CINCINNATI—Marlene Harris-Ride Cincinnati has continued its support of University of Cincinnati Cancer Institute scientists with the annual award of five grants, totaling $200,000, to continue promising breast cancer research.
Ride Cincinnati, a cycling event for all ages and abilities, was founded in 2007 by Harvey Harris, DDS, his family and two friends in memory of his late wife, Marlene Harris.
Ride Cincinnati has contributed $828,000 directly to the university since August 2007. In addition, the Western & Southern Foundation has earmarked $214,307 from its gifts to the Barrett Center to support the Ride Cincinnati annual cycling event. The efforts to date have resulted in over $1 million for cancer research.
"It’s partners like this that help make the UC Cancer Institute a success,” says William Barrett, MD, director and associate director of education and community outreach at the institute, chair of the department of radiation oncology at the UC College of Medicine and medical director for UC Health’s Barrett Center. "Without this important funding, which is used for everything from hiring lab staff to purchasing supplies to actually running the experiments, some of these important findings would never be discovered.”
This year’s winners, who were each awarded $40,000, include:
Kim Cecil, PhD, a professor in the UC’s department of radiology and a spectroscopist within the Imaging Research Center at Cincinnati Children’s Hospital Medical Center, for "Proton Magnetic Resonance Spectroscopy: Predicting Neoadjuvant Chemotherapeutic Response.”
Determine the benefit of performing proton magnetic resonance spectroscopy (MRS) in women receiving neoadjuvant chemotherapy (therapeutic agents delivered before a main treatment) for breast cancer: Preliminary data shows that neoadjuvant chemotherapy response to therapy can be distinguished from non-response based upon decreases in choline concentrations in human tissue, as MRS provides a chemical measurement within the MRI examination. While promising, translation to routine clinical use has been limited by low sensitivity for the MRS technique. The primary problem is the low concentration of choline in breast lesions among the strong water and fat signals of in the breast tissue. Researchers developed a cutting-edge bilateral breast magnetic resonance coil with enhanced sensitivity, which should allow significantly improved detection of total choline, the primary marker of cell membrane turnover. The project will allow researchers to obtain vital preliminary data for a larger trial with sufficient size and scope to fully address the proposed hypothesis: MRS-measured choline concentrations can distinguish response from non-response in newly diagnosed breast cancer patients undergoing standard neoadjuvant therapeutic regimens.
David Plas, PhD, associate professor in the department of cancer biology, for "Evaluating S6K1 Inhibitors for Breast Cancer Therapy.”
Survey of S6K1 inhibitor actions in breast cancer: S6K1 has been found to increase the metabolism, translation and cellular growth in cancer cells. However, it has been surprisingly understudied as a therapeutic target in oncology. Using The Cancer Genome Atlas, a catalogue of genetic mutations in cancer, analysis revealed that amplification of the S6K1 gene is a frequent genomic alteration in breast cancer. Thus, S6K1 is a particularly promising target in breast cancer. Using cell lines that are representative of breast cancers with amplified S6K1, researchers will test different classes of inhibitors for the potential to improve chemotherapy for breast cancer.
Lisa Privette-Vinnedge, PhD, a research instructor in the department of pediatrics at the UC College of Medicine; Cincinnati Children’s, for "Defining the Role of DEK Oncogene in Breast Cancer Stem Cell Tumorigenicity and Pre-Clinical Testing of Therapeutic DEK Targeting Strategies.”
Understanding how breast cancer stem cells contribute to tumor formation and drug resistance and pre-clinical data to test the targeting of the DEK oncogene as a novel treatment option: One in eight American women will be diagnosed with breast cancer, and although survival has improved dramatically with early detection, many women with advanced, metastatic or recurrent, drug-resistant tumors succumb to the disease. Recurrent disease is thought to be caused by the presence of breast cancer stem cells which are drug resistant and can recreate a tumor from only a few cells that survive initial treatment. Detecting this small population is often beyond the limits of current medical imaging technology. As these cells are uniquely drug resistant, current treatment strategies inefficiently target this population, and novel therapies are required to target them. Previously published data has defined new roles for the DEK oncogene in promoting the transformation, drug resistance and metastasis in non-breast cancer stem cells cancer cells and has connected the Wnt/β-catenin pathway as the mechanism that causes the reactions. It has also been found that the DEK oncogene promotes the maintenance of the breast cancer stem cells. In this study, researchers will test the overarching hypothesis that DEK drives breast cancer metastasis and drug resistance specifically in the breast cancer stem cell population and through stem cell-associated molecular pathways and show that DEK is a therapeutically viable target in breast cancer stem cells. Using stem cell cultures and animal models, researchers will define the roles of DEK in breast cancer stem cell movement, with a focus on the involvement of the Wnt pathway, and drug resistance. Mass spectroscopy studies—an analytical technique that produces a "blue print” of the components of a sample of material—will identify new DEK modifications and protein interactions unique to breast cancer stem cells. Additionally, preclinical testing of two new gene-targeting therapeutics (a virus and an RNA interference nanoparticle) will be administered to see if they selectively target DEK expression. The hope is to determine if DEK loss limits tumor growth, improves the efficacy of current chemotherapies and eliminates the breast cancer stem cell population to help prevent recurrence.
Timothy David Struve, MD, a resident physician at UC Medical Center, for "A Novel Biomarker for Local Recurrence and Radiosensitivity.”
Identifying a biomarker for local recurrence of breast cancer: Locoregional recurrence, or local recurrence, of breast cancer after mastectomy, meaning cancer that comes back where it was originally detected, is associated with pain, psychological distress and increased risk of spread, or metastasis, with few treatment options. Post-mastectomy radiotherapy decreases the risk of recurrence and improves survival in node positive (cancer cells found in the lymph nodes) women following mastectomy. However, some woman can safely avoid this treatment and the risks that come along with it. Unfortunately, targeting the patients who will benefit from radiation has been difficult. A molecular marker that can predict local recurrence could help with identifying women who are more likely to develop local recurrence and will benefit from localized therapy, like post-mastectomy radiotherapy. In this study, researchers hope to identify this biomarker and think that dopamine receptor type 1 (D1R) overexpression in breast cancer is a marker of radiotherapy resistance and increased risk to this kind of recurrence. Using tissue specimens from women with breast cancer, researchers will attempt to determine if D1R expression correlates with local recurrence; they will also examine whether those women with increased expression of D1R had less benefit from radiotherapy after mastectomy. Additionally, they will examine whether D1R activation with a dopamine agonist, a compound that activates dopamine receptors in the absence of dopamine, called fenoldopam, improves radiosensitivity to breast cancer cells.
Susan Waltz, PhD, professor in the department of cancer biology, for "The Role of HGFL in Aggressive, Metastatic Breast Cancer.”
Finding the use of HGFL as a biomarker for breast cancer and determining whether blocking the function of this protein in breast cancer may be an effective strategy to inhibit tumor spread (metastasis): Hepatocyte growth factor like protein (HGFL) is a growth factor that binds to the Ron receptor (a tumor causing gene) and activates it. The Ron receptor is overproduced in about 50 percent of human breast cancers, and blocking this receptor is an area of active investigation as a new therapy for breast cancer patients. High levels of Ron and HGFL are correlated with increased tumor spread (metastasis) and poor overall survival in breast cancer patients. In addition, breast cancer cells forced to produce excess HGFL grow faster and spread extensively in animal models. Recent studies have shown that while the normal breast tissue does not make HGFL, many breast cancers produce this protein. These findings are striking, as HGFL was thought to be made mainly by liver cells which secrete HGFL at high levels into the blood. While these recent studies provide strong evidence for the development and use of therapies to target Ron and HGFL in breast cancer, no studies have examined whether HGFL may serve as a biomarker of aggressive breast cancers or how HGFL works in driving breast cancer development and metastases. Given the dramatic upregulation (or increased activity) of this protein in breast cancer cells, researchers have evidence that cancer cell-produced HGFL may be required locally (in the cell) to support breast tumor growth, metastasis and for the tumor to evade killing by the immune system. This study will test whether aggressive breast cancer development requires tumor cell-produced HGFL to prompt Ron activation in the tumor and its local microenvironment.
Annual Ride Cincinnati Cycling Event June 8
The 2014 Ride Cincinnati cycling event is scheduled for Sunday, June 8, 2014, at Sawyer Point in downtown Cincinnati. More than 2,000 people participated in the 2013 event, which raised more than $285,000 for local breast cancer research at the UC Cancer Institute and its affiliated adult cancer care facility, the UC Health Barrett Center. Learn more about Ride Cincinnati at ridecincinnati.org