Teaming Up Against Cancer
Pelotonia Funds Support 10 More Cancer Research Projects
Another 10 compelling cancer research studies being conducted by teams of Ohio State faculty scientists received grant funding in summer 2016 from Pelotonia. All 10 were funded by the OSUCCC – James Intramural Research Program (IRP), which is supported by Pelotonia.
IRP funding comes in several forms, including:
- Idea Grants, which support high-risk, high-payoff research for which government grants are difficult to obtain;
- Community Partnership Awards, which support investigators who team with a community entity on a cancer-focused study;
- Clinical Trial Awards (protocol-specific research support), which support studies that seek ways to prevent, diagnose and treat cancer and provide participating patients with some of the most advanced treatments available anywhere;
- Bridge Funding Awards, which help researchers with competitive renewal applications for National Cancer Institute (NCI) grants that were not funded on their first submission, or for grants whose initial funding has expired.
This Pelotonia-supported funding is vitally important at a time when government funding is hard to obtain for the early pursuit of promising studies.
“The creative projects funded by this program involve ideas from scientists who are ‘thinking outside the box’ and need support for gathering early data that will enable them to apply later for larger external grants from entities such as the National Cancer Institute,” says OSUCCC Director and James CEO Michael A. Caligiuri, MD. “Our scientists could not pursue these innovative projects without funding raised by the thousands of riders in Pelotonia.”
In the past six years, 89 OSUCCC – James research teams have received Pelotonia-funded IRP grants awarded through a peer-review process conducted by both internal and external scientists who are not competing for grants in the current funding year. This latest round of grants totals $948,348. Here are summaries of each project:
Image-Guided, Catheter-Delivered Radiotherapy to Treat Low-Risk Prostate Cancer
(Investigator: Michael Tweedle, PhD, College of Medicine)
Men diagnosed with low-risk, localized prostate cancer have multiple choices for treatment, ranging from surveillance—which involves frequent monitoring for disease via blood tests and clinical evaluations—to surgery to remove the entire prostate gland, to targeted radiation treatments. Removing the prostate carries a high risk of impotence, incontinence and gland function. About 80 percent of men diagnosed with prostate cancer have gland-localized, early-stage disease that could theoretically be treated with cancer-targeted drugs if the exposure of normal tissues to these drugs could be eliminated. This preclinical study will evaluate a gland-sparing alternative to treat prostate cancer. Researchers hypothesize that an image-guided, super-selective micro catheterization of the prostate arteries could be used in combination with a novel peptide receptor radionuclide therapy to treat prostate cancer confined to the gland using 1,000th of the expected intravenous dose. They will assess therapeutic outcomes along with sexual and urinary side effects.
Mechanisms Behind Pregnancy-Lactation Cycle and Triple-Negative Breast Cancer
(Investigator: Bhuvaneswari Ramaswamy, MD, College of Medicine)
Previous studies suggest that giving birth and breastfeeding lower a woman’s overall risk of developing breast cancer, with the most recent data pointing to breastfeeding being protective specifically against triple-negative breast cancers. African-American/ black women have a disproportionately high rate of developing aggressive triple-negative breast cancer while also having higher birth rates and lower rates of breastfeeding. Research has also shown that women native to Africa have higher rates of breastfeeding and lower rates of breast cancer. The reasons that childbirth and breastfeeding affect breast cancer risk remain unclear, but research suggests it is related to proinflammatory processes coordinated by STAT3 activation. This basic science study will test the hypothesis that an overarching biologic mechanism in African women leads to elevated STAT3 activation, triggering a proliferative/ inflammatory environment in the breast tissue that results in a higher risk for breast cancer.
New Drug for Acute Myeloid Leukemia
(Investigators: Rosa Lapalombella, PhD, and John C. Byrd, MD, both of the College of Medicine)
Acute myeloid leukemia (AML) is a complex form of blood cancer characterized by the rapid accumulation of neoplastic myeloid cells in the bone marrow, a soft fatty substance inside bones that is responsible for producing blood cells. The complexity of gene abnormalities involved in disease development—as well as the tumor microenvironment—makes it a challenge to identify potential therapeutic targets. This preclinical study will test a new inhibitor agent for the treatment of AML. The treatment agent is based on translational research discoveries made at the OSUCCC – James and may provide important insights into the effects of this class of inhibitors on AML.
Early Biomarkers of Treatment Effectiveness, Toxicity in Sarcoma
(Investigators: James Chen, MD, David Liebner, MD, and Ewy Mathe, PhD, all from the College of Medicine)
Soft tissue sarcomas affect about 12,000 adults annually in the United States and are associated with very high mortality rates, with most patients who have metastatic disease surviving less than 15 months. High-dose adriamycin in combination with ifosamide (HD-AIM) remains the gold standard chemotherapy treatment for sarcoma, but just 30-40 percent of patients respond to the therapy. The combination frequently has lifethreatening side effects. Identifying patients most likely to benefit from HD-AIM will improve effectiveness of this therapy and reduce deaths due to drug toxicity. In this clinical study, researchers will use metabolomics—a comprehensive quantification of small molecules from the tumor and drugs found in bodily fluids—to identify prognostic biomarkers in sarcoma. Based in the medical oncology sarcoma program, this clinical study seeks to identify early changes in urine and blood metabolites of soft tissue sarcoma patients undergoing HD-AIM therapy to determine whether these biologic measures can predict treatment response and toxicity.
Using Herpes Virus to Train Immune System to Destory Cancer Cells
(Investigator: Jianhua Yu, PhD, College of Medicine)
Despite two decades of research, few treatment advances have been made for glioblastoma (GBM), a rare but deadly form of primary brain tumor with a median overall survival of less than 15 months. Oncolytic (cancer-killing) viral therapy is an emerging concept for new anticancer treatments that uses naturally occurring, replicating viruses engineered to infect and destroy cancer-specific cells. OSUCCC – James researchers have engineered an oncolytic virus based on the herpes simplex virus 1 designed to emit a “don’t eat me” signal to the immune system so the virus can infect/ destroy the targeted cancer cells. This basic science study will explore the molecular mechanisms behind natural immune system responses to the oncolytic virus to gather critical knowledge about the biological processes involved in innate immunity and oncolytic virus interaction, possibly leading to new virotherapies for GBM.
3-D View of Microenvironment to Study Developmeny of Advanced Cancer
(Investigator: Jonathan Song, PhD, College of Engineering)
The tumor microenvironment, which is composed of noncancerous cells and tissue within a solid tumor, is an important regulator of tumor behavior and progression. How the conditions of the tumor become abnormal to create a hostile microenvironment that activates cancer cells, however, is poorly understood. This basic science study will combine principles from microtechnology and tissue engineering to develop a disease model of advanced cancers to enable 3-D imaging and analysis of molecular pathway changes conferred by the tumor microenvironment. Knowledge gained from this study may boost understanding of the physiological processes in the tumor microenvironment and help develop therapeutic strategies for restraining its tumor-promoting properties.
Achilles’ Heel for Cancer Stem Cells
(Investigator: Monica Venere, PhD, College of Medicine)
All cells in the body start as stem cells that differentiate into other cells that serve specific functions. Some semblance of this cellular hierarchy exists in malignant tumors like glioblastoma (GBM), which are believed to have a subpopulation of cancer stem cells, or cells that harbor the malignant characteristics of the disease and cause it to resist radiotherapy and chemotherapy. This basic science study will explore the role of cancer stem cells in the development of radiotherapy resistance with the aim of finding an “Achilles’ heel” for cancer stem cells. Researchers hypothesize that the protein K1F11 plays a direct role in the radiotherapy response, and that therapy targeting K1F11 given in conjunction with radiotherapy would be more effective for overcoming treatment resistance, therefore improving patient outcomes.
‘Liquid Biopsy' to Unlock New Cancer Treatment Options
(Investigator: Sameek Roychowdhury, MD, PhD, College of Medicine)
Up to 40 percent of patients have a clinically actionable genomic alteration, but only 10 percent of patients go on to receive treatment due to limited availability of therapies or clinical trials targeting their gene mutations. Several barriers to cancer genomic testing in patients exist, including easy access to tumor specimens that may represent the patient’s current metastatic disease, and limitations to DNA sequencing/lack of clinical-grade RNA sequencing. In this clinical study, researchers will use liquid biopsy to test for DNA and RNA through routine blood and urine samples. They hope to establish a foundation for implementing liquid biopsy in the clinic to help characterize drug resistance in patients. This would enable oncologists to better match patients with drug therapies that are more likely to achieve cancer control or reduction.
Lung Toxicity From Electronic Cigarettes and Tobacco Products
(Investigator: Peter Shields, MD, College of Medicine)
Electronic cigarettes (e-cigs), which deliver aerosolized nicotine and flavorings through a battery-operated device, have gained rapid popularity, particularly among never-smokers and youth users. Although they are touted as smoking-cessation tools, there is no scientific data to support this claim and very little data describing the health effects of using e-cigs as compared with the use of other tobacco products. This grant expands the scope of two ongoing research studies to evaluate the differences in lung toxicity between smokers and e-cig users, and to see how this compares to never-smokers of any product. Researchers hypothesize that e-cig constituents will induce lung inflammation and alter genomic and metabolomic gene expression pathways. The pilot study will also establish the feasibility of using bronchoscopy as a way to measure lung toxicity and identify candidate genes for biomarker development.
Decoding Genetic Mutation's Role in Pancreatic Cancer
(Investigators: Denis Guttridge, PhD, and Michael Ostrowski, PhD, both of the College of Medicine)
Although there have been advances in abdominal imaging, surgical techniques and chemotherapy regimens for pancreatic cancer, the death rates for the disease have not decreased significantly since the 1940s. Of the 53,000 people diagnosed with the disease annually, just 7 percent are expected to live five years after diagnosis. This basic science study will help researchers understand the relationship between Kras—one of the most common gene mutations found in human pancreatic cancer—and disruptions in the cellular checkpoints for inflammation that would normally serve to stop cancerous tumors from developing and growing. Data gathered in this study could provide insight on the role of an inflammation-regulator called NF-kB in pancreatic cancer and identify new targets for treating this disease.