10 Ohio State Cancer Research Projects Underway With Pelotonia Funding

July 13, 2016
3-D tumor microenvironment

COLUMBUS, Ohio – Ten more compelling cancer research studies have received funding from Pelotonia, the annual cycling movement that has raised more than $106 million for cancer research efforts at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James).

The 2016 Pelotonia Ideas Grants Program projects range from using liquid biopsy to characterize genomic-driven drug resistance and evaluating the relationship between the pregnancy-lactation cycle in the development of triple-negative breast cancer among African American women to a herpes-based vaccine designed to unleash the immune system to attack a rare but aggressive form of brain cancer.

In the past six years, 89 OSUCCC – James research teams have received Pelotonia Idea Grants, which provide funding support for two years. Awardees are selected through a peer-review process conducted by both internal and external scientists not competing for grants in the current funding year. A total of $948,348 will be awarded for this latest round of Pelotonia Idea Grants, with $8.82 million in funding awarded since the program’s inception. This represents the work of more than 175 investigators across 12 colleges plus Nationwide Children’s Hospital.

“In order make breakthrough progress in cancer research and cancer care, we must continue to find new ways to fund the bold new ideas put forth by top scientific minds. That’s what Pelotonia funds allow us to do – test the most promising ideas now – not five years from now – with the goal of creating a cancer-free world,” says Michael Caligiuri, MD, director of the OSUCCC and chief executive officer (CEO) of the James Cancer Hospital and Solove Research Institute.

Pelotonia 2016 takes place Aug. 5 - 7, 2016. For more information or to register, visit pelotonia.org.

“Thanks to the generous support of the Pelotonia community, we have the unique opportunity to provide seed money to teams of faculty researchers who are applying for external grants,” adds Doug Ulman, president and CEO of Pelotonia. “Because this area of research does not receive much funding, it is an honor for us to invest in brilliant ideas that lead to scientific discoveries that advance cancer research and ultimately save lives.”

Summaries of spring/summer Pelotonia Idea grant projects follow here.

Image-Guided, Catheter-Delivered Radiotherapy to Treat Low-Risk Prostate Cancer

Men diagnosed with very low-risk, localized prostate cancer have multiple choices for treatment, ranging from active surveillance – which involves frequent monitoring for disease via blood tests and clinical evaluations – to surgery to remove the entire prostate gland or targeted radiation treatments. Removing the whole gland carries a high risk of impotence, incontinence and gland function. About 80 percent of men diagnosed with prostate cancer are diagnosed with gland-localized, early stage disease that could theoretically be treated with cancer-targeted drugs if the exposure of normal tissues to these potent 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 one thousandth of the expected intravenous dose. Researchers will assess therapeutic outcomes as well as sexual and urinary side effects.

Mechanisms Behind Pregnancy-Lactation Cycle and Triple-Negative Breast Cancer

Previous studies suggest that giving birth and breastfeeding lowers 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 why childbirth and breastfeeding affect breast cancer risk remain unclear but research suggests that it is related to pro-inflammatory 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. Knowledge gained in this study is expected to enhance knowledge of the biological mechanisms underlying the connection between breastfeeding and breast cancer risk, particularly difficult-to-treat triple-negative breast cancers.

New Drug for Acute Myeloid Leukemia

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 responsible for producing blood cells. The complexity of gene abnormalities involved in disease’s development  – as well as the tumor microenvironment  – make identification of potential therapeutic targets particularly challenging. This preclinical study will test a new NAMPT inhibitor agent for the treatment of AML. The treatment agent is based on translational research discoveries made at The OSUCCC – James and is expected to provide important insights into the effects of this class of inhibitors on AML.

Early Biomarkers of Treatment Effectiveness, Toxicity in Sarcoma

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 to 40 percent of patients respond to the therapy. The combination frequently has life-threatening 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 be predictive of treatment response and toxicity.

  • Investigators: James Chen, MD, College of Medicine, David Liebner, MD, College of Medicine Ewy Mathe, PhD, College of Medicine

Using Herpes Virus to Train Immune System to Destroy Cancer Cells 

Despite two decades of research, few treatment advances have been made in the treatment of glioblastoma (GBM), a rare but deadly for of primary brain tumor with a median overall survival of less than 15 months. Oncolytic 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 designed to overcome the normal immune system checkpoints and 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 mechanisms involved in innate immunity and oncolytic virus interaction to help inform new virotherapies for GBM.

  • Investigator: Jianhua Yu, PhD, College of Medicine

3-D View of Micro-Environment To Study Development of Advanced Cancer  

The tumor micro-environment, which is composed of noncancerous cells and tissue within a solid tumor, is known to be an important regulator of tumor behavior and progression. How the conditions of the tumor become abnormal to create a hostile micro-environment that activates cancer cells, however, is still 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 micro-environment. Knowledge gained from this study is expected to advance the understanding of the physiological processes in the tumor micro-environment and to help develop therapeutic strategies for restraining the tumor promoting properties of the micro-environment.

Achilles’ Heel for Cancer Stem Cells

All cells in the body start as stem cells, which then differentiate into other cells that serve specific functions in the body. Some semblance of this cellular hierarchy exists in malignant tumors like glioblastoma (GBM) which are believed to have a subpopulation of cancer stem cells -- cells that harbor all the malignant characteristics of the disease and result in the disease being extremely resistant to radiotherapy and chemotherapy as well as invasive beyond the area of surgical resection. 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 and, therefore, improve patient outcomes.

‘Liquid Biopsy’ to Unlock New Cancer Treatment Options

Up to 40 percent of patients have a clinically actionable genomic alteration, however, only 10 percent of patients go on to receive treatment due to limited availability of therapies or clinical trials targeting their specific 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. The goal is to establish a foundation for implementing liquid biopsy in the clinic to help characterize drug resistance in patients and enable oncologists to better match patients with drug therapies more likely to achieve cancer control or reduction.

Lung Toxicity from Electronic Cigarettes and Tobacco Products

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 as well as how this compares to never-smokers of any product. Researchers hypothesize that e-cig constituents will induce lung inflammation and alter genomic and metabolomics 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

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 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 new insight on the role of the specific inflammation-regulator (NF-kB) in pancreatic cancer and identify new targets for the treatment of pancreatic cancer.

  • Investigator: Denis Guttridge, PhD, College of Medicine, Michael Ostrowski, PhD, College of Medicine


About the OSUCCC – James

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 49 National Cancer Institute-designated Comprehensive Cancer Centers and one of only four centers funded by the NCI to conduct both phase I and phase II clinical trials on novel anticancer drugs. As the cancer program’s 306-bed adult patient-care component, The James is one of the top cancer hospitals in the nation as ranked by U.S. News & World Report and has achieved Magnet designation, the highest honor an organization can receive for quality patient care and professional nursing practice. At 21 floors with more than 1.1 million square feet, The James is a transformational facility that fosters collaboration and integration of cancer research and clinical cancer care.

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