Asking questions that lead to brilliant ideas is at the root of scientific discovery. Quantum leaps in science are made by this type of innovative thinking, but funding for the early pursuit of such initiatives is hard to obtain.
In the past seven years, 108 OSUCCC – James teams have received Pelotonia Idea Grants. Since the program’s inception, $11.1 million in funding has been awarded. This represents the work of more than 175 investigators across 12 colleges plus Nationwide Children’s Hospital.
The awards are issued via a peer-review process conducted by scientists not competing for the grants. The grants cover an array of studies, from the genetics of triple-negative breast cancer to imaging of precancerous pancreatic lesions; from neurofibroma tumorigenesis and therapy to the molecular mechanisms of the body’s natural killer cells against multiple myeloma; from the role of the ATF3 gene in the development and treatment of chronic lymphocytic leukemia to genomic aberrations driving metastatic squamous cell carcinoma (a type of skin cancer).
Most Recently Funded Projects
Understanding Cancer Stem Cells in Ovarian Cancer
Investigator: Qi-En Wang, MD, PhD, College of Medicine (Radiology), OSUCCC – James Molecular Carcinogenesis and Chemoprevention Research Program
Only 45 percent of ovarian cancer patients reach the five-year survival mark, mainly due to high rates of advanced disease and disease recurrence. Researchers believe cancer stem cells are the root of many solid tumors, including ovarian. OSUCCC – James researchers recently discovered a protein (DDB2) that stops the growth of ovarian cancer stem cells. This study further investigates mechanisms by which DDB2 stops cancer stem cell survival. Results may lead to better strategies for preventing ovarian cancer spread and recurrence.
Evaluating New Targets for Glioblastoma Treatment
Glioblastoma (GBM) is the most common type of adult malignant brain tumor. Because most patients live only 12 to 15 months after diagnosis, new molecular targets are needed to improve patient survival. Guo and team recently revealed that a protein called SCAP is essential for activation of SREBP-1, a gene/protein involved in GBM growth. This study will advance knowledge of how cellular metabolism is “reprogrammed” in GBM— information that could help identify new molecular targets for the disease.
Improved Imaging for Bladder Cancer Diagnosis and Staging
Accurate staging of bladder cancer can be difficult with the imaging tools currently available, making it hard for urologists to recommend the best treatment for each patient’s disease characteristics. This study will develop pathological image analysis tools to accurately stage and stratify patients by disease risk. This will help urologists make treatment decisions that balance the best chance of long-term cancer control while avoiding over-treatment.
Stimulating the Immune System to Fight Cancer
Cancer activates cells that interfere with the immune system’s ability to kill cancer. Recent OSUCCC – James research showed that these cells—known as myeloid- derived suppressor cells—can be stopped with the drug ibrutinib. In preclinical studies, researchers also showed that ibrutinib was most effective in combination with a second drug that activates immune-boosting T-cells called immune checkpoint inhibitors. Initial results showed a complete elimination of breast cancer tumors in 50 percent of subjects treated with ibrutinib and immune checkpoint inhibitors. The team will conduct a pilot study to confirm these results in patients with metastatic solid tumors who will receive the immunotherapy with an immune checkpoint inhibitor called nivolumab.
Immunotherapy to Treat Patients With Acute Myeloid Leukemia
This grant will provide expanded support for two ongoing clinical trials in acute myeloid leukemia (AML), a cancer that occurs in more than 62,000 people annually and affects the blood-forming cells in the marrow. The trials explore the combination of a more tolerable anti-leukemia drug, decitabine (DAC), given with a new targeted antibody that has been shown in preclinical testing to improve the immune system’s natural ability to recognize and eradicate cancer cells. This grant will help conduct studies to launch future studies combining decitabine and cellular therapies.
New Targeted Therapies for Thyroid Cancer
Thyroid cancer is the ninth most common cancer in the United States, but there is no curative treatment available for patients with subsets of the disease that have spread to other parts of the body. OSUCCC – James researchers have shown that two different targeted therapies, given alone or in combination, are effective for treating a subset of advanced papillary thyroid cancer patients with BRAF gene mutations. This grant will fund evaluation of patient tumors and blood to learn how cancer cells become resistant, which will guide research to help improve treatment.
Combining Radiation and Immunotherapy to Treat Brain Tumors
Glioblastoma is the most common primary adult cancer affecting the central nervous system, and treatment outcomes are very poor. Scientists believe that a variety of mechanisms prevents the immune system from eradicating these tumors. In this project, researchers will test the effectiveness of radiation with immune modulating treatments in a clinical model to identify potential ideal combination therapeutic strategies. This may lead to an optimal approach for translating these findings to human clinical trials.
Understanding Genetic Predisposition to Acute Myeloid Leukemia
Investigator: Clara D. Bloomfield, MD, College of Medicine (Internal Medicine), OSUCCC – James Leukemia Research Program, and Albert de la Chapelle, MD, PhD, College of Medicine (Cancer Biology and Genetics), OSUCCC – James Molecular Biology and Cancer Genetics Program
Differences in a person’s DNA make each person unique. These differences can also make individuals more susceptible to developing diseases like cancer. This study is aimed at discovering genetic differences that exist in the general (non-cancer patient) population that make people more susceptible to acute myeloid leukemia (AML). This information will help scientists better understand inherited risk of the disease to improve overall understanding of biologic causes of leukemia and inform future clinical practice.
2017 Winter/Spring Idea Grants
Understanding Potential Protective Effect of Female Hormones in Melanoma
Investigator: Craig Burd, PhD, College of Arts and Sciences (Molecular Genetics), OSUCCC – James Molecular Carcinogenesis and Chemoprevention Research Program
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
Investigator: Ramesh Ganju, PhD, College of Medicine (Pathology), OSUCCC – James Molecular Biology and Cancer Genetics Research Program
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 inefficient swallowing as well as airway safety 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
Investigator: Tatiana Oberyszyn, PhD, College of Medicine (Pathology), OSUCCC – James Molecular Carcinogenesis and Chemoprevention Research Program
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 and determine 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
Investigator: Emanuele Cocucci, MD, PhD, College of Medicine, OSUCCC – James Leukemia Research Program
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
Investigator: Qianben Wang, PhD, College of Medicine (Cancer Biology and Genetics), OSUCCC – James Molecular Carcinogenesis and Chemoprevention Research Program
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
Investigators: Clara Bloomfield, MD, Albert de la Chapelle, MD, PhD, College of Medicine (Internal Medicine, Cancer Biology and Genetics), OSUCCC – James Leukemia Research Program, and Molecular Biology and Cancer Genetics Research Program
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.
2016 Summer Idea Grants
Image-Guided, Catheter-Delivered Radiotherapy to Treat Low-Risk Prostate Cancer
Investigator: Michael Tweedle, PhD, College of Medicine
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
Investigator: Bhuvaneswari Ramaswamy, MD, College of Medicine
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.
Using Herpes Virus to Train Immune System to Destroy Cancer Cells
Investigator: Jianhua Yu, PhD, College of Medicine
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.
3-D View of Micro-Environment To Study Development of Advanced Cancer
Investigator: Jonathan Song, PhD, College of Engineering
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
Investigator: Monica Venere, PhD, College of Medicine
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
Investigator: Sameek Roychowdhury, MD, PhD, College of Medicine
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
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 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
Investigator: Denis Guttridge, PhD, College of Medicine, Michael Ostrowski, PhD, 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 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.
2015 Spring/Summer Idea Grants
Herpes-Based Virus to Attack Solid Tumors
Investigator: Tim Cripe, MD, PhD, College of Medicine and Nationwide Children’s Hospital
This team will test a new therapy for treating childhood and young-adult cancer. Oncolytic virus therapy uses live viruses to selectively infect and kill cancer cells, with minimal damage to normal tissue. Once in cancer cells, the anticancer virus is designed to kill cancer cells as it replicates and spreads to adjacent tumor cells. The goal is more complete and precise treatment of the tumor. This Pelotonia Idea grant will support a first-in-human study of a locally developed oncolytic virus based on the herpes simplex virus-1. Part of the Translational Therapeutics research program, this study is the first step toward determining whether the virus can shrink solid tumors outside the central nervous system.
Tumor-suppressor genes protect cells from developing into cancer. When these genes are mutated or silenced they can no longer protect the cell and this contributes to cancer development. Fhit is a tumor-suppressor gene that is lost in most human cancers, but scientists do not completely understand how or why its loss contributes to cancer development. In this study, researchers with the OSUCCC – James Molecular Biology and Cancer Genetics Research Program will identify Fhit-regulated genes that control cell survival, proliferation and invasiveness with the goal of identifying new targets for drugs that might help treat more than 50 percent of all cancer cases.
Improving Chemotherapy Effectiveness in Breast Cancer
Investigator: Alo Ray, PhD, College of Medicine
Many kinds of chemotherapy kill cancer cells by damaging the DNA of rapidly dividing tumor cells. At the same time, some cancer cells survive the treatment due to their ability to repair DNA damage and their use of checkpoint signaling pathways. This study examines ways to disrupt or block DNA repair and cell-signaling pathways that enable cancer cells to survive chemotherapy and radiotherapy treatments that are designed to kill them. Specifically, it could define whether blocking a certain signaling pathway in the presence of chemotherapeutic agents could improve chemotherapy effectiveness in breast cancer. This study is also supported by the Stefanie Spielman Fund for Breast Cancer Research.
Stem cells are cells that give rise to other cells in a tissue. A small proportion of cancer cells also have qualities of stem cells and are thought to play an important role in cancer development and resistance to chemotherapy. Leukemia-generating stem cells are widely accepted in myeloid leukemia, but little is known about the role of leukemia stem cells in the most common form of adult leukemia, CLL. In this study, researchers will evaluate a new technology for identifying potential stem-like CLL cells, determining whether they are true leukemia stem-like cells, and then learning more about their biology. The findings could lead to new and more effective treatments for CLL. The study is part of the OSUCCC – James Leukemia research program.
Male hormones, such as testosterone, are known as androgens. Decades of research have demonstrated that androgens are necessary for the development and progression of prostate cancer. In addition, antiandrogen hormone therapy has been a critical intervention in prostate cancer treatment. Although dramatic responses are often seen, the antiandrogen therapy ultimately fails as the cancer evolves to a treatment-resistant state. Exactly how androgens stimulate cancer growth and how resistance to antiandrogens occurs is poorly understood. The proposed research of this study — which is based in the Molecular Carcinogenesis and Chemoprevention research program — will provide a more precise understanding of the molecular and genetic events involved in these processes while helping to define markers that enhance our choices of antiandrogens for patients. This enhanced knowledge could result in the identification of androgen regulated targets and the development of more precise treatment approaches in prostate cancer.
Stem Cells’ Role in Brain Tumor Development and Spread
Investigators: Susan Cole, PhD, College of Arts & Sciences, Ichiro Nakano, MD, PhD, College of Medicine
Gliomas are the most common tumor of the central nervous system and are difficult to treat, resulting in overall poor treatment outcomes. Researchers with the OSUCCC – James Translational Therapeutics and Molecular Biology and Cancer Genetics research programs believe that populations of cancer stem-like cells cause these tumors to be resistant to therapy. This project will take a closer look at the tumor microenvironment and cell communication pathways that support these clusters of stem-like cells in an effort to better understand how regulating these pathways could lead to future treatment modalities in glioma.
Human papillomavirus (HPV) vaccination in young adults age 18 to 26 is an effective strategy for reducing the burden of HPV-associated diseases like cervical cancer, however, vaccination rates are suboptimal among this population. In a new pilot study, researchers with the OSUCCC’s Cancer Control research program — in collaboration with the Wilce Student Health Center — will test a mobile health intervention to communicate with young adults about HPV-associated diseases and the HPV vaccine in an effort to increase vaccination rates in this high-risk population.
2014 Spring Idea Grants
Delivering an AML Drug in Nano-sized ‘Fat Bubbles’
Title: CD-33-Targeted Liposomal Bortezomib (aCD33-L-BZT) for AML Therapy
Principal Investigators: Robert Lee, PhD, and Andrienne Dorrance, PhD
Acute myelogeneous leukemia (AML) affects more than 14,500 Americans annually and has a poor survival rate. The drug bortezomib has potential to help AML patients, but it is only weakly effective against leukemia in its current form. In this project, an OSUCCC – James team from the colleges of engineering, medicine and pharmacy will develop a novel delivery system for this medication by packing the drug into nano-sized bubbles of fat and attaching it to a homing device that seeks out leukemia cells, sparing healthy cells. Preliminary studies suggest this approach effectively targets leukemia cells and results in lower drug toxicities. Data from the study will determine whether this approach is suitable for testing in humans.
Social Isolation’s Role in Breast Cancer Development and Progression
Title: Social Modulation of PTEN in Women
Principal Investigators: Courtney DeVries, PhD, Maryam Lustberg, MD, Cynthia Timmers, PhD
Studies show that women with breast cancer who are socially isolated have worse clinical outcomes. This OSUCCC – James team will examine whether loneliness and isolation alter cancer-related gene activity in breast tissue. The study investigates a molecular mechanism by which the social environment influences breast cancer initiation and progression. The team hypothesizes that a tumor-suppressor gene called PTEN plays a significant role in this process. Information from this study could reveal potential new diagnostic, therapeutic and prognostic tools for breast cancer prevention and treatment. Breast tissue for this study will be obtained from women undergoing biopsy at the Stefanie Spielman Comprehensive Breast Center for possible breast cancer.
Mental Health, Stress and the Response to Cancer Treatment
Title: Psychological and Inflammatory Responses in Relapsed and Refractory Patients with Chronic Lymphocytic Leukemia (CLL) Undergoing Ibrutinib Therapy
Principal Investigators: Amy Johnson, PhD, Barbara Andersen, PhD
Chronic lymphocytic leukemia (CLL) is the most prevalent form of adult leukemia and is currently incurable. This project will assess stress, depression and quality of life in patients receiving an effective new treatment called ibrutinib, which has been studied extensively in clinical trials at The OSUCCC – James. This study examines the relationship between cancer growth factors and patient psychological function. This information could help physicians make treatment decisions by identifying patients at risk for poor outcomes.
Biomarker-Based Two-Drug Therapy for Acute Myeloid Leukemia
Title: Phase I Study of AR-42 and Decitabine in Acute Myeloid Leukemia
Principal Investigator: Alison Walker, MD
Overall survival is low for both pediatric and adult patients with acute myeloid leukemia (AML) on standard chemotherapy. This study is a phase I (first-in-human) clinical trial to test a two-drug approach that could significantly increase remission in AML patients. Initial studies conducted at This OSUCCC – James, have shown that the drug decitabine is well tolerated in older AML patients and can achieve a 47 percent remission rate. Additionally, patients with higher levels of a substance in the blood called miR-29b had a better response to decitabine than those with lower levels. A second drug, known as AR-42, which was developed by OSUCCC – James researchers, increases levels of miR-29b in leukemia cells. This clinical trial will administer AR-42 first to AML patients as a way to increase miR-29b levels in the blood and possibly improve the effectiveness of decitabine therapy. The findings evaluate an innovative strategy for increasing the number of AML patients who achieve complete remission.
Studying Health Disparities in 100,000-Underserved in America
Title: Cancer Disparity Research Network (CDRN) Cohort Feasibility Study
Principal Investigators: Electra Paskett, PhD, Peter Shields, MD, Mira Katz, PhD, Paul Reiter, PhD, Eric Seiber, PhD, Mike Pennell, PhD
Despite an overall decrease in cancer incidence and death in many populations, significant health disparities exist in low income, racial and ethnic minority, rural, immigrant, under and uninsured and low-educated populations. This project will establish a cohort of 100,000 underserved people to better understand the causes of cancer disparities in the United States. The cohort will focus on four underserved population groups that studies have shown suffer from disparities: African Americans, Appalachians, Asians and Hispanics. This grant will support the formation of a coordinating center to collect and analyze data and biospecimens from The OSUCCC – James network of collaborating recruitment sites across the United States.
Targeting Oncogenes for New Liver Cancer Drugs
Title: Development of Novel Therapeutics Against Hepatocellular Cancer in Preclinical Models
Principal Investigator: Kalpana Ghoshal, PhD
Liver cancer is the third leading cause of cancer death in the United States and incidence rates are rising. The liver is designed to keep foreign substances out of the body, so developing drugs that effectively penetrate the liver and successfully target cancerous cells has been challenging. In this study, researchers will conduct preclinical tests to determine the effectiveness of new drugs that target two oncogenes—genes that promote cancer growth when highly expressed—along with a tumor-suppressing microRNA called miR-122, which is critical to maintaining normal liver function. Results from these studies could lead to a phase 1 clinical trial in liver cancer patients.
Understanding Molecular Crosstalk Driving Aggressive Breast Cancers
Title: Role of Slit in CXCR4-Mediated Breast Cancer Metastasis
Principal Investigator: Ramesh Ganju, PhD
Research suggests that two molecular pathways in particular play important roles in breast cancer development and how it is spreads, but little is known about the molecular conversations and the chain of events that lead to breast cancer growth and metastasis. A better understanding of this molecular crosstalk could help scientists identify points in the pathway to intervene and put the brakes on cancer development. This project seeks to further characterize the role of proteins in the two targeted pathways to better understand breast cancer growth, blood vessel formation and tumor spread. This information is especially critical for the development of new therapies in triple-negative breast cancers.
Brain Inflammation and Depression and Anxiety in Breast Cancer Patients
Title: Randomized Placebo Controlled Study of Minocycline for Amelioration of Chemotherapy Induced Affective Disorders (OSU 13165)
Principal Investigator: Courtney DeVries, PhD, and Maryam Lustberg, MD
Breast cancer survivors commonly experience depression and anxiety—particularly when undergoing chemotherapy. Inflammatory changes in the brain could be a primary cause of these symptoms. This OSUCCC – James team will study whether reducing inflammation in the brain using a readily available and well-tolerated drug called minocycline reduces depression and anxiety during chemotherapy. This study will be conducted in up to 30 postmenopausal women receiving chemotherapy for breast cancer at the Stefanie Spielman Comprehensive Breast Center.
Digital Image Analysis, Targeted Therapies for Glioblastomas
Title: Defining Molecular Events for Targeted Therapy in Glioblastoma Using Digital Image Analysis
Principal Investigators: Metin Gurcan, PhD, Jose Otero, MD, PhD, Brad Elder, MD, Vinay Puduvalli, MD, Jessica Winter, PhD
Glioblastomas are the most common and deadly of primary brain tumors. Despite aggressive treatment, glioblastoma patients live an average of 15 months. In this project, OSUCCC-James researchers are developing advanced image analysis techniques to help guide critical decisions in patient treatment before and after brain surgery. This technology could also guide personalized treatment options, based on the specific molecular characteristics of each patient’s tumor. Current imaging technologies make it difficult to distinguish between a cancer recurrence and treatment affected by chemotherapy and radiation. The goal of this study is to determine whether computerized image analysis combined with advanced protein analysis can significantly improve diagnostic accuracy and identify potential biomarkers that might help personalize treatment for each patient and provide insights into drug resistance.
Tackling Treatment-Resistant Prostate Cancer
Awardees: Qianben Wang, PhD; Steven Clinton, MD, PhD
When prostate cancer returns after surgery, it often no longer responds to drug treatment. For this study, OSUCCC – James researchers will use Pelotonia funds to identify genes that treatment-resistant prostate tumors need to grow and that could be potential new targets for prostate cancer drugs. The findings could lead to new treatments for prostate tumors that currently have no effective therapy.
Preparing for Resistance
Awardee: Sameek Roychowdhury, MD, PhD
Cancer happens in part because changes in certain genes cause cells to grow and divide when they shouldn’t. One of these genes is called the fibroblast growth factor receptor (FGFR). Researchers at the OSUCCC – James have designed a phase II clinical trial to test a new drug, called ponatinib, which inhibits hyperactive FGFR genes. However, cancer cells often develop resistance to the drugs that are used to treat them. Anticipating that resistance might develop in some patients during the ponatinib trial, the researchers have received a Pelotonia grant that will enable them to collect biopsy samples from each trial participant’s tumor before and after treatment. The grant will also enable the researchers to sequence 20,000 genes in each sample and look for new gene changes that could cause ponatinib resistance. The findings will provide a foundation for further research on how cancer cells become resistant to FGFR inhibitors and for the development of drugs to counter the resistant cells.
A Plant Component That Might Help Immune Cells Control Cancer
Awardee: Jianhua Yu, PhD
A Pelotonia grant is enabling an OSUCCC – James researcher to learn whether a substance from edible plants boosts the cancer-cell killing activity of a type of immune cell. The Pelotonia-funded study will investigate the ability of the plant substance, called phyllanthusmin C (PL-C), to stimulate the activity of natural killer (NK) cells. Ultimately, the researchers hope to show that PL-C in the diet will help NK cells control acute myeloid leukemia and perhaps other cancers.
Probing a New Target in Triple-Negative Breast Cancer
Awardees: Robert Brueggemeier, Harold Fisk, PhD; Chenglong Li, PhD; Pui-Kai Li, PhD; Yasuro Sugimoto
Triple-negative breast cancer (TNBC) is one of the most aggressive forms of breast cancer. It is defined by the absence of estrogen, progesterone and HER2 receptors. These molecules are targets for the drugs used to treat other forms of breast cancer. Without those targets, the usual breast cancer drugs are rendered ineffective, leaving no good treatments for TNBC. For this study, Pelotonia funding is enabling OSUCCC – James researchers to conduct laboratory studies to learn whether drugs that inhibit a molecule called Mps1/TTK are a promising treatment for TNBC and other aggressive forms of breast cancer.
A New Approach to Cervical-Cancer Prevention
Awardees: Paul Reiter, PhD, MPH; Mira Katz, PhD, MPH
Several types of human papillomavirus (HPV) cause cervical cancer and other types of cancer. Cervical cancer is largely preventable through regular screening, and current guidelines recommend that women ages 30-65 seek a Pap test and an HPV test every five years, or a Pap test every three years. But most women diagnosed with cervical cancer have had few or no Pap tests. One strategy for increasing the number of women screened for the virus is the use of HPV self-testing. Women collect samples by themselves at home and mail them in for testing. Self-testing might be particularly effective for screening women in underserved communities, such as Appalachia. For this study, OSUCCC – James researchers are using a Pelotonia grant to develop a pilot program for HPV self-testing among women in Appalachia who have undergone little if any cervical screening. The study will provide needed information about the value of self-testing for cervical cancer prevention.
Personalizing Multiple Myeloma Treatment
Awardees: Mitch Phelps, PhD; Ming Poi, Pharm D, PhD; Susan Geyer, PhD
In 2012, 5,000 patients with multiple myeloma, an incurable cancer of the blood, were treated using stem-cell transplantation plus high doses of a drug called melphalan. The drug kills the person’s cancer cells, and the transplant rebuilds the person’s immune system. The treatment often prolongs patients’ lives and stops progression of their disease. But patients show dramatic differences in this progression-free period – from six months to 12 years. One problem is that individuals don’t metabolize melphalan the same way, resulting in differences in toxic side effects and differences in effectiveness from patient to patient. For this study, researchers are using Pelotonia funds to begin developing a step-by-step procedure, an algorithm, to personalize melphalan dosing to maximize the killing of myeloma cells while minimizing the drug’s harsh side effects
A Wearable Guidance System for Better Cancer Surgery
Awardees: Ronald Xu, PhD; Michael Tweedle, PhD; Alper Yilmaz, PhD
Tools that could help surgeons determine where a tumor ends and healthy tissue begins, and that could help detect hidden cancer cells, could greatly reduce cancer recurrence rates and improve the long-term outcomes of patients after cancer surgery. This Pelotonia-supported project is an initial step in developing such a tool. It will help develop and test a guidance system worn during surgery to identify surgical margins and guide the removal of tumors. The proposed system – the collaborative brainchild of clinical and engineering faculty – includes a fluorescence imaging module, surgical scene-capturing module, Google glass and a host computer. Prior to surgery, a cancer-targeting dye is injected into the patient’s vein. This dye is picked up on the fluorescence camera and fused with background images of the surgical area. Two additional cameras then reconstruct a 3-D topography of the surgical cavity and track the position of the surgical tool. Tumor margin and location information is further processed and projected to the Google glass, providing intraoperative imaging guidance.
A ‘Psychological Biomarker’ for Predicting Chemotherapy Side Effects
Awardees: Charles Shapiro, MD, and Kristin Carpenter
There is great variability in the side effects breast cancer patients experience with chemotherapy, and it remains difficult to predict a patient’s experience following chemotherapy. Clinicians believe that optimism (a general expectation of favorable outcomes) and coping (an individual’s reaction to perceived harm or threat) influence cancer patients’ quality of life, levels of fatigue, depression and sometimes even disease-free survival. But no clinical trial has yet evaluated whether optimism or coping in women with early-stage breast cancer can predict patients’ sense of chemotherapy-related side effects or of their health-related quality of life during or after treatment. This Pelotonia grant supports a clinical trial designed to learn if there is a correlation between chemotherapy treatment and side effects that include fatigue, nausea, vomiting, sensory neuropathy, pain, depression and insomnia. It will investigate whether mechanisms by which optimism and coping might influence these chemotherapy side effects. The findings could provide initial evidence of a “psychological biomarker” for predicting chemotherapy side effects, and they could assist in planning a larger phase III trial to test behavioral or other interventions that might lessen side effects via changes in optimism or coping.
Reversing Drug Resistance in Ovarian Cancer
Awardees: Jeffrey Parvin, MD, PhD, and David Cohn, MD
Chemotherapy kills cancer cells by damaging their DNA so badly that the cells cannot repair it. Nonetheless, ovarian cancer recurs in up to 80 percent of patients after treatment with chemotherapy. These OSUCCC – James researchers have found that a protein called histone deacetylase 10 (HDAC10) is part of an important DNA repair system in cells. They believe that this repair system allows some ovarian cancer cells to survive the damage inflicted by the platinum-based chemotherapy used to treat the disease. This Pelotonia grant will enable the investigators to examine whether drugs called HDAC inhibitors will knock out the HDAC10-powered DNA repair system and make drug-resistant ovarian cancers respond once more to platinum-based chemotherapy. If successful, the project will lay the groundwork for a new treatment strategy that might prolong the lives and reduce the suffering of women with ovarian cancer.
Arresting a Gene That Might Drive Esophageal Cancer
Awardees: Zui Pan, PhD; Tong Chen, MD, PhD
Esophageal cancer is the sixth leading cause of cancer death worldwide, largely because a large majority of cases are diagnosed at late stages of the disease. Research is needed to identify biomarkers for detecting the disease early and to develop new therapies for the disease. Studies by OSUCCC – James scientists have shown that a gene called Orai1, which helps regulate calcium levels cells, is present at abnormally high levels in esophageal cancer cells. The two researchers hypothesize that the hyperactive Orai1 gene causes abnormal changes in calcium levels in the cells and contributes to esophageal cancer progression and that inhibiting that over-activity could help control the disease. Their Pelotonia grant is enabling them to conduct experiments that will reveal more about the role of this gene in esophageal cancer and help them obtain larger grants for studies to learn whether drugs that target Orai1 would improve the treatment of esophageal cancer.
Targeting Two Genes Might Improve Melanoma Treatment
Awardees: William Carson III, MD; Albert de la Chapelle, MD, PhD; Kathrin-Ann Eisfeld, MD
Melanoma, the most deadly skin cancer, accounts for 75 percent of all skin cancer deaths in the United States, and its incidence is rising. Nearly 77,000 new melanoma cases were diagnosed in the nation in 2013. About 40 percent of all melanoma patients have a specific mutation in a gene called BRAF. The gene mutation also increases the likelihood that the cancer will spread to other parts of the body. Drugs have been developed that target mutated BRAF, but they work only in a subset of patients, most of whom ultimately become resistant to the drugs. This study uses Pelotonia funds to investigate BRAF-mutated melanoma and the role of a gene called microRNA-3151, a gene whose importance was discovered at the OSUCCC – James. The team’s initial data suggests that melanoma tumors that have mutated BRAF might respond better to BRAF inhibitors if microRNA-3151 is inhibited at the same time. This project will explore the mechanism of action of miR-3151 and evaluate whether BRAF-inhibiting drugs might more effectively treat melanoma when combined with inhibitors of miR-3151.