs are thought to block the cancer stem cells that resist chemotherapy/radiation and allow tumor recurrence. The researchers hope to ultimately translate these findings into the clinic. This study was published in the journal Cancer Research.
August 17, 2010 > New understanding of lung tumor resistance to Tarceva
Raffaella Sordella, PhD (Island Outreach Foundation Innovator ‘10-‘12) of Cold Spring Harbor Laboratory, Cold Spring Harbor, reported the discovery of a subpopulation of cells in non-small cell lung cancer (NSCLC) tumors that are intrinsically resistant to the targeted therapy erlotinib/Tarceva. These cells have features suggestive of a fate change termed epithelial-to-mesenchymal transition (EMT), and the researchers showed that these features are dependent on signaling by TGF-β and secretion of a factor called IL-6. Both TGF-β and IL-6 trigger inflammation. Interestingly, this study suggests that inflammation (e.g., in the tumor microenvironment) can reduce the tumor response to Tarceva; this represents an important new understanding of how tumor cells develop resistance. These findings were published in the journal Proceedings of the National Academy of Sciences.
August 15, 2010 > Nanoparticles for drug delivery
Darrell J. Irvine, PhD (Damon Runyon Fellow ‘00-‘01) and colleagues at Massachusetts Institute of Technology, Cambridge, reported a new approach to encase drugs in nanoparticles for better targeting of immune therapies to tumors. They demonstrated success of this technique in mice and hope the particles can be used in clinical trials in cancer patients within the next two to three years. The approach could also potentially be applied to targeted delivery of chemotherapy agents. These findings were published in the journal Nature Medicine.
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August 12, 2010 > Novel findings about non-coding lincRNAs
John L. Rinn, PhD (Damon Runyon-Rachleff Innovator ‘09-‘11, Damon Runyon Fellow ‘05-‘07) of Harvard Medical School and the Broad Institute, Boston, Laura D. Attardi, PhD (Damon Runyon Scholar ‘02-‘04) of Stanford University, Stanford, and colleagues, discovered that one particular non-coding RNA, lincRNA-p21, acts as a repressor of p53-dependent gene expression and apoptosis (cell death). p53 is the most commonly-mutated gene in human cancers. These findings were published in the journal Cell. In a separate study, Howard Y. Chang, MD, PhD (Damon Runyon Scholar ‘06-‘08, former Fellowship Sponsor) and colleagues at Stanford University, Stanford, reported that lincRNAs may function by serving as scaffolds to bring together select enzymes that regulate the expression of target genes by modifying histones. This report was published in the journal Science.
August 4, 2010 > Molecular diagnostic technology using single cells
Hong Wu, MD, PhD (Damon Runyon Fellow ‘92-‘95, Former Sponsor) and a team of researchers at the University of California, Los Angeles, have developed a new technology that can measure signaling pathway levels in a single cell from tissues, including brain tumors. The new technology, microfluidic image cytometry (MIC), combines microfluidics and microscopy-based cell imaging. These molecular “fingerprints” are a new advance in diagnostics that could ultimately help physicians predict patient prognosis and guide personalized treatment. This study was published in the journal Cancer Research.
June 25, 2010 > Virus plus genetic mutation promotes Crohn’s disease
Ken Cadwell, PhD (Lallage Feazel Wall Fellow ‘08-‘11) and colleagues at Washington University, St. Louis, reported that the combination of a genetic mutation in Atg16L1 plus a specific viral infection induces Crohn’s disease, an inflammatory disease of the gut. The mutation alone is not sufficient to promote the disease. In addition, their research suggests that the genetic and viral combination harms the gut microbial community. Treatment with an antibiotic clears out the gut microbes and eliminates disease symptoms in mice. This study indicates that viruses may play an important role in disease onset. These findings were published in the journal Cell.