New York, NY, July 1, 2013 — The Damon Runyon Cancer Research Foundation named six new Damon Runyon Clinical Investigators at its spring 2013 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 initiate/continue a 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 almost $45 million to support the careers of 70 physician-scientists across the United States since 2000.
2013 Clinical Investigator Awardees
Omar Abdel-Wahab, MD
Dr. Abdel-Wahab specializes in specific blood cancers called myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML). He recently identified mutations in the gene ASXL1 in patients with MDS and AML. ASXL1 is one of the most commonly mutated genes in MDS patients, and these mutations occur in up to 20% of AML patients. ASXL1 mutations result in a worsened overall survival in MDS and AML patients and contribute to chemotherapy resistance in AML. However, exactly how these mutations contribute to leukemia development remains unknown.
He has demonstrated that loss of ASXL1 results in increased expression of genes that are known to promote development of AML. Preliminary data suggests that ASXL1 regulates expression of key genes by affecting proteins called histones. In a mouse model, loss of ASXL1 alone results in a phenotype remarkably similar to human MDS. Moreover, when ASXL1 loss is combined with other genes known to promote chronic leukemia in mice, an acute leukemia develops that hastens death of the mice. His overall goal is to gain a more thorough understanding of ASXL1 function and to ultimately test approved as well as novel targeted therapeutics for treatment of MDS and AML.
Dr. Abdel-Wahab works under the mentorship of Ross L. Levine, MD, at Memorial Sloan-Kettering Cancer Center, New York, New York.
Himisha Beltran, MD [Damon Runyon-Gordon Family Clinical Investigator]
Many prostate cancers initially respond to treatments that block the hormone testosterone, thus halting tumor growth. These treatments block testosterone by targeting a molecule called the androgen receptor (AR). However, patients often develop resistance to these drugs, giving rise to an aggressive AR-independent form of prostate cancer. Often under-recognized, AR-negative neuroendocrine prostate cancer (NEPC) currently represents approximately 25% of advanced prostate cancers. The clinical diagnosis is most often made when the cancer has metastasized, especially to liver and brain, and is associated with a low prostate specific antigen (PSA) level. The poor prognosis of NEPC is, in part, due to an incomplete understanding of the molecular events underlying its development.
By utilizing valuable tissue resources and state-of-the-art technologies, Dr. Beltran seeks to comprehensively evaluate NEPC tumors for recurrent molecular alterations and determine their functional and clinical impact. She will identify a genomic profile that distinguishes NEPC from the more common type of prostate cancer, prostate adenocarcinoma, and evaluate the impact of NEPC-associated alterations on patient outcomes and their ability to predict patient response to available therapies. Her goal is to improve our understanding of molecular events associated with disease progression and help develop strategies toward preventing NEPC. Distinguishing NEPC will help identify prostate cancer patients unlikely to benefit from additional AR-targeted strategies and select patients for novel targeted treatment approaches for NEPC.
Dr. Beltran works under the mentorship of Mark A. Rubin, MD, at Weill Medical College of Cornell University, New York, New York.
Christine M. Lovly, MD, PhD
Lung cancer is responsible for more cancer-related deaths in the U.S. and worldwide each year than any other cancer. Historically, patients with advanced metastatic disease have been treated with conventional chemotherapy. Recently, however, subsets of lung cancer patients have been identified with specific molecular alterations that allow for treatment with rationally chosen targeted therapies. One molecular subset of lung cancer is characterized by the presence of alterations in a protein called ALK tyrosine kinase. Patients with lung cancers that harbor ALK fusions derive significant clinical benefit from a newly approved drug that blocks the action of the mutant ALK. Unfortunately, the degree and duration of tumor response to ALK inhibitor drugs varies, and patients inevitably develop progressive disease, or "acquired resistance." Additional strategies are needed to improve the treatment of these lung cancer patients.
Dr. Lovly's goal is to develop novel treatment strategies for ALK positive lung cancer.
She plans to improve our understanding of how ALK fusions transmit signals to promote cancer and of how these signals become altered in the context of acquired resistance to ALK inhibitors. Her work will identify novel targets that can be blocked in combination with ALK inhibitors, to promote enhanced anti-tumor responses. Since ALK mutations have been described in a growing number of hematologic and solid organ tumors, an improved understanding of ALK signaling—as well as mechanisms of resistance to ALK inhibition—may also have potential implications for other cancers.
Dr. Lovly works under the mentorship of William Pao, MD, PhD, at Vanderbilt University School of Medicine, Nashville, Tennessee.
Ann Mullally, MD
Myeloproliferative neoplasms (MPN) are a type of blood cancer sometimes considered to be "pre-leukemias" which can progress to leukemia and are also lethal cancers in their own right. A population of rare hematopoietic stem cells (HSC), called MPN disease-propagating cells, typically harbor mutations that cause the cells to overproliferate. These mutated HSC produce abnormal cancerous blood cells that over time can eliminate the normal blood cells in the bone marrow. In MPN, the cancerous blood cells secrete an excess of substances called growth factors that allow cancer cells to survive.
Dr. Mullally aims to understand which of the growth factors help the mutated HSC to survive and to then use drugs to block the activity of these growth factors, thus killing the mutated HSC. This approach will lead to more successful treatments for MPN and leukemia, resulting in a higher cure rate for patients.
Dr. Mullally works under the mentorship of Benjamin L. Ebert, MD, and Daniel J. Deangelo, MD, PhD, at Brigham and Women's Hospital, Boston, Massachusetts.
Deepak Nijhawan, MD, PhD
Despite recent advances, lung cancer remains the leading cause of cancer related death in the United States, and there is an urgent need for new therapies. The most successful treatments for lung cancer to date are the targeted drugs erlotinib and crizotinib. These drugs block tumor growth in cancers that respectively harbor either mutations in EGFR or translocations in the ALK gene. Unfortunately, only a minor fraction of patients' tumors have EGFR mutations or ALK translocations; therefore, the vast majority of patients lack an effective targeted therapy.
Dr. Nijhawan aims to identify novel targets in lung cancer so that similarly effective therapy can be developed for other patients. He has identified a set of chemicals called benzothiazoles that are effective in blocking the growth of 25% of lung cancer cell types tested. The protein target of the benzothiazole and the genetic alterations that predict sensitivity are unknown. His research focuses on identifying both the benzothiazole protein target as well as predictive biomarkers that explain why only certain lung cancers are susceptible to its effect. The identification of these biomarkers in lung cancer patients may highlight a set of patients who could be treated with benzothiazole-related compounds.
Dr. Nijhawan works under the mentorship of Steve L. McKnight, PhD, and David Johnson, MD, at UT Southwestern Medical Center, Dallas, Texas.
Cameron J. Turtle, MD, PhD
Hematopoietic stem cell transplantation (HCT) is a potentially curative procedure for patients with hematologic malignancies who are otherwise incurable with conventional therapies. Despite advances in post-transplant care, the morbidity and mortality of complications such as graft versus host disease (GVHD) and infections remain significant limitations, and hinder the application of this life-saving procedure. Infection and GVHD are influenced by the immune system, which in turn is regulated by the bacterial contents of the human gastrointestinal tract.
Dr. Turtle will test the hypotheses that alterations in the bacterial composition of the human gastrointestinal tract regulate the reconstitution of a specialized bacteria-responsive subset of immune cells after HCT, and that impaired regulation of this immune cell subset is associated with an increased risk of infection or GVHD.
Dr. Turtle works under the mentorship of Stanley R. Riddell, MD, at Fred Hutchinson Cancer Research Center, Seattle, Washington.
2013 Clinical Investigator Continuation Grants
Tobias Carling, MD, PhD
Dr. Carling focuses on endocrine tumors, a type of cancer that affects hormone-producing tissues in the body (such as the thyroid, pituitary gland, adrenal gland and islet cells of the pancreas). The underlying genetic basis for endocrine tumors is not yet known. Dr. Carling's goal is to complete a comprehensive genomic analysis of patients with endocrine tumor disease in order to identify individual genes involved in early cancer formation. The Continuation Grant will be used to further these studies on endocrine tumors and also characterize thyroid and adrenal cancers. He aims to use these findings to develop improved strategies for personalized medical and surgical treatment of cancer patients.
Dr. Carling works under the mentorship of Richard P. Lifton, MD, PhD, and Robert Udelsman, MD, MBA, at Yale University School of Medicine, New Haven, Connecticut.
N. Lynn Henry, MD, PhD
Due to advances in cancer screening and treatments, the majority of women diagnosed with breast cancer will be cured of their disease. However, many will require at least five years of therapy with medications called aromatase inhibitors, which greatly reduce the amount of estrogen circulating in the body. These drugs cause new or worsening aches and pains in about half of women taking them, resulting in decreased quality of life.
The overall goal of this project is to obtain a better understanding of why some patients with breast cancer develop treatment-related pain. Dr. Henry [Damon Runyon-Lilly Clinical Investigator] will use the Continuation Grant to investigate the impact of chemotherapy on pain processing pathways, which could predispose patients to chronic pain. She will also evaluate factors that could be used to predict which patients with aromatase inhibitor-associated pain will respond to a specific type of therapy called duloxetine. A greater understanding of why breast cancer survivors develop treatment-related pain could lead to prevention or better management of symptoms, thereby improving long-term quality of life.
Dr. Henry works under the mentorship of Daniel F. Hayes, MD, at the University of Michigan, Ann Arbor, Michigan.
Brian G. Till, MD
Certain types of lymphoma, such as the indolent B cell lymphomas and mantle cell lymphoma, are incurable with standard therapies. These diseases can, however, be cured using stem cell transplantation, in which immune T cells from the donor kill lymphoma cells. This procedure unfortunately carries the serious risk of graft-versus-host disease, which can be life-threatening.
In order to provide safer therapy options, Dr. Till [Damon Runyon-Pfizer Clinical Investigator] aims to develop a new treatment for lymphoma using patients' own T cells to fight their cancers: patient cells are collected, a gene is inserted into the cells that allows them to recognize and kill lymphoma cells, and then the cells are infused back into the patient. Using his Continuation Grant, he is leading a phase I clinical trial testing this treatment in lymphoma patients. He is optimistic that this strategy will translate into a safe, curative treatment for patients with lymphoma; insights from this work may help to advance similar treatments for other types of cancer.
Dr. Till works under the mentorship of Oliver W. Press, MD, PhD, at the Fred Hutchinson Cancer Center, Seattle, Washington.
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. Eleven 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 $270 million and funded more than 3,400 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.
Yung S. Lie, PhD
Chief Scientific Officer
Damon Runyon Cancer Research Foundation
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