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.