The Damon Runyon Cancer Research Foundation named seven new Damon Runyon Clinical Investigators at its spring 2014 Clinical Investigator Award Committee review. The recipients of this prestigious three-year award are outstanding early career physician-scientists conducting patient-oriented cancer research at major research centers under the mentorship of the nation’s leading scientists and clinicians. Each will receive $450,000 to support the development of his/her cancer research program.
The Foundation also awarded Continuation Grants to three Damon Runyon Clinical Investigators. Each award will provide an additional two years of funding totaling $300,000. The Continuation Grant is designed to support Clinical Investigators who are approaching the end of their original awards and need extra time and funding to complete a promising avenue of research or clinical trial. This program is possible through the generous support of the William K. Bowes, Jr. Foundation, and Connie and Robert Lurie.
The Clinical Investigator Award program is specifically intended to help address the shortage of physicians capable of translating scientific discovery into new breakthroughs for cancer patients. In partnerships with industry sponsors and through its new Accelerating Cancer Cures initiative, the Damon Runyon Cancer Research Foundation has committed nearly $49 million to support the careers of 77 physician-scientists across the United States since 2000.
2014 Clinical Investigator Awardees
Arash Ash Alizadeh, MD, PhD
Diffuse Large B-cell Lymphoma (DLBCL) is the most common aggressive lymphoma in adults. Unfortunately, current therapies typically fail in nearly half of these patients. Dr. Alizadeh proposes a novel treatment strategy for this disease: to characterize and isolate premalignant stem cells before they transform into cancer cells. He has found that expression of a single oncogene called BCL6 is capable of reprogramming these cells from normal cells to aggressive malignant cells. He aims to define the specific genetic alterations that can give rise to this cell reprogramming. This research will be important both for understanding cancer biology, as well as for developing more effective means for treatment of lymphoma patients.
Dr. Alizadeh works under the mentorship of Ronald Levy, MD, at the Stanford University School of Medicine, Stanford, California.
Joshua Brody, MD
Dr. Brody aims to develop a novel treatment approach for patients with advanced-stage lymphoma, by which the patient’s immune system is trained to recognize and eliminate his/her own cancer. This approach, an “in situ vaccine,” recruits and activates specific immune cells, dendritic cells (DC), at the location of the treated tumor—where they can then educate the rest of the immune system to recognize and eliminate tumors throughout the body. The first patients enrolled on this clinical trial have already shown the recruitment and activation of DC within the treated tumor as well as regressions of lymphoma at sites distant from the treated site. The in situ vaccine will initially be tested in patients with low-grade lymphoma, with the goal of quickly expanding to other tumor types including melanoma and head and neck cancer.
Dr. Brody works under the mentorship of Nina Bhardwaj, MD, PhD, and Miriam Merad, MD, PhD, at The Icahn School of Medicine at Mount Sinai Hospital, New York, New York.
Lihua Elizabeth Budde, MD, PhD
Hematopoietic stem cell transplant is the preferred and only curative treatment for most patients with acute myeloid leukemia (AML); however, a significant percentage of patients will eventually relapse. A novel effective therapy option is therefore urgently needed. Dr. Budde is testing a new strategy that uses patients’ own immune T cells, which have been modified to specifically target and kill leukemia cells. She will direct a Phase 1 clinical trial using these modified immune T cells as therapeutics for patients with AML. She is also developing ways to enhance the potency of these modified immune cells in killing leukemia cells. This therapeutic approach has the potential to change the treatment paradigm and may significantly improve the cure rate for patients with leukemia.
Dr. Budde works under the mentorship of Stephen J. Forman, MD, FACP, at City of Hope, Duarte, California.
Alejandro Gutierrez, MD
It remains unclear why some patients’ tumors can be cured with chemotherapy, whereas other tumors that appear to be nearly identical are completely chemoresistant. Dr. Gutierrez focuses on this issue in a particularly high-risk subset of T-cell acute lymphoblastic leukemia, a disease that most commonly affects older children and young adults. His goals are to define the molecular basis of resistance to conventional chemotherapy in patients with this disease, and to leverage this knowledge to develop a therapeutic strategy to restore chemosensitivity. Ultimately, this could lead to significant improvements in clinical outcome for these patients.
Dr. Gutierrez works under the mentorship of Stuart H. Orkin, MD, and Anthony Letai, MD, PhD, at Boston Children’s Hospital, Boston, Massachusetts.
Peter S. Hammerman, MD, PhD
Despite the initial success of targeted therapies for cancer, these treatments have limited efficacy in most diseases. Recent studies have shown that the immune cells that infiltrate a tumor play an active role in dictating the response to therapy; specific new therapies can augment the ability of the immune system to fight a cancer in combination with conventional therapies. Dr. Hammerman is using lung cancer as a model to explore genome-scale approaches to dissect this complex relationship between the tumor and its immune microenvironment. The goal of this research is to better define the optimal types of therapy for lung cancer by combining drugs that target the genetic alterations found in the tumor with those aimed at enhancing the immune response to the cancer, and to translate these findings into clinical practice.
Dr. Hammerman works under the mentorship of Glenn Dranoff, MD, Stephen F. Hodi, MD, and Kwok-Kin Wong, MD, PhD, at Dana-Farber Cancer Institute, Boston, Massachusetts.
Luc G.T. Morris, MD
Head and neck cancer is a lethal malignancy that can arise in the mouth, throat, voice box, and related areas. These tumors are squamous cell cancers that are, in many cases, caused by tobacco use or human papillomavirus (HPV) infection. Head and neck cancers have many molecular similarities with squamous cell cancers of the lung and esophagus. Dr. Morris is studying a poorly understood gene called FAT1, which is frequently altered in head and neck cancer (as well as lung and esophageal cancer). He has found that this gene, in its normal state, prevents tumor development. In this project, he will determine the effects of FAT1 alterations on tumor cell growth and the clinical prognosis of patients. This work will help to develop new ways of therapeutically targeting the pathways that promote the development of head and neck and other squamous cell cancers.
Dr. Morris works under the mentorship of Timothy Chan, MD, PhD, and James A. Fagin, MD, at Memorial Sloan Kettering Cancer Center, New York, New York.
Stephen T. Oh, MD, PhD [Doris Duke-Damon Runyon Clinical Investigator]
Myeloproliferative neoplasms (MPNs) are a group of blood cancers in which a malignant cell population proliferates out of control. Myelofibrosis (MF) is one type of MPN in which the bone marrow becomes replaced by scar tissue, leading to progressive failure of normal blood cell functions and ultimately death, on average five years after initial diagnosis. MPNs, including MF, can evolve to secondary acute myeloid leukemia (sAML), which is almost invariably fatal. There is no reliable curative treatment currently available for MPNs or MF. Targeted inhibitors of a protein called JAK2 provide significant symptomatic benefit for MF patients. However, these treatments do not cure the disease, nor has it been shown that they can prevent or delay progression to sAML. Dr. Oh aims to investigate the cellular abnormalities that underlie these blood cancers. These studies have the potential to lead to the development of improved treatments for MPNs.
Dr. Oh works under the mentorship of Daniel Link, MD, at Washington University, St. Louis, Missouri.
2014 Clinical Investigator Continuation Grants
Marie Bleakley, MD [Richard Lumsden Foundation Investigator]
Bone marrow transplantation, or allogeneic hematopoietic stem cell transplant (HCT), is the only curative therapy for many patients with leukemia. Certain immune cells, called T cells, contained in the donor HCT graft can cause a “graft versus leukemia” (GVL) effect which eliminates leukemic cells. Unfortunately, there are also donor T cells in the HCT graft that can cause a condition called “graft versus host disease” (GVHD). GVHD is a life-threatening immune response that remains the major barrier to the success of transplantation. Dr. Bleakley is developing new approaches to separate the beneficial GVL effect from detrimental GVHD after bone marrow transplantation. She has identified specific subsets of immune cells that promote GVHD; these cells can then be eliminated to reduce the frequency or severity of GVHD, while at the same time maintaining and improving the GVL effect. The Continuation Grant will be used to move this study to the clinical trial phase.
Dr. Bleakley works under the mentorship of Stanley R. Riddell, MD, at the Fred Hutchinson Cancer Research Center, Seattle, Washington.
Zsofia K. Stadler, MD
Dr. Stadler is a clinical geneticist whose research goal is to determine the genetic basis of “sporadic” cancers in young adults. She is testing the hypothesis that de novo (spontaneous) chromosomal changes in the genome are associated with testicular germline cancer. The Continuation Grant will be used to apply high-resolution sequencing technology to compare the whole genomes of patients to those of their parents, with the goal of identifying rare genetic variants associated with cancer susceptibility and risk. This approach represents a new paradigm in cancer genetics, which could have broad applications in terms of cancer risk stratification and cancer prevention.
Dr. Stadler works under the mentorship of Kenneth Offit, MD, MPH, and Michael H. Wigler, PhD, at Memorial Sloan Kettering Cancer Center, New York, New York.
Jean Y. Tang, MD, PhD
Basal cell carcinoma (BCC) is the most common type of skin cancer. Mutations in the Hedgehog (HH) signaling pathway are frequently found in these cancers. Early-stage clinical studies of a HH pathway inhibitor drug have been successful, with 55% of patients reported to respond. However, most tumors develop drug resistance during the course of therapy. Dr. Tang has characterized mechanisms of drug resistance and is working to identify new drug combinations that are effective in treatment of BCC. The Continuation Grant will enable her to move her findings on resistance to clinical trials in patients. Her studies have the potential to benefit patients with BCC as well as those with other HH-dependent cancers, such as medulloblastoma.
Dr. Tang works under the mentorship of Philip A. Beachy, PhD, and Ervin H. Epstein, MD, at Stanford University, Stanford, California.
DAMON RUNYON CANCER RESEARCH FOUNDATION
To accelerate breakthroughs, the Damon Runyon Cancer Research Foundation provides today’s best young scientists with funding to pursue innovative research. The Foundation has gained worldwide prominence in cancer research by identifying outstanding researchers and physician-scientists. Twelve scientists supported by the Foundation have received the Nobel Prize, seven others have received National Medals of Science, and 65 have been elected to the National Academy of Sciences. Since its founding in 1946, Damon Runyon has invested nearly $275 million and funded more than 3,420 young scientists.
100% of all donations to the Foundation are used to support cutting-edge scientific research. Its administrative and fundraising costs are paid from its Damon Runyon Broadway Tickets and endowment.
For more information, visit http://www.damonrunyon.org.
Outlet Full Name: Eurekalert
Author: Yung S. Lie, Ph.D.