New Discoveries and Honors

Christine Iok In Chio, PhD (Damon Runyon Shirley Stein Fellow ‘13-‘17) of Cold Spring Harbor Laboratory, and colleagues, developed a 3D “organoid” culture system for pancreatic cancer that enables growth of pancreatic tissue not only from laboratory mouse models, but also from human patient tissue, offering a path to personalized treatment approaches in the future. The study was published in the journal Cell.

Lydia Finley, PhD (Damon Runyon Jack Sorrell Fellow ‘13-‘17) of Memorial Sloan Kettering Cancer Center, New York, and colleagues, demonstrated that stem cells can rewire their metabolism to enhance a mechanism that helps them avoid committing to a specific fate; in turn, this improves stem cells’ ability to renew themselves. She showed that the nutrients a stem cell uses, and how it uses them, can contribute to a cell’s fate by influencing gene expression through epigenetic modifications.

Peter D. Cole, MD (Damon Runyon-Sohn Pediatric Cancer Fellowship Award Committee, Damon Runyon Clinical Investigator ‘03-‘08) of Albert Einstein College of Medicine, Bronx, and colleagues, reported that common variations in four genes related to brain inflammation or cells’ response to damage from oxidation may contribute to the problems with memory, learning and other cognitive functions seen in children treated for acute lymphoblastic leukemia (ALL).

Catherine J. Wu, MD (Damon Runyon Clinical Investigator ‘07-‘12) and colleagues at Dana-Farber Cancer Institute, Boston, found that in patients with chronic lymphocytic leukemia (CLL), treatment produced shorter remissions if the tumor tissue showed signs of highly disorganized methylation, chemical modifications on the DNA that regulate gene expression. The findings demonstrate that such disorganization can actually benefit tumors and render them less vulnerable to anti-cancer drugs.

John M. Timmerman, MD (Damon Runyon Clinical Investigator ‘05-‘10) of University of California, Los Angeles, Gordon J.

Jedd D. Wolchok, MD, PhD (Damon Runyon-Lilly Clinical Investigator ‘03-‘08) and colleagues at Memorial Sloan Kettering Cancer Center, New York, reported a key discovery that explains why some patients respond to Yervoy/ipilimumab, an immunotherapy drug, while others do not. They found that the cancer cells from patients who respond to the drug carry a high number of genetic mutations—some of which make tumors more visible to the immune system, and therefore easier to fight.

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, members of the Damon Runyon Cancer Research Foundation community were inducted this month:

Feng Zhang, PhD (Damon Runyon-Rachleff Innovator ‘12-‘14) of the Broad Institute and Massachusetts Institute of Technology, Cambridge, is one of six promising early career scientists named as 2014 NYSCF-Robertson Stem Cell Investigators. The award is designed to support scientists engaged in novel neuroscience and cutting-edge translational stem cell research. Each Investigator will receive a generous five-year award.

Matthew G. Vander Heiden, MD, PhD (Damon Runyon-Rachleff Innovator ‘11-‘13, Damon Runyon Fellow ‘06-‘08) of MIT, Cambridge, and colleagues, reported the discovery of a sign of the early development of pancreatic cancer – an increase in certain amino acids due to changes in metabolism. This occurs before the disease is diagnosed and symptoms appear, and the researchers hope that eventually they may be able to use this information to detect the disease earlier.

Sidi Chen, PhD (Damon Runyon Fellow ‘12-‘15) and Feng Zhang, PhD (Damon Runyon-Rachleff Innovator ‘12-‘14) of the Broad Institute and Massachusetts Institute of Technology, Cambridge, developed a new mouse model that allows scientists to use the CRISPR-Cas9 system for in vivo genome editing experiments. They demonstrated the utility of the new “Cas9 mouse” model to edit multiple genes in a variety of cell types, and to model lung adenocarcinoma.

Bradley L. Pentelute, PhD (Damon Runyon-Rachleff Innovator '13-'15), and colleagues at Massachusetts Institute of Technology, Cambridge, used a disarmed version of the anthrax toxin to deliver two proteins known as antibody mimics, which can kill cancer cells by disrupting specific proteins inside the cells. In this study, they successfully targeted Bcr-Abl and hRaf-1, which both have known functions in cancer.

Zefeng Wang (Damon Runyon Fellow '03-'06) of UNC School of Medicine, Chapel Hill, discovered that a protein crucial to the process of gene splicing, called RBM4, is drastically decreased in multiple forms of human cancer, including lung and breast cancers. This reduction in RBM4 results in altered gene expression, giving rise to cancer development and metastasis. Components of the splicing pathway could be potential targets for new cancer therapies. The study was published in the journal Cancer Cell.

Moritz F. Kircher, MD, PhD (Damon Runyon-Rachleff Innovator ‘14-‘16) and colleagues at Memorial Sloan Kettering Cancer Center, New York, developed a new handheld device (“Raman scanner”) that can accurately detect cancer cells during surgery. The device resembles a laser pointer and detects nanoprobes that mark tumor cells but not normal cells. In a mouse model of glioblastoma, the scanner enabled researchers to successfully identify and remove all malignant cells in the animals’ brains.

Emily P. Balskus, PhD (Damon Runyon-Rachleff Innovator ‘14-‘16) of Harvard University, Cambridge, has been named to MIT Technology Review’s list of “35 Innovators under 35” for her research focused on how gut bacteria use chemical reactions to survive. The list is comprised of “exceptionally talented technologists whose work has great potential to transform the world.”

Ian Y. Wong, PhD (Damon Runyon Fellow ‘10-‘13) of Brown University, Providence, and colleagues, developed a microchip that enabled cancer cells to be imaged as they migrated across a surface that mimics the tissue surrounding a tumor. They examined cells that had undergone epithelial-mesenchymal transition (EMT), a process in which epithelial cells that stick together within a tissue, change into mesenchymal cells that can disperse and migrate individually.

Gordon J. Freeman, PhD (Damon Runyon Fellow ‘79-‘81), of Harvard Medical School and Dana-Farber Cancer Institute, Boston, was named one of four recipients of the 2014 William B. Coley Award for Distinguished Research in Tumor Immunology. He is recognized for his contributions to the discovery of the programmed cell death-1 (PD-1) receptor pathway, a new immune system checkpoint that has been shown in clinical studies to be a highly promising target in cancer immunotherapy.

Nicholas E. Navin, PhD (Nadia’s Gift Foundation Damon Runyon-Rachleff Innovator '13-'15) and colleagues at M.D. Anderson Cancer Center, Houston, developed a single cell sequencing tool (NUC-SEQ) that can measure genome-wide mutations in individual cancer cells. This study revealed that different subtypes of breast cancer have varied tumor diversity, and that different tumor cells grow at dramatically different speeds. These findings may have important implications for the diagnosis and treatment of breast cancer.

Matthew L. Meyerson, MD, PhD (Damon Runyon Fellow ‘95-‘98) of Dana-Farber Cancer Institute and the Broad Institute, Cambridge, led a recent study by the NIH Cancer Genome Atlas project, which represents the most comprehensive genomic analysis of lung adenocarcinoma, a cancer that forms in the tissues near the outer parts of the lungs. Researchers identified 18 key mutations in an analysis of 230 patient lung tumors.

Andrew L. Feldman, MD (Damon Runyon Clinical Investigator ‘09-‘14), and colleagues at the Mayo Clinic, Rochester, reported that novel genetic tests can be used to determine the best treatment options for patients with anaplastic large-cell lymphoma (ALCL), a rare type of non-Hodgkin lymphoma. There are three subgroups of ALCL that have very different survival rates.

Jedd D. Wolchok, MD, PhD (Damon Runyon-Lilly Clinical Investigator ‘03-‘08) at Memorial Sloan Kettering Cancer Center, New York, and colleagues, reported the results of an ongoing clinical trial evaluating the safety and activity of combined immunotherapies for treatment of advanced melanoma. Nivolumab (anti-PD-1), an investigational PD-1 immune checkpoint inhibitor, and ipilimumab (anti-CTLA-4; Yervoy), were given either concurrently or sequentially to these patients. The two-year overall survival rate was 88%.

Eranthie Weerapana, PhD (Damon Runyon-Rachleff Innovator ‘12-‘14) and colleagues at Boston College, Chestnut Hill, have developed new nanotechnology “cage” that can entrap small molecule drugs and infiltrate cancer cells. This is a promising drug delivery system that could be used to fight cancer and other diseases. The results were published in the American Chemical Society journal ACSNano.

Andrew T. Chan, MD, MPH (Damon Runyon Clinical Investigator ‘08-‘13) of Massachusetts General Hospital, Boston, working with a multi-institutional team, analyzed data from two long-term studies involving nearly 128,000 participants. The researchers found that individuals whose colons have high levels of a specific gene, 15-hydroxyprostaglandin dehydrogenase (15-PGDH), dramatically reduce their chances of developing colorectal cancer by taking aspirin.

Madhav Dhodapkar, MD (Damon Runyon-Lilly Clinical Investigator ‘02-‘07), Yale Cancer Center, New Haven, reported positive results from a Phase 1 clinical trial using a cancer vaccine called CDX-1401, which activates the patient’s immune system against cancers that express the tumor marker NY-ESO-1. In 45 patients with advanced malignancies (melanoma or non-small cell lung cancer), thirteen patients experienced stabilization of disease and two patients had tumor regression.

Feng Zhang, PhD (Damon Runyon-Rachleff Innovator ‘12-‘14), of the Broad Institute, Cambridge, was named the 2014 recipient of its Alan T. Waterman Award from the National Science Foundation (NSF). This award is NSF’s highest honor that recognizes an outstanding researcher under the age of 35 and funds his or her research in any field of science or engineering.

Sean Bendall, PhD (Damon Runyon-Dale F. Frey Scientist ‘14-‘16, Damon Runyon Fellow ‘09-‘12), of Stanford University, Stanford, and colleagues, reported the development of a new technology that can simultaneously detect as many as 100 clinically important proteins in breast tumor cells-conventional methods can pinpoint only two to four at the same time.

Clark C. Chen, MD, PhD (Damon Runyon Fellow ‘04-‘06) of the University of California, San Diego School of Medicine, La Jolla, and colleagues,  reported that FDA-approved anti-psychotic drugs possess tumor-killing activity against the most aggressive form of brain cancer, glioblastoma.

Dmitriy Zamarin, MD, PhD (Dr. Bart A. Kamen Fellow ‘13-‘15) in the laboratory of Jedd D. Wolchok, MD, PhD (Damon Runyon-Lilly Clinical Investigator ‘03-‘08) at Memorial Sloan Kettering Cancer Center, New York, reported the clinical efficacy of a combined approach using checkpoint blockade, a strategy that harnesses the immune response to treat cancers, and oncolytic virotherapy, an investigational intervention that uses viruses to destroy tumors.

The American Association for Cancer Research (AACR) named two Damon Runyon alumni as 2014 recipients of its prestigious awards. Elaine V.

Renier J. Brentjens, MD, PhD (Damon Runyon-Lilly Clinical Investigator ‘06-‘11) and colleagues at the Memorial Sloan-Kettering Cancer Center, New York, reported the success of immunotherapy treatment in adults with acute lymphoblastic leukemia (ALL). This is the largest clinical study conducted thus far; it showed that 88 percent of patients achieved complete remissions after being treated with their own T immune cells, which had been genetically modified to target and attack the cancer cells.

William Y. Kim, MD (Damon Runyon-Merck Clinical Investigator ‘09-‘14) of University of North Carolina Lineberger Cancer Center, Chapel Hill, and colleagues, reported the results of a comprehensive genetic analysis of 262 invasive bladder cancer tumors. The researchers found that the disease shares genetic similarities with two forms of breast cancer, basal-like and luminal. They hope that the identification of these subtypes will lead to improved diagnosis as well as effective targeted therapies for bladder cancer.

Jean Y. Tang, MD, PhD (Damon Runyon Clinical Investigator ‘11-‘14) of Stanford University School of Medicine, Stanford, and colleagues, reported that a common inexpensive anti-fungal drug, called itraconazole, may be useful in treating basal cell carcinoma (the most common form of skin cancer). The drug was tested in a Phase II clinical trial with 29 patients who had a total of 101 tumors. Within a month, the size and spread of tumors had decreased in most patients.

Pardis C. Sabeti, MD, PhD (Damon Runyon Fellow ‘04-‘06), Harvard University, Cambridge, was named one of three recipients of the 2014 Vilcek Prize for Creative Promise in Biomedical Science.  The awards from the Vilcek Foundation recognize young foreign-born biomedical scientists, 38 years old or younger, who demonstrate outstanding early achievement.

Adam de la Zerda, PhD (Dale F. Frey Scientist ‘13, Damon Runyon Fellow ‘11-‘12) of Stanford University, Stanford, was named to the Forbes Magazine “30 Under 30” list in Science and Healthcare for 2014. Adam is using sound waves to image the body at the molecular level, applying the technology to take pictures of brain tumors, blood, and living mice. Those on this list are described as the “brightest young stars” of their generation.