Don X. Nguyen, PhD (Damon Runyon Fellow ‘05-‘08) and colleagues in the lab of Joan Massagué, PhD (Former Fellowship Award Committee), at Memorial Sloan-Kettering Cancer Center, New York, identified a new process termed “tumor self-seeding” by which aggressive circulating tumor cells (CTCs) return to recolonize their tumors of origin.  The researchers found that self-seeding can accelerate tumor growth and angiogenesis through activation of cytokines IL-6 and IL-8, which attract the most aggressive CTCs back to the original tumor, and factors FSCN1 and MMP1, which mediate the physical infiltration of CTCs into a tumor.  These findings may lead to new targeted therapies that interfere with the self-seeding process and thus slow or prevent tumor progression.  This study was published in the journal Cell.

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Nathanael S. Gray, PhD (Damon Runyon-Rachleff Innovator ‘08-‘10) and colleagues at the Dana-Farber Cancer Institute, Boston, identified a new agent that can act on non-small cell lung cancers that have become resistant to the drugs Iressa® and Tarceva®.  Each of these drugs targets a protein called the epidermal growth factor receptor (EGFR) kinase, which promotes cell growth.  The new compound, WZ4002, is highly specific for the form of EGFR in cancer cells while not affecting normal healthy cells; for this reason, the compound is less likely to produce side effects.  In the future, this compound may be an effective treatment for lung cancer patients.  These findings were published in the journal Nature.    

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Albert C. Koong, MD, PhD (Damon Runyon-Lilly Clinical Investigator ‘02-‘07) of Stanford University School of Medicine, Stanford, reported the use of multiple simultaneous measurements of biomarkers for more accurate and sensitive diagnosis of pancreatic cancer.   The studies identified a panel of biomarkers CA19-9, OPN and CHI3L1 that improves accuracy of pancreatic cancer diagnosis compared to CA19-9 alone.  Levels of two markers, CEA and CA125, can predict survival for advanced pancreatic cancer patients.  These findings were published in the Journal of Translational Medicine. 

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Charles M. Perou, PhD (Clinical Investigator Mentor), UNC Lineberger Comprehensive Cancer Center, Chapel Hill, has been awarded the 2009 Outstanding Investigator Award for Breast Cancer Research by the American Association for Cancer Research (AACR).  He is honored for his important work defining molecular subtypes of breast cancer and associated risk factors; these findings have helped physicians to individualize treatment of each patient’s cancer.   

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James A. Wells, PhD (Damon Runyon Fellow ‘80-‘82, Former Fellowship Award Committee Member and Former Sponsor) of the University of California, San Francisco, was named the recipient of the 2010 American Society for Biochemistry and Molecular Biology-Merck Award for his pioneering studies in the field of protein engineering.  His research has led to fundamental discoveries as well as pharmaceutical products potentially important for treatment of cancer and other diseases.      

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Jeremy N. Rich, MD (Damon Runyon-Lilly Clinical Investigator ‘04-‘09), Bruce Sullenger, PhD (Damon Runyon Fellow ‘91-‘93) and Xiao-Fan Wang, PhD (‘87-‘89) at Duke University Medical Center, Durham, reported the role of the Notch signaling pathway in cancer stem cell resistance.  They demonstrated that Notch is the likely reason that cancer stem cells resist radiation better than other cancer cells.  In a petri dish, blocking Notch activity in glioma brain tumor cells with a drug called a gamma-secretase inhibitor makes the cells susceptible to radiation.  These results suggest that a combination therapy of Notch inhibitor drugs plus radiotherapy could be very effective means of controlling tumors.  The findings were published in the journal Stem Cells.

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Sreekanth H. Chalasani, PhD (Damon Runyon Fellow ‘04-‘07) of The Rockefeller University, New York, has been named one of eight winners of the 2009 New York Academy of Sciences Blavatnik Award for Young Scientists.  The annual Blavatnik Awards recognize highly innovative, impactful, and interdisciplinary accomplishments in the life sciences, physical sciences, and engineering. 

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John M. Pagel, MD, PhD (Damon Runyon-Lilly Clinical Investigator ‘05-‘10) of the Fred Hutchinson Cancer Research Center, Seattle, reported the success of a Phase I clinical trial testing a novel combination of low-intensity chemotherapy, targeted radiation delivery by an antibody and a stem cell transplant.  This regimen resulted in remission for patients with advanced acute myeloid leukemia or a pre-leukemia syndrome.  These are patients for whom there previously had been no other treatment options.  The report was published in the journal Blood. 

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John L. Rinn, PhD (Damon Runyon-Rachleff Innovator ‘09-‘11 and Damon Runyon Fellow ‘05-‘07) of Harvard Medical School and the Broad Institute, Boston, was named one of this year’s “Brilliant 10” by Popular Science magazine.  His research has helped uncover a new class of RNA called lincRNA (large intervening non-coding RNA).  The list recognizes the nation’s top scientists under age 40 and appears in the November issue of the magazine. 

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Elaine V. Fuchs, PhD (Damon Runyon Board Member, Damon Runyon Fellow ‘77-‘79) of The Rockefeller University, New York, has been named the North American recipient of the 2010 L’ORÉAL-UNESCO Award for her contributions to our knowledge of skin biology and skin stem cells.  This year these international awards recognize and promote five exceptional women who, by the excellence of their research, contribute to the advancement of science.

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Hong Wu, MD, PhD (Damon Runyon Fellow ‘92-‘95, Former Sponsor) of UCLA’s Jonsson Comprehensive Cancer Center, Los Angeles, demonstrated that the loss or reduction of the tumor suppressor gene PTEN is involved in the transformation of benign nerve tumors called neurofibromas into a deadly form of sarcoma, malignant peripheral nerve sheath tumors.  In the future, the researchers plan to screen drugs that may be able to target the PTEN pathway and block signals that instruct cells to change from a benign state to a malignant one.  These findings were published in the journal Proceedings of the National Academy of Sciences.

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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, 10 members of the Damon Runyon Cancer Research Foundation circle were inducted this October:

Russ B. Altman, MD, PhD (Former Damon Runyon Sponsor), Stanford University, Stanford, California

Patrick O. Brown, MD, PhD (Damon Runyon Sponsor), Stanford University, Stanford, California

Martin Chalfie, PhD (Former Damon Runyon Sponsor), Columbia University, New York, New York

Thomas Curran, PhD (Damon Runyon Fellow ‘82-‘84 and Fellowship Award Committee Member ‘93-‘97), University of Pennsylvania, Philadelphia, Pennsylvania

Tyler Jacks, PhD (Fellowship Award Committee Member and Damon Runyon Sponsor), Massachusetts Institute of Technology, Cambridge, Massachusetts

Alexandra L. Joyner, PhD (Fellowship Award Committee Member ‘97-‘01), Memorial Sloan-Kettering Cancer Center, New York, New York

Michel C. Nussenzweig, PhD (Fellowship Award Committee Member ‘00-‘02), The Rockefeller University, New York, New York

Gary B. Ruvkun, PhD (Fellowship Award Committee Member ‘01-‘05 and Damon Runyon Sponsor), Massachusetts General Hospital, Boston, Massachusetts

Amita Sehgal, PhD (Fellowship Award Committee Member and Damon Runyon Sponsor), University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania

Ralph Weissleder, MD, PhD (Damon Runyon Clinical Investigator Mentor and Former Damon Runyon Sponsor), Massachusetts General Hospital, Boston, Massachusetts

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Thomas A. Steitz, PhD (Former Damon Runyon Sponsor) of Yale University, New Haven was awarded the 2009 Nobel Prize in Chemistry “for studies of the structure and function of the ribosome.”  He shares the award with Venkatraman Ramakrishnan, PhD, of MRC Laboratory of Molecular Biology, Cambridge, United Kingdom, and Ada E. Yonath, PhD, of Weizmann Institute of Science, Rehovot, Israel.  Based upon the information in DNA, ribosomes make proteins; there are tens of thousands of proteins in the body, all providing different functions.  They build and control life at the chemical level.  Using X-ray crystallography, the awardees showed what the ribosome looks like and how it functions. 

As the target of many known antibiotics, the bacterial ribosome is a structure of major therapeutic importance. It is hoped that an understanding of precisely how antibiotics interact with the ribosome will allow the design of new antibiotics to tackle drug-resistant bacteria. Each of the awardees has imaged the molecular interactions between ribosomes and antibiotics, providing key data to help guide drug design of new antibiotics.

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Elizabeth H. Blackburn, PhD (Innovation Award Committee Member and Former Sponsor) of the University of California, San Francisco, and Jack W. Szostak, PhD (Former Damon Runyon Sponsor) of Massachusetts General Hospital, Boston, were awarded the 2009 The Nobel Prize in Physiology or Medicine for the discovery of “how chromosomes are protected by telomeres and the enzyme telomerase.”

They share the award with Carol W. Greider, PhD, of Johns Hopkins University School of Medicine, Baltimore.  The long DNA structures that carry our genes are packed into chromosomes, and telomeres are the caps on their ends.  Drs. Blackburn and Szostak discovered that a unique DNA sequence in the telomeres protects the chromosomes from degradation. Drs. Greider and Blackburn identified telomerase, the enzyme that makes telomere DNA. These findings explained how the ends of the chromosomes are protected by the telomeres and that they are made by telomerase.

If the telomeres are shortened, cells age. Conversely, if telomerase activity is high, telomere length is maintained, and cellular senescence is delayed such as in cancer cells, which can be considered to have eternal life. Certain other inherited diseases are characterized by a defective telomerase, resulting in damaged cells. This award recognizes the discovery of a fundamental mechanism in the cell, which stimulated the development of new therapeutic strategies.

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Matthew L. Meyerson, MD, PhD (Damon Runyon Fellow ‘95-‘98 and Current Fellowship Sponsor) of the Dana Farber Cancer Institute, Boston, and David M. Sabatini, MD, PhD (Former Fellowship Sponsor) of the Whitehead Institute, Cambridge, are two of this year’s recipients of the Paul Marks Prize for Cancer Research.  The awards recognize three young investigators under the age of forty-six who have taken significant steps toward advancing the understanding of cancer. 

Dr. Meyerson is a leader in the field of cancer genomics and plays a key role in the Cancer Genome Atlas (TCGA) project that aims to improve the understanding of the molecular basis of cancer.  One of his most significant discoveries is the identification of mutations in the epidermal growth factor receptor (EGFR) gene that drive lung cancer and its response to the targeted therapies erlotinib (Tarceva®) and gefitinib (Iressa®).  He has also studied other cancer-related genes that function in some types of leukemia, lung cancer, neuroblastoma, glioblastoma and endometrial cancer. His laboratory is also identifying cancer-causing microbes.

Dr. Sabatini identified the mTOR protein kinase, a key protein in regulating cell growth, proliferation, and survival. He has focused on determining how the mTOR pathway relates to cancer.  His findings have contributed to two drugs, temsirolimus (Torisel®) and everolimus (Afinitor®), both of which target the mTOR pathway and are approved for the treatment of kidney cancer.  His current work is examining how metabolism affects cancer.

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The NIH announced 115 new High-Risk Research Awards totaling $348 million: 42 Transformative R01 Awards, 18 Pioneer Awards, and 55 New Innovator Awards for early-stage investigators.  The intent of these 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:
• Benjamin F. Cravatt, PhD (Fellowship Award Committee Member), The Scripps Research Institute, La Jolla
• Linda G. Griffith, PhD (Innovation Award Committee Member), Massachusetts Institute of Technology, Cambridge
• Muneesh Tewari, MD, PhD (Damon Runyon-Rachleff Innovator ‘09-‘11, Damon Runyon Fellow ‘01), Fred Hutchinson Cancer Research Center, Seattle
• Mark J. Zylka, PhD (Damon Runyon Fellow ‘00-‘03), University of North Carolina, Chapel Hill

Pioneer Award:
• Markus W. Covert, PhD (Damon Runyon Fellow ‘04-‘06), Stanford University, Stanford

New Innovator Award:
• Alla Grishok, PhD (Damon Runyon Fellow ‘02-‘05), Columbia University, New York
• John L. Rinn, PhD (Damon Runyon-Rachleff Innovator ‘09-‘11, Damon Runyon Fellow ‘05-‘07), Broad Institute of MIT and Harvard, Boston
• Pardis C. Sabeti, MD, PhD (Damon Runyon Fellow ‘04-‘06), Harvard University, Cambridge
• Wenying Shou, PhD (Damon Runyon Fellow ‘02-‘05), Fred Hutchinson Cancer Research Center, Seattle

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Nine eminent researchers were named 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.  Elaine V. Fuchs, PhD (Damon Runyon Board Member, Damon Runyon Fellow ‘77-‘79) of The Rockefeller University, New York, and JoAnne Stubbe, PhD (Fellowship Sponsor) of Massachusetts Institute of Technology, Cambridge, are among this year’s honorees. 

Dr. Fuchs is being honored “for her pioneering use of cell biology and molecular genetics in mice to understand the basis of inherited diseases in humans and her outstanding contributions to our understanding of the biology of skin and its disorders, including her notable investigations of adult skin stem cells, cancers and genetic syndromes.”  Dr. Stubbe is being honored “for her groundbreaking experiments establishing the mechanisms of ribonucleotide reductases, polyester synthases, and natural product DNA cleavers — compelling demonstrations of the power of chemical investigations to solve problems in biology.”

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The 2009 Lasker~DeBakey Clinical Medical Research Award honors Brian J. Druker, MD (Former Clinical Investigator Award Committee Member) of Oregon Health & Science University, Portland, and Charles L. Sawyers, MD (Former Clinical Investigator Mentor) of Memorial Sloan-Kettering Cancer Center, New York.  They are recognized “for the development of molecularly-targeted treatments for chronic myeloid leukemia, converting a fatal cancer into a manageable chronic condition.”  Their work led to the development and success of the drug Gleevec.  The Lasker Awards will be presented at a ceremony on October 2 in New York City.

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Neal G. Copeland, PhD (Damon Runyon Fellow ‘77-‘79) and Nancy A. Jenkins, PhD (Former Fellowship Sponsor) of the Institute of Molecular and Cell Biology, Singapore, and Luis F. Parada, PhD (Damon Runyon Fellow ‘85-‘86, former Fellowship Advisory Committee Member) of University of Texas Southwestern, Dallas, and colleagues reported a new strategy to study the mechanism of drug resistance in leukemia and other cancers.  The researchers developed an animal model that allows them to identify new genetic mutations that are linked to resistance.  A greater understanding of resistance will enable the development of ways to anticipate and overcome drug resistance, leading to more effective therapies.  This report was published in the journal Nature.  

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