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.

Peter S. Nelson, MD (Clinical Investigator Mentor, Damon Runyon Scholar ‘02-‘04) of Fred Hutchinson Cancer Research Center, Seattle, and colleagues, conducted the first comprehensive assessment of the genome of advanced, lethal prostate cancer. They discovered a number of recurrent genetic mutations common to advanced prostate cancer that may contribute to disease progression and resistance to commonly used therapies. The researchers hope that these findings will lead to development of new strategies for diagnosis and treatment.

Scott A. Armstrong, MD, PhD (Damon Runyon-Lilly Clinical Investigator ‘03-‘08) of Dana-Farber Cancer Institute and Children’s Hospital Boston, and Kornelia Polyak, MD, PhD (Clinical Investigator Award Committee Member) of Dana-Farber Cancer Institute, Boston, 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 for their exceptionally innovative work that has helped to advance the field of cancer research. Dr.

James E. Bradner, MD (Damon Runyon-Rachleff Innovator ‘11-‘13) of the Dana-Farber Cancer Institute, Boston, and colleagues, identified the protein Brd4 as a critical requirement for acute myeloid leukemia (AML) disease maintenance. Brd4 functions to control expression of Myc, a protein frequently disrupted in many cancers. Blocking Brd4, using either RNA interference or a drug called JQ1, led to anti-leukemic effects such as cancer cell death and a delay in disease progression.

Ramesh A. Shivdasani, MD, PhD (Damon Runyon Scholar ‘98-‘99) of Dana-Farber Cancer Institute, Boston, and colleagues discovered a mechanism for how cancer cells become resistant to cetuximab/Erbitux, which is used to treat colorectal cancer or squamous cell cancer of the head and neck. They reported that a protein called ERBB2 allows cells to remain unresponsive to the drug. The study suggests that combining cetuximab with ERBB2-inhibiting drugs could be an effective therapy to both heighten and/or restore the drug’s potency.

Researchers from the Broad Institute, Dana-Farber Cancer Institute, Johns Hopkins Kimmel Cancer Center, the University of Pittsburgh, and the University of Texas MD Anderson Cancer Center, including Joseph A. Califano, III, MD (Damon Runyon-Lilly Clinical Investigator ‘01-‘06), Matthew L. Meyerson, MD, PhD (Damon Runyon Fellow ‘95-‘98), Kenneth W. Kinzler, PhD (Damon Runyon-Rachleff Innovation Award Committee Member), and Todd R.

Hai Yan, MD, PhD (Damon Runyon Scholar ‘05-‘07) of Duke University, Durham, Kenneth W. Kinzler, PhD (Innovation Award Committee Member) of Johns Hopkins University, Baltimore, and colleagues identified two genes that may regulate telomere length in cancer cells. Telomeres are “DNA caps” that protect the ends of chromosomes; telomerase is the enzyme that is normally used to maintain telomeres. These researchers found that rapidly dividing cancer cells can use an alternative means of maintaining telomere length, through the genes ATRX and DAXX.

Jeremy N. Rich, MD (Damon Runyon-Lilly Clinical Investigator ‘04-‘09) of Cleveland Clinic, Cleveland, and colleagues, reported new findings about brain cancer stem cells. Malignant gliomas, aggressive brain tumors with limited treatment options, contain highly tumorigenic subpopulations of cancer stem cells. The researchers identified an enzyme, nitric oxide synthase-2 (NOS2), required for these stem cells to grow and seed tumors. High NOS2 levels correlate with decreased survival in patients with glioma. Drugs that block NOS2 slow brain tumor growth in mice.

Jean Y. Tang, MD, PhD (Damon Runyon Clinical Investigator ‘11-‘14) of Stanford University, Stanford, and colleagues, reported analysis of data from the Women’s Health Initiative. They found that women with a history of non-melanoma skin cancer, such as basal cell or squamous cell cancers, who took a calcium-vitamin D combination developed 57 percent fewer melanomas than women with similar histories who were not given the supplements. In the future, researchers plan to further examine the potential relationship between vitamin D and cancer prevention.

Amanda Paulovich, MD, PhD (Damon Runyon Fellow ‘02-‘03), Peter S. Nelson, MD (Damon Runyon Scholar ‘02-‘04, Clinical Investigator Mentor), and colleagues at Fred Hutchinson Cancer Research Center, Seattle, used a highly sensitive and targeted analytical technology, selected reaction monitoring mass spectrometry, to test candidate protein biomarkers. This technology allows highly specific and sensitive measurement of many proteins from a small drop of blood.