New Discoveries and Honors
Read about the latest discoveries by Damon Runyon scientists and honors received by scientists in the Damon Runyon scientific community.
Congratulations to the six researchers named recipients of The Lasker Awards, among the most respected prizes in medicine. William G. Kaelin, Jr., MD (Damon Runyon Board Member, Chair of the Physician-Scientist Training Award Committee) of Dana-Farber Cancer Institute, Boston, received the Albert Lasker Basic Medical Research Award for his work to understand the pathway cells use to sense and adapt to changes in oxygen levels which led to the development of potential drugs for heart attack, stroke, and kidney cancer. Bruce M. Alberts, PhD (Former Fellowship Award Sponsor) of University of California, San Francisco, received the Lasker-Koshland Award for Special Achievement in Medical Science for his contributions to molecular biology and his advocacy for public science education.
Arvin C. Dar, PhD (Damon Runyon-Rachleff Innovator '14-'16) at the Icahn School of Medicine at Mount Sinai, reported that a “scaffolding protein” called the kinase suppressor of Ras (KSR) could be targeted as a way to disrupt signaling from mutant Ras protein. About 25 percent of human cancers have mutations in the Ras protein that disrupt growth signals and cause tumor development. The researchers tested over 170 compounds and discovered that one could effectively slow cancer growth. These findings lay a foundation for an entirely new class of drugs that, when used in combination with other therapies, could provide new effective treatment options for some of the hardest-to-treat cancers. The study was published in the journal Nature.
Colleen Delaney, MD, MSc (Damon Runyon Clinical Investigator ’07-’12) and colleagues at the Fred Hutchinson Cancer Research Center, Seattle, developed a method for using umbilical cord stem cells as a source of donor material for transplant. This is important because the majority of patients in need of a hematopoietic-cell transplant do not have a matched related donor. The advance is particularly valuable for minorities and people of mixed-race background. The researchers reported that in patients at high risk of relapse after transplant, cord blood transplant recipients seem to have better outcomes against leukemia and myelodysplastic syndrome. The study was published in The New England Journal of Medicine and featured in the Washington Post.
Amit J. Sabnis, MD (Damon Runyon-Sohn Pediatric Cancer Fellow ’13-’17), of the University of California, San Francisco, and colleagues, demonstrated that cancer cells co-opt a cellular “chaperone” protein called HSP70 (heat-shock protein 70) to promote their growth. By blocking that pathway, the scientists were able to kill cells derived from patients with rhabdomyosarcoma (RMS), a rare muscle-tissue cancer that affects children. The findings offer a potential new therapeutic pathway to fighting RMS, which is generally treatable in younger patients but can be fatal if diagnosed in older children after the disease has metastasized. The study was published in the Proceedings of the National Academy of Sciences.
Pavan Bachireddy, MD (Damon Runyon Physician-Scientist ’15-’19), Catherine J. Wu, MD (Damon Runyon-Lilly Clinical Investigator ’07-’12), and colleagues at the Dana-Farber Cancer Institute, Boston, reported that a new treatment approach, using repeated doses of the immunotherapy drug ipilimumab, may be able to restore a complete remission for some patients with advanced blood cancers that relapse after stem-cell transplant. In this Phase I study, 59 percent of patients receiving the highest dose of therapy (22 total) had a significant response ranging from complete remission to reduced tumor burden. This strategy could potentially prevent such relapses in the future. The study was published in the New England Journal of Medicine.
Daniel A. Heller, PhD (Damon Runyon Fellow ’10-’12), and colleagues at Memorial Sloan Kettering Cancer Center, New York, reported that radiation-guided nanoparticles may offer a new approach for penetrating the vascular barrier that often prevents current nanomedicines from reaching metastatic tumors. In a mouse model of lung cancer and metastatic melanoma and breast tumors, the nanoparticles selectively delivered chemotherapy drugs to the tumors. The researchers hope to translate these findings to clinical trials. The study was published in Science Translational Medicine.
Damon Runyon Clinical Investigators Aude G. Chapuis, MD (’15-’17) of Fred Hutchinson Cancer Research Center, Seattle, Cassian Yee, MD (’01-’06), of M.D. Anderson Cancer Center, Houston, Jedd D. Wolchok, MD, PhD (’03-’08), of Memorial Sloan Kettering Cancer Center, New York, and colleagues, have successfully treated a patient with metastatic melanoma by combining two different types of immunotherapy, harnessing the patient’s own immune system to attack and destroy the cancer. The first strategy isolated pure populations of the patient's immune T cells that can target the melanoma and then transferred them back into the patient. The other approach used an antibody to activate the patient's existing antitumor T cells by blocking the function of a protein called CTLA4, effectively releasing the “brakes” on the immune system. On their own, both treatments can slow the progression of metastatic melanoma, but they are rarely able to send the disease into complete remission. These physician-scientists combined the two immunotherapy approaches in a patient with metastasized melanoma who had previously shown little response to either treatment alone. Within weeks, the patient's tumors began to shrink, eventually disappearing completely. Over five years later, the patient remains disease free. This combination represents an encouraging strategy to induce long-term remission for metastatic melanoma. The study was published in The Journal of Experimental Medicine.
The Pershing Square Sohn Cancer Research Alliance has announced the winners of the 2016 Pershing Square Sohn Prize for Young Investigators in Cancer Research. The annual prize aims to catalyze collaboration among young investigators, academics, nonprofits, investors, and the biotech and pharmaceutical industries. The prize-winners will each receive funding for up to three years. Two of the seven awards were granted to Damon Runyon scientists:
Omar Abdel-Wahab, MD (Damon Runyon Clinical Investigator ’13-’16), Memorial Sloan Kettering Cancer Center, New York
Agnel Sfeir, PhD (Damon Runyon-Rachleff Innovator ’14-’16), NYU School of Medicine, New York
Election to the National Academy of Sciences is one of the highest honors that can be earned by a U.S. scientist. In recognition of their distinguished and continuing achievements in original biomedical research, members of the Damon Runyon community of scientists were inducted this May:
DAMON RUNYON FELLOWS
Adrian P. Bird, PhD (Damon Runyon Fellow '71-'73), Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, United Kingdom
Nathaniel Heintz, PhD (Damon Runyon Fellow '79-'81), The Rockefeller University, New York City
Philip A. Hieter, PhD (Damon Runyon Fellow '82-'84), University of British Columbia, Vancouver, Canada
DAMON RUNYON AWARD COMMITTEE MEMBERS
Kenneth W. Kinzler, PhD (Innovation Award Committee), The Ludwig Center at Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore
Amita Sehgal, PhD (Former Fellowship Award Committee), University of Pennsylvania, Philadelphia
Cameron J. Turtle, MD, PhD (Damon Runyon Clinical Investigator ’13-’16) and colleagues at the Fred Hutchinson Cancer Research Center, Seattle, successfully refined a cancer immunotherapy treatment, resulting in no detectable disease in 27 of 29 adult patients (93%) with B-cell acute lymphoblastic leukemia, or ALL. The pioneering technique uses two subsets of genetically engineered immune T-cells from the patient (CD19 CAR-T cells) to target and attack the cancer. The promising results were published in the Journal of Clinical Investigation.
Azad Bonni, MD, PhD (Damon Runyon Fellow ’96-’97) of Washington University School of Medicine, St. Louis, and colleagues, were the first to show that a protein called OSMR (Oncostatin M Receptor) is required for glioblastoma tumors to form. They found that blocking OSMR activity in brain tumor stem cells prevented them from forming tumors in mouse brains. In addition, an analysis of 339 tumor samples from human glioblastoma patients showed that higher OSMR expression corresponded with worse patient survival outcome. They plan to next develop small molecules or antibodies that can shut down the OSMR protein as a novel therapeutic strategy for treatment of glioblastoma. The study was published in Nature Neuroscience.
The American Association for Cancer Research (AACR) named several Damon Runyon scientists as 2016 recipients of its prestigious awards.
AACR Princess Takamatsu Memorial Lectureship: William G. Kaelin, Jr., MD (Damon Runyon Board Member, Chair of Clinical Investigator Award Committee), Dana-Farber Cancer Institute, Boston
AACR-CRI Lloyd J. Old Award in Cancer Immunology: Ronald Levy, MD (Damon Runyon Board Member, Innovation Award Committee Member), Stanford University, Stanford
AACR Award for Outstanding Achievement in Chemistry in Cancer Research: James Bradner, MD (Damon Runyon-Rachleff Innovator ’11-’13), Novartis Institutes for BioMedical Research, Cambridge
Ash Alizadeh, MD, PhD (Damon Runyon Clinical Investigator ’14-’17) and colleagues at Stanford University School of Medicine, Stanford, developed an enhanced technique that significantly increases the ability to accurately identify and sequence DNA from cancer cells circulating in a person’s blood. The technique, called “iDES-enhanced CAPP-Seq,” can be used to non-invasively identify tumor-specific mutations. The hope is that such “liquid biopsies” of easily obtained blood samples could eventually replace the need to surgically obtain tumor tissue for analysis. Their results were published in Nature Biotechnology.
Feng Zhang, PhD (Damon Runyon-Rachleff Innovator ‘12-‘14) of the Broad Institute, Cambridge, and Jennifer A. Doudna, PhD (Damon Runyon Fellowship Sponsor, Former Fellowship Award Committee Member) of the University of California, Berkeley, were announced as recipients of the prestigious Canada Gairdner International Award for 2016 "for development of CRISPR-CAS as a genome editing tool for eukaryotic cells.” They are among five scientists honored for pioneering accomplishments in this field.
Adam de la Zerda, PhD (Damon Runyon-Dale F. Frey Scientist ‘13, Damon Runyon Fellow ‘11-‘12) of Stanford University, Stanford, and colleagues, reported the success of a new technique called MOZART that enables 3D real-time imaging of individual cells or even molecules in a living animal. They were able to provide the first glimpse under the skin of a living animal, showing intricate details in the lymph and blood vessels. The technique could one day allow scientists to detect tumors at the earliest stage, to monitor how a tumor is responding to treatment, or to understand how individual cells break free from a tumor and travel to distant sites. The study was published in the journal Scientific Reports.
Douglas K. Graham, MD, PhD (Damon Runyon Clinical Investigator ’07-’12), of Emory University School of Medicine, Atlanta, and colleagues, reported that a novel compound called MRX-2843 has shown promise in preclinical studies; it blocked the growth of acute myeloid leukemia (AML) cells, led to a significant level of cancer cell death and more than doubled the median days of survival in laboratory models with a drug-resistant form of the disease. MRX-2843 is effective at targeting cancer cells with activated MERTK protein. They hope to obtain FDA approval to test the promising drug in adults and children with AML. The findings were published in the journal JCI Insight.
Andrew T. Chan, MD, MPH (Damon Runyon Clinical Investigator ‘08-‘13) of Harvard Medical School and Massachusetts General Hospital, Boston, and colleagues, reported an analysis of data from two long-term epidemiologic studies showing that regular use of aspirin significantly reduces the overall risk of cancer. Their findings suggest that the use of aspirin may complement, but not replace, the preventive benefits of colonoscopy and other methods of cancer screening. The study was published in JAMA Oncology and featured in The New York Times.
Gregory L. Beatty, MD, PhD (Nadia’s Gift Foundation Innovator ’12-’15) and colleagues at the Abramson Cancer Center at University of Pennsylvania, Philadelphia, reported the discovery of how macrophage immune cells can be “re-educated” by an experimental immune therapy (CD40 antibodies) to help break down the scaffolding that surrounds and protects pancreatic cancer from chemotherapy. They also identified a role for several factors, including chemokine ligand 2 (CCL2) and interferon gamma (IFN-g), that are released by the immune system after treatment with CD40 antibodies, and cooperate to redirect macrophages to attack cancer. The researchers are hopeful that their findings will spark further clinical interest. The study was published in the scientific journal Cancer Discovery.
Madhav Dhodapkar, MD (Damon Runyon-Lilly Clinical Investigator ‘02-‘07) of Yale Cancer Center, New Haven, and colleagues have determined that chronic stimulation of the immune system by lipids made in the context of inflammation underlies the origins of at least a third of all myelomas, a type of cancer affecting plasma cells. The study suggests that newer approaches to lower the levels of these lipids in patients with precursors for myeloma. Potentially, this could be achieved with drugs or lifestyle changes to reduce the levels of lipids to lower the risk of cancer. The findings were published in the New England Journal of Medicine.
Himisha Beltran, MD (Damon Runyon-Gordon Family Clinical Investigator ’13-’16) of Weill Cornell Medicine, New York, and colleagues, used next-generation sequencing technologies to analyze neuroendocrine prostate cancer, an aggressive resistant form of cancer which sometimes develops in certain patients. The researchers examined resistance in samples collected from 81 patients and discovered the distinctive genetic, epigenetic and molecular features that underlie neuroendocrine prostate cancer. Their findings may enable researchers to develop biomarkers to help identify this subset of patients with prostate cancer less likely to respond to the next line of hormonal-based therapies. In addition, this data may be used to develop new therapeutic approaches for patients. The study was published in the journal Nature Medicine.
Piero D. Dalerba, MD (Damon Runyon-Rachleff Innovator ‘16-‘17), of Columbia University Medical Center, New York, and colleagues, have identified a biomarker, the CDX2 gene, that could be used to predict which stage II colon cancer patients may benefit from chemotherapy after surgery to prevent a recurrence of their disease. They found that cancers that do not express the gene have a worse prognosis than those that do. The study was published in the online edition of the New England Journal of Medicine.
Mark A. Lemmon, PhD (Damon Runyon Scholar ’97-‘98, Damon Runyon Fellow ’93-’96) of Yale University, New Haven, and colleagues at The Children's Hospital of Philadelphia reported that a next-generation ALK inhibitor drug, called PF-06463922, shows promise in treating pediatric neuroblastoma. In animal models, it caused rapid and sustained tumor regression and was more effective than the FDA-approved ALK inhibitor crizotinib. This new drug is currently being tested in a phase 1/2 clinical trial of an ALK-driven subtype of lung cancer in adults. The researchers aim to pursue clinical development of this agent for treating children with an ALK-driven subtype of neuroblastoma. The study results were published in the journal Cancer Discovery.
David G. Kirsch, MD, PhD (Damon Runyon-Rachleff Innovator '08-'10, Innovation Award Committee Member) at the Duke University School of Medicine, Durham, and colleagues, have tested a new injectable agent that causes cancer cells in a tumor to fluoresce, potentially increasing a surgeon's ability to locate and remove all of a cancerous tumor on the first attempt. The study reports that in 15 patients undergoing surgery for soft-tissue sarcoma or breast cancer, the injectable agent called LUM015, identified cancerous tissue in human patients without adverse effects. The findings were published in Science Translational Medicine and featured in Time Magazine.