11 Additional Ohio State Cancer Research Projects Underway With Pelotonia Funding

March 23, 2017
Genetic testing at The OSUCCC James

COLUMBUS, Ohio – Eleven breakthrough cancer research ideas have received funding from Pelotonia, the annual cycling movement that has raised more than $130 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 2017 Pelotonia Idea Grants Program projects range from understanding the protective effects of female hormones against melanoma and helping breast cancer patients navigate treatment choices to identifying new genes linked to aggressive prostate cancer and understanding the role of specific genetic mutations in an aggressive form of leukemia.

In the past seven years, more than 100 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 $1.08 million will be awarded for this latest round of Pelotonia Idea Grants, with $10 million in funding awarded since the program’s inception. This represents the work of investigators across eight colleges plus Nationwide Children’s Hospital as well as Cincinnati Children’s Hospital and The Ohio State University Wexner Medical Center.

“Pelotonia has provided a tremendous opportunity for The Ohio State University Comprehensive Cancer Center (OSUCCC) to accelerate our research efforts. With the dollars generated through Pelotonia, we have funded more than 100 innovative new idea grants, three statewide cancer research initiatives (colon, lung and endometrial cancer), launched early-stage drug development efforts through our embedded biotech enterprise (the Drug Development Institute), brought digital pathology to Columbus and provided more than 400 scholarships to students with an interest in cancer,” says Michael Caligiuri, MD, director of the OSUCCC and CEO of the James Cancer Hospital and Solove Research Institute. “Thanks to our community’s effort, we are able to continue funding some of the boldest new ideas put forth by top scientific minds, including those from the next generation of oncology researchers.”

Pelotonia 17 will take place Aug. 4 - 6. For more information or to register, visit pelotonia.org.

“It is an honor for our community of riders and donors to be able to invest in brilliant ideas that advance cancer research and ultimately save lives for those affected by a disease that has touched so many of us personally,” adds Doug Ulman, president and CEO of Pelotonia. "We are excited to continue working with our growing Pelotonia movement toward our shared goal of ending cancer.”

Summaries of winter/spring Pelotonia Idea grant projects follow here:

Understanding Potential Protective Effect of Female Hormones in Melanoma

Research shows that men are more susceptible to melanoma than women and more frequently die of the disease. While sex-specific incidence and mortality rates are well established, molecular mechanisms to explain these observations are not fully understood. Melanoma often arises from moles that harbor cancer-promoting mutations (oncogenes) such as BRAF and NRAS. Although the majority of moles with these properties do not transform into cancer, some do and this progression to cancer is thought to be linked to a secondary genetic hit that occurs due to ultraviolet radiation (UV) exposure. Growing scientific data also suggests that the hormone estrogen has a protective effect against melanoma in women. In this study, researchers will assess the role of a certain form of the estrogen receptor in melanoma onset and progression to help identify estrogen-dependent gene targets that protect against melanoma.

Genomic Drivers of Race Disparity in Triple-Negative Breast Cancer

Among all the breast cancer subtypes, triple-negative breast cancer has a high rate of mortality due to a lack of clinically established biomarkers and effective targeted therapy. Population-based studies also point to clear evidence of racial disparities, including younger age, higher incidence rates and aggressiveness of triple-negative breast cancer at diagnosis and poor survival among black women compared with white women. A more robust understanding on the molecular mechanisms behind this phenomenon is needed to develop more effective treatments. This study will further investigate whether a specific gene (S100A7) – which has been shown to increase inflammation – also has a role in growth and metastasis of triple-negative breast cancer. The overall objective of the study is to understand specific molecular crosstalk between numerous genetic pathways and inflammatory markers, and how that interaction influences cancer development and spread.

Therapy to Restore Breathing, Swallowing in HPV+ Head and Neck Cancer Patients

Head and neck cancer is one of the fastest growing cancers in the world, largely due to the increasing incidence of HPV (human papillomavirus). Head and neck cancer patients with HPV+ tumors are often treated with organ-sparing therapies, including chemoradiation that results in a high level of cancer control. The treatment can produce debilitating side effects, however, including the inability to eat or swallow. Patients who have ineffective swallowing as well as airway impairment are susceptible to aspiration pneumonia and often become malnourished, leading to high death rates in this population. This project will evaluate the use of expiratory muscle strength training (EMST) in patients with HPV+ head and neck cancer treated with chemoradiation. The therapy currently is used in some degenerative muscular diseases to improve swallowing function. Researchers will measure the clinical impact of traditional swallow intervention studies versus traditional swallowing interventions plus EMST on swallowing and respiratory function.

Personalized Combination Drug Therapy for Melanoma

  • Investigator: Fuhai Li, PhD, College of Medicine (Biomedical Informatics)

Despite recent advances in targeted and immune-based therapies, the majority of melanoma patients eventually become unresponsive to treatment. New combination drug therapies to curb drug resistance could improve response rates of existing therapies. However, more efficient methods of predicting which current drugs can be repurposed for combination therapy and personalized medicine applications are needed. In this project, researchers will seek to validate a computational drug-repurposing approach called Medical Doctor Miner (MD-Miner) that was developed at the OSUCCC – James. The tool integrates personal genomics profiles of individual patients with multiple scales of drug data for thousands of FDA approved drugs and active compounds simultaneously to predict potentially effective drug combinations tailored to individual patient samples.

Decision Making and Communication Among Breast Cancer Patients Choosing Preventive Mastectomies

More and more women with breast cancer have been undergoing contralateral preventive mastectomies in the past 10 years. The National Comprehensive Cancer Network recommends this surgical procedure for patients with a BRCA gene mutation or strong family history to reduce risk of cancer, however, it is primarily performed in patients without a mutation or family history (sporadic breast cancer cases), who do not need the procedure for medical reasons. This study will evaluate treatment decisions in early-stage breast cancer patients to assess how communication with their providers affects their decision-making. It will also examine their knowledge, preferences, and expectations about future well-being. Information from this study is expected to help clinicians develop tools to aid patients in making an informed decision about their care.

Examining Skin Cancer as a Predictor of the Development of New Internal Primary Cancer

Ultraviolet light (UV)-induced keratinocyte carcinomas (non-melanoma skin cancers) are the most common form of cancer in humans, with more than 3.5 million new cases diagnosed in the United States annually. Worldwide epidemiological studies have reported a connection between a history of UV-induced non-melanoma skin cancers and an increased risk of developing a secondary, non-skin primary cancer. A subset of patients with squamous cell carcinoma (SCC) has a 25 percent higher risk of dying from that secondary cancer, though the reason remains unclear. In this study, researchers will study the link between SCC and colon cancer development in a preclinical model to determine the effects of the developing colon tumors on UVB-induced skin cancer development. Researchers will also seek to understand whether the presence of UV-induced skin cancer influences colon tumor development. The study is expected to provide important insights into the relationship between skin tumors and second primary cancers.

“Research Autopsy” to Understand Unique Molecular, Genetic Characteristics of Advanced Cancers

Scientists have discovered that not all cancer cells in a patient’s body are alike -- calling this phenomenon  “tumor heterogeneity.” Tumor heterogeneity can cause some cancer cells to become resistant to treatment and explain why some cancers recur after treatment. Using rapid research autopsy, the study team will obtain samples of cancer cells from different organs of patients who have died of their cancer. The team will study their genomes to determine how certain cancer cells acquire resistance and use this knowledge to advance the discovery of new cancer drugs. The study will also evaluate liquid biopsy – a method of measuring circulating tumor DNA through urine or plasma. This precious donation from patients will facilitate research to help accelerate new cancer drug development and help guide individualized therapy for patients by contributing to the oncology community’s understanding of the molecular and genetic variation that exists in cancer.

Cellular Membrane Trafficking as Targets for Multiple Myeloma 

Multiple myeloma is a form of blood cancer that affects the plasma cells, infection-fighting white blood cells that originate in the bone marrow. Even with aggressive treatment, multiple myeloma remains an incurable disease, and identifying new targets for therapy is critical. In this basic science study, researchers will seek to further identify and target specific components that are dispensable in normal cells but become essential during the aberrant clonal cell expansion that characterizes plasma cell neoplasia. The hope is to develop a novel and effective therapeutic approach for multiple myeloma.

Potential New Cancer-Promoting Gene in Prostate Cancer

The male hormone testosterone promotes the growth of prostate cancer through its binding to the androgen receptor in cancer cells. AR-V7 is a mutant variant of the androgen receptor that no longer requires testosterone binding to signal the growth and progression of prostate cancer. This specific mutation acts to accelerate prostate cancer growth and is a common and important step toward the lethal phase of human prostate cancer. However, therapeutic strategies targeting AR-V7 do not exist. This study will define the mechanisms underlying the cancer-promoting function of AR-V7 and will identify new therapeutic strategies for advanced prostate cancer.

Clinical Impact of Genetic Mutations in Leukemia

Core-binding factor acute myeloid leukemia (CBF-AML) is a form of cancer that affects blood-forming tissue (bone marrow) defined by the presence of specific genetic mutations. The resulting presence of a merged genetic mutation, or fusion gene, is not capable of causing leukemia independently. Researchers believe a “second hit” is necessary for leukemia to develop. Almost 40 percent of CBF-AML patients will experience a relapse of their disease, so a better understanding of the molecular events that lead to cancer formation is critical. In this study, researchers will test clinical and outcome associations of two genetic mutations (CCND1 and CCND2) known to play a role in the development of CBF-AML. This will help scientists better understand the role of CCND1/CCND2-mediated leukemia to help develop more therapeutic targets. 

Single-Molecule Studies of DNA Base Excision Repair

  • Investigator: Zucai Suo, PhD, College of Arts and Sciences (Chemistry and Biochemistry)

In this basic science study, researchers will seek to better understand the role of a specific DNA damage repair pathway -- DNA base excision repair (BER) -- in cancer development and progression. The team will conduct laboratory studies aimed at understanding the molecular mechanisms behind the cellular functions of BER and the cascade of events that lead to cancer development. Knowledge gleaned from this study could help scientists develop new targets for cancer treatment.

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 47 National Cancer Institute (NCI)-designated Comprehensive Cancer Centers and one of only a few centers funded by the NCI to conduct both phase I and phase II clinical trials on novel anticancer drugs sponsored by the NCI. As the cancer program’s 308-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 and 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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Amanda J. Harper
OSUCCC – James Media Relations

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