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.
Summer 2014 Pelotonia Idea Grants
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; Craig Hofmeister, MD; 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.