NEW PELOTONIA ‘IDEA GRANTS’ IN CANCER RESEARCH AWARDED AT OHIO STATE
COLUMBUS, Ohio – The Ohio State University’s Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC-James)
announced today 13 new research grants awarded through the 2012 Pelotonia Intramural Research Program. These multiyear grants, termed “Idea Grants” because they present innovative approaches to understanding and curing cancer, are funded primarily by dollars raised through Pelotonia, a grassroots bicycle tour established in 2009 to raise money for cancer research at Ohio State. A total of 29 Idea Grants have been awarded the last three years since the inception of Pelotonia at an investment approaching $5 million dollars to date.
“Conquering cancer requires discoveries in the biology and genetics of cancer, in targeted therapies that focus on specific cancer cells, and in more effective ways to preempt and prevent cancer from happening in the first place,” said Dr. Michael Caligiuri, director of the OSUCCC and CEO of the James Cancer Hospital and Solove Research Institute
. “But cancer research is very expensive. The dollars raised through Pelotonia provide Ohio State with resources to recruit the best and the brightest minds, to have the tools, technology and instrumentation needed to conduct the research, and to fund new, bold ideas – ideas that without the support of Pelotonia would likely remain unexplored. These 13 new grants offer a continuing promise and hope for a cancer-free world.”
The grants address a broad range of issues and challenges from finding ways to maximize omega-3 fatty acids in the fight against breast cancer to improving targeted treatments for elderly patients with acute myeloid leukemia; from searching for new genetic markers for certain cancers to exploring how black raspberries can help prevent oral cancer.
“These new ideas can now become reality which shows the difference that each person makes when he or she rides or donates to Pelotonia,” Caligiuri said. “With federal funding for cancer research diminishing, we have to find alternative ways to keep cancer research progressing and to keep new generations of cancer scientists coming into the field. Pelotonia helps us bridge that gap.”
A list with the description of each award is attached.
Chemotherapy-Induced Cognitive Deficits: Dr. Lustberg and Dr. DeVries
More than 30 percent of breast-cancer patients who receive chemotherapy report problems with memory, concentration, attention and understanding during and after treatment. Even though this is a common problem and significantly affects quality of life, the cause of these cognitive deficits is poorly understood and there is no effective treatment for them. These researchers hypothesize that chemotherapy leads to inflammation of certain brain cells, altering the cells’ structure and function, which causes cognitive problems. The study will carry out four experiments that will help establish the biological mechanism through which chemotherapy alters cognition. This research is the first to test the idea that inflammation of neurons contributes to the development of cognitive impairment in chemotherapy patients.
The role of microvesicles in multiple myeloma: elucidating mechanisms of disease propagation and immune suppression and novel targets for intervention: Dr. Benson and Dr. Pichiorri
Multiple myeloma (MM) is a cancer of white blood cells called plasma cells. MM cells require growth factors and other substances produced by normal bone-marrow cells for their growth and survival. The interactions between MM and cells could be important therapeutic targets, but little is known about how they occur. These researchers believe that microvesicles – tiny particles sometimes given off by cells – might serve as important messengers between MM and normal cells. This study will analyze the contents of microvesicles from MM patients and how the vesicles might function in MM-cell communication. It will also explore whether the vesicles play a role in suppressing the body’s immune response to MM. The findings will improve the understanding of the role of microvesicles in MM and could lead to new treatments for the malignancy.
Role of RAC1 GTPase in astrocytoma initiation: Dr. Kwon and Dr. Yoon
Malignant astrocytomas are highly fatal brain or spinal tumors that have no effective treatment. To find better therapies, it is essential to understand how astrocytomas begin. Evidence suggests the regulation of oxygen radicals – unstable oxygen molecules that react with other molecules in the cell – is critical for tumor initiation, but how oxygen radicals levels are regulated is unclear. Using an astrocytoma mouse model, this study will focus on a gene called Rac1 and a gene called Prdx4, both of which are involved in regulating oxygen radicals in cells. It will explore whether the loss or suppression of these genes, and the resulting loss of oxygen radical formation, is involved in the initiation of astrocytomas. If so, there are a number of small molecules that are known to induce oxygen radical production in cells, and these molecules might be useful for astrocytoma treatment.
Combined EGFR and BRAF blockade in patients with advanced malignancies and BRAF mutant tumors: Dr. Villalona
Metastatic melanoma often has mutations that over-activate a cancer-causing gene called BRAF. Drugs called BRAF inhibitors target the overactive gene and can help melanoma patients. Similar BRAF mutations are found in other cancers, including thyroid and colorectal cancers and non-small cell lung cancer. BRAF inhibitors might help these patients, too, except that these cancers often have high levels of a molecule called EGFR. Tumors with high EGFR are often resistant to BRAF inhibitors. This study tests the use of a BRAF inhibitor plus an EGFR inhibitor in patients with colorectal cancer, non-small cell lung cancer and other solid tumors with BRAF mutations. The study will demonstrate the feasibility of combining the two inhibitors in these patients and establish recommended doses for the agents. It will also evaluate EGFR activation in BRAF-mutant lung and colorectal tumors before and after the BRAF inhibitor is given, both in the presence and absence of the EGFR inhibitor.
Eicosanoids as biomarkers of dietary w-3 fatty acid exposure and response: Dr. Yee
Evidence indicates that low levels of inflammation, which occur with metabolic diseases such as obesity and diabetes, can raise the risk for breast cancer. There is also good evidence that omega-3 fatty acids, found in fish oil and fatty fish, can reduce such inflammation. This project analyses biospecimens collected during two omega-3 fatty acid intervention studies in women at high risk for breast cancer. It will determine changes in levels of eicosanoids, molecules derived from the metabolism of omega-3 fatty acids. The findings will provide essential data regarding omega-3 fatty acid markers of exposure and response to support the initiation of a definitive breast-cancer prevention trial of omega-3 fatty acids in high-risk women.
The impact of stromal PTEN status on pathological complete response rates to neoadjuvant dual HER2-targeted therapy: Dr. Shapiro and Dr. Olson
Solid tumors contain both cancer cells and noncancer cells, called stromal cells. Evidence shows that genetic changes in stromal cells can influence the behavior of the cancer cells and vice versa. For example, mammary tumors in mice grow faster and more aggressively when certain stromal cells in them have low levels of a protein called PTEN. About 50 percent of human breast-cancer patients have low PTEN levels. This clinical trial will determine whether women with HER2-postive breast cancers that have higher versus lower PTEN levels in stromal cells have higher or lower remission rates after treatment with a combination of two drugs, trastuzumab and lapatinib, compared to breast tumors having normal stromal PTEN levels. If this proves correct, it will provide evidence that a tumor’s cancer cells and stromal cells should be considered together as a “treatment unit.” More importantly, it will be the first study to demonstrate that PTEN may be a predictive biomarker for women who are more (or less) likely to respond to dual therapy.
Decitabine followed by NK-cell immunotherapy for treatment of elderly patients with AML: Dr. Vasu and Dr. Yu
In patients older than age 60, acute myeloid leukemia (AML) is a devastating disease, with 5-year survival rates below 10 percent. Allogeneic bone marrow transplantation extends life in many AML patients, but many elderly patients are ineligible for the therapy. This study tests whether older AML patients treated with the DNA hypomethylating agent called decitabine plus infusions of cancer-fighting immune cells called NK-cells might improve treatment for older AML patients.
Testing the Feasibility of a Contingency Management Intervention to Encourage Medicaid-Enrolled Smokers to Quit: Dr. Ferketich and Dr. Seiber
Contingency management (CM) interventions use an incentive, usually a reward, to encourage people to change a behavior. This pilot study tests the use of a CM intervention to promote tobacco abstinence among Medicaid-enrolled smokers in Appalachia Ohio. Ten study participants form a control, or comparison, group; they receive counseling that encourages them to quit nicotine use and nicotine replacement therapy. Ten more participants form the intervention group; they receive counseling, nicotine replacement therapy and CM. The intervention participants create videos of themselves breathing into a carbon monoxide (CO) monitor and then show the result to the camera. For each CO reading that demonstrates tobacco abstinence, intervention participants receive escalating payments. All participants will receive $25 for completing a questionnaire at the study’s start and one after three months, the study’s end. The researchers will use data from this study to apply for National Institutes of Health funding to conduct study a tobacco-dependence treatment intervention for Medicaid smokers that will include a CM component.
Pancreas Specific microRNA Knockout for Tumorigenesis Study: Dr. Schmittgen and Dr. Coppola
Pancreatic cancer is one of the most lethal forms of cancer. Recent evidence suggests that noncoding microRNAs (miRNAs) might play an important role in initiating this disease. This study tests the idea that the loss of two miRNAs, miR-216 and miR-217, contributes to the development of pancreatic cancer (which would mean that they function as tumor suppressors in pancreatic cancer). To test this hypothesis, the researchers will develop a strain of mice that lack these two miRNAs. They will cross these mice with a second strain of mice that have a gene mutation that causes these animals to develop the most common form of pancreatic cancer. This study will evaluate the offspring of the cross to learn if the loss of miR-216 and miR-217 further increases the development of pancreatic cancer. The findings will provide new and fundamental information about the role of these two miRNAs in the development and progression of pancreatic cancer. The findings might also indicate that miRNA replacement could be a new form of pancreatic cancer treatment.
Pan-cancer MRI agents that self-assemble in malignant tumors: Dr. Tweedle and Dr. Goldberger
Getting anticancer drugs and imaging agents selectively into tumors and not healthy tissue remains a challenge. Many drugs target receptors on the cancer-cell surface, but cancer cells mutate rapidly, altering receptor structure and allowing tumors to escape receptor-targeted drugs. These investigators have developed a vehicle for delivering imaging agents and anticancer drugs to tumors that does not rely on specific receptors. The molecule, called a peptide amphiphile (PA), is composed of amino acids and lipids. The PA is a sphere at normal serum pH (7.3-7.4), but at the lower pH of a tumor (6.6-7.0), it transforms into larger nanofibers. This transformation would both release anticancer drugs packaged within the spheres and trap imaging agents built into the PA. In this study, the researchers will refine the PA structure so that the transition occurs pH 6.6-7.0 inside a living animal and demonstrate for the first time that the vehicle will be selectively retained in tumors in an animal model using the proposed mechanism.
Phytochemical release rate from black raspberry confections alters gene expression and chemical profiles relevant to inhibition of oral carcinogenesis: Dr. Vodovotz, PI; Dr. Clinton, Dr. Schwartz, Dr. Weghorst, and Dr. Pearl
Oral cancer is a devastating, global disease. These investigators are developing a strategy for preventing oral cancer in people at high risk for the disease by using formulations of black raspberries, which have been shown to have anticancer activity. The researchers have developed a series of confections that release black raspberry phytochemicals in the mouth at varying rates. This study will support a clinical trial involving 60 healthy adults who will use the confections over two weeks at two doses of black raspberry phytochemicals and released at three different rates. Data such as phytochemical profiles and gene expression profiles in biological samples will be collected to determine optimal dose and release rates. This information will be used for a future phase II study in high risk populations evaluating the confections for oral cancer prevention or therapy.
Impact of Androgen Deprivation Therapy on Cardiac Function in Prostate Cancer Patients: Dr. Clinton, PI; Dr. Raman, Dr. Simonetti, and Dr. Focht
Androgen deprivation therapy (ADT) is the most significant treatment ever developed for men with prostate cancer. It is often a component of therapy intended to cure men with high-risk localized prostate cancer or to limit the progression of metastatic disease. But ADT is also linked to loss of skeletal muscle mass, lower bone mineral density, greater risk of metabolic syndrome and of a fatigue syndrome. These effects cause declines in performance status and in quality of life. These researchers are currently doing NIH-funded research to quantify these declines in performance and quality of life in men on ADT, and to identify a diet and exercise program that will prevent the declines. This cardiac function study complements that work. It will quantify changes in cardiac performance in men on ADT using the novel non-magnetic treadmill stress test and cardiac MRI system developed at Ohio State. The findings will help determine dietary and exercise interventions that will prevent or reduce the deleterious consequences of ADT on cardiovascular health, physical performance and quality of life.
Developing a combination therapy using ATM inhibitor and γδ T cells for breast cancer: Dr. Das and Dr. Shapiro
Laboratory studies by these researchers have shown that a subtype of immune cell called γδ T cells limit the growth of multiple subtypes of breast-cancer cells by causing many of the cells to die by triggering a natural form of cell death called apoptosis. The researchers have also shown that γδ T cells can strongly inhibit tumor growth in at least one type of breast-cancer in an animal model. The researchers have also learned the mechanism by which γδ T cells trigger the death of breast-cancer cells. In this study, they want to apply this knowledge and test the use of drugs ATM inhibitors to learn if those agents, combined with γδ T cells, can more efficiently control tumor growth in an animal model than current treatments.
The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
strives to create a cancer-free world by integrating scientific research with excellence in education and patient-centered care, a strategy that leads to better methods of prevention, detection and treatment. Ohio State is one of only 41 National Cancer Institute
(NCI)-designated Comprehensive Cancer Centers and one of only seven centers funded by the NCI to conduct both phase I and phase II clinical trials. The NCI recently rated Ohio State’s cancer program as “exceptional,” the highest rating given by NCI survey teams. As the cancer program’s 210-bed adult patient-care component, The James is a “Top Hospital” as named by the Leapfrog Group and one of the top cancer hospitals in the nation as ranked by U.S. News & World Report.
Pelotonia consists of a three-day experience that includes cycling, entertainment and volunteerism. Pelotonia riders agree to a personal grassroots fundraising commitment that involves requesting donations from friends and family. Over the past three years, thousands of Pelotonia riders have raised over $25 million for cancer research at The Ohio State University Comprehensive Cancer Center. Due to the generosity of Pelotonia’s funding partners, the organization is able to direct 100 percent of all donations to life saving cancer research.
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Contact: Eileen Scahill, Wexner Medical Center Public Affairs and Media Relations, 614-293-3737, or Eileen.Scahill@osumc.edu