ST. LOUIS (June 26, 2015) – Pedal the Cause is pleased to announce the awarding of five new cancer research grants. These grant awards were made possible by the tremendous support of the 2014 Pedal the Cause participants who helped raise $2.76 million to accelerate lifesaving cancer research at Siteman Caner Center and St. Louis Children's Hospital. Pedal the Cause has now funded 57 cancer research projects in St. Louis — including 42 adult and 15 pediatric projects. The five new cancer research projects were awarded through Siteman Cancer Center's new Siteman Investment Program.
“While we are always excited to provide funding for the most innovative and promising cancer research projects, we are even more delighted that this program serves as a catalyst for new discoveries by fostering St. Louis' vital, collegial research community,” stated Jay Indovino, executive director of Pedal the Cause. “We look forward to learning more about these new advances in cancer research and how they will translate into groundbreaking, practical applications.”
Four of the five newly-funded projects are led by principal investigators at Washington University School of Medicine in St. Louis, while the other project is led by a principal investigator who is a St. Louis University School of Medicine consortium faculty member of Siteman Cancer Center.
With the bold model of using 100% of public donations to fund world-class cancer research, Pedal the Cause has quickly become the gateway to curing cancer — all cancers, for everyone. Pedal the Cause, a community-wide cycling event that raises funds to advance cancer research at Siteman Cancer Center and St. Louis Children's Hospital, has donated an astounding $9.36 million in merely five years — 100% of which went directly to supporting innovative cancer research in St. Louis.
“So far, Pedal the Cause-funded projects have leveraged this support at a rate of 9 to 1. That means for every $1 from Pedal the Cause, an additional $9 is obtained from other sources like the National Institutes of Health,” said Indovino. “Support from Pedal the Cause continues to increase, as does the rate at which this funding is leveraged. With a goal of donating an additional $20–$30 million in the next five years, Pedal the Cause hopes to make an even greater impact of about $300 million, for a 10-year local impact of close to $400 million.”
Join the movement: Take advantage of the Early Bird Special by registering for Pedal the Cause by July 1 and save 50% on your fundraising minimum. Pedal the Cause will take place on Sept. 26 & 27, 2015, at the Chesterfield Amphitheater in Chesterfield, Mo. Visit stlouis.pedalthecause.org
for more information or to make a donation toward a world without cancer.
About the Newly-Funded Research Projects:
Project: Targeting Focal Adhesion Kinase to Render Pancreatic Cancer Responsive to Immunotherapy
Principal Investigator: David G. DeNardo, Ph.D., Washington University School of Medicine in St. Louis
The prognosis for patients with pancreatic cancer (PaC) is dismal, with a 5-year survival rate of less than 6%. This is due to the propensity of PaC to metastasize early and to the very poor effectiveness of our best cytotoxic therapies. Thus, the development of new treatment strategies is critical for this disease. This makes PaC an attractive target for immunotherapy. However, attempts to date have failed to deliver strong clinical results. The consensus is that resistance to both cytotoxic and immunotherapies is due to the unique tumor microenvironment present in PaC. One of the major features of the PaC microenvironment is the presence of high levels of fibrosis. This fibrotic microenvironment is reminiscent of scar tissue in a healing wound. Normal fibrotic scar tissue provides a structural and cellular barrier to invading organisms, while allowing the healing process to proceed without the immune system attacking the healing tissue. Similarly in PaC, this scar-like microenvironment has proven to be a barrier to the delivery of cytotoxic therapy and effective immunotherapy. As such, direct targeting of fibrosis has been the focus of many studies; however, as part of normal wound healing, this approach is not without significant potential toxicity. As an alternative approach, we propose to target the tumor cell signaling pathways, which induce this fibrotic environment. This two-pronged attack would have the advantage of decreasing PaC cell growth, while allowing effective immunotherapy to fully destroy the remaining tumor cells.
Project: Memory-like natural killer (NK) cells for cancer immunotherapy
Principal Investigator: Todd A. Fehniger, M.D., Ph.D., Washington University School of Medicine in St. Louis
Natural killer (NK) cells are immune cells that eliminate cancer cells. Recent advances have demonstrated that pre-activation with cytokine proteins results in the differentiation of cytokine-induced memory-like (CIML) NK cells, which are long-lived and exert enhanced anti-tumor responses. We therefore initiated a first-inhuman clinical trial of CIML NK cell adoptive immunotherapy for patients with relapsed leukemia. Despite this rapid translational progress, our fundamental understanding of how memory-like NK cells differentiate and integrate with other NK cell-properties that influence responses to cancer are unknown. This study will address these significant and timely questions in the field by better defining how human memory-like NK cell function integrates with ‘licensing' rules that orchestrate an NK cell's decision to respond to a tumor cell. We will also seek to understand how changes in molecules or genes inside an NK cell may result in the enhanced anti-cancer function of memory-like NK cells. These results will provide a better understanding of how to select CIML NK cell donors, and new ways to further augment NK cell anti-tumor immunity. Finally, we will establish an important leukemia model system using mice, providing a critical tool to explore how to best combine CIML NK cells with other treatments, including a growth factor IL-15, to further increase or prolong CIML NK cell antitumor responses. This model could also be used to test other immunotherapy combinations in the future by blocking brake signals for NK cells or enhancing their ability to “see” or target different tumor types.
Project: Role of Subclones and Mutations in the Progression of MDS to Leukemia
Principal Investigator: Matthew J. Walter, M.D., Washington University School of Medicine in St. Louis
Myelodysplastic syndrome (MDS) is one of the most common blood cancers in people older than 65, affecting at least 30,000 people every year. Approximately 1 out of 3 MDS patients will progress to a rapidly fatal leukemia after being diagnosed with MDS. We know that mutations in the DNA of blood cells cause MDS and that additional mutations lead to leukemia. MDS cells that develop into leukemia contain unique mutations in their DNA that can serve as a fingerprint to identify these cells, which are often present months to years before the symptoms of leukemia develop. We can detect these rare cells prior to leukemia development using an ultra-sensitive sequencing assay we developed. Our goal is to use this ultra-sensitive sequencing assay to screen bone marrow cells from patients with MDS at regular time intervals to identify the growth of leukemia cells as early as possible so that treatments could be started prior to development of clinical symptoms. Ultimately, a better understanding of how these mutations affect blood cell development may allow us treat these rare leukemia cells and avoid clinical progression of MDS to leukemia.
Project: Mechanisms of Gastrointestinal Adenocarcinoma Tumorigenesis
Principal Investigator: Jason Mills, M.D., Ph.D., Washington University School of Medicine in St. Louis
Cancers of the colon, rectum, and stomach are among the most common and deadliest in the United States and throughout the world. One potential angle that could be pursued to limit their devastating impact would be to learn how to stop them essentially before they start. That might be possible, because they occur in the setting of long-standing pre-cancerous changes. Those pre-cancerous changes (metaplasias in the stomach and polyps in the intestines) could be prevented or potentially even reversed if we understood how they begin. This grant proposal will examine genes and cell-cell interactions that result in the initiation, maintenance, and progression of pre-cancerous lesions in the stomach and intestines. We will use mouse to model the changes, as well as tissue cultures of “organoids”, microscopic versions of stomach and intestine that we can grow from real patients in the Petri dish. Because the organoids are directly derived from real patients with their specific genetic makeup, we can study them as proxies to identify which genes are required for growth of precancerous lesions and, eventually, determine how an individual patient's genetic makeup interacts with potential therapeutic agents. We will identify these therapeutic drugs by screening organoid cultures with “libraries” of drugs.
Project: DNA Replication, Nuclear Architecture and Genome Stability
Principal Investigator: Dale Dorsett, Ph.D., St. Louis University School of Medicine
Cancer chemotherapy is designed to preferentially kill tumor cells based on their reduced ability compared to normal cells to accurately transfer their genetic information to their daughter cells when they divide. Cancer cells have a reduced ability to repair damage to their DNA caused by the chemotherapy drugs. The dreadful side-effects of chemotherapy occur because the drugs are not selective enough and also poison many normal cells. This limits the amount of drug that can be used, and the length of time that cancers can be treated, reducing the efficiency of chemotherapy. Thus many times not all tumor cells are killed, leading to cancer recurrence. Our goal is to increase the efficiency and selectivity of chemotherapy by understanding how cells normally ensure accurate transfer of genetic information, and how these mechanisms are altered in cancer cells, and in response to chemotherapy. Our work will focus on newly-discovered interactions between the Brca2 (familial breast cancer gene) protein that is needed to repair damaged DNA, and the Pds5 protein that is needed for cells to repair DNA and separate their chromosomes equally into the daughter cells when they divide. These proteins also interact with the Lamin A protein that maintains the structure of the cell nucleus, possibly to ensure that the functions of the Pds5 and Brca2 proteins occur in the appropriate regions of the nucleus. By discovering how these proteins work together, we will hopefully gain insights into how to increase the effectiveness of chemotherapeutic drugs.