Marlene Harris-Ride Cincinnati has continued its support of University of Cincinnati (UC) Cancer Institute scientists with the annual award of seven 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 over $2 million directly to the university since August 2007. In addition, the Western & Southern Foundation has earmarked funds from its gifts to the UC Health Barrett Cancer Center to support the Ride Cincinnati annual cycling event.
In addition to the research projects (described below), a $20,000 grant will be awarded to the REDCap program within the UC Cancer Institute, to assist with breast cancer data collection.
Mechanism and pharmacological control of human ADP-ribosyl-acceptor hydrolase 3:
In-Kwon Kim, PhD, assistant professor of chemistry, McMicken College of Arts and Sciences; $35,000
About the study: A team led by Kim is hoping to discover ARH3 (ADP-ribosyl-acceptor hydrolase 3) inhibitors as a way to target and treat certain breast cancers. ARH3 is an enzyme that regulates poly(ADP-ribose) polymerases (PARPs), whose inhibition by small molecules has shown promise in selective killing of certain breast cancers. However, PARP inhibitors can cause drug resistance and harmful side effects in patients. Researchers in this study are aiming to develop safe and effective alternatives to PARP inhibitors by focusing on ARH3.
Mechanisms of mutant HER3 signaling and therapeutic potential in breast cancer:
Joan Garrett, PhD, assistant professor of pharmaceutical sciences, James L. Winkle College of Pharmacy; $35,000
About the study: HER3 mutations can be oncogenic in thousands of cancer patients. Researchers will investigate the molecular mechanisms by which mutant HER3 promotes breast cancer progression and identify the best treatment strategies for patients with HER3-mutant breast cancer. HER3 mutations occur in about 2.5 percent of all solid tumors; these findings could result in enhanced treatment strategies to improve outcomes for patients with HER3-mutant cancer.
Breast Papilloma: A unique opportunity to investigate risk factors and outcomes:
Benjamin Hinrichs, MD, assistant professor of pathology and laboratory medicine; Elizabeth Shaughnessy, MD, PhD, professor of surgery; Susan Pinney, PhD, professor of environmental health, all UC College of Medicine; $35,000
About the study: Using a combination of data in the UC Health Electronic Health Records and the Fernald Community Cohort, researchers in this study will look at breast papilloma risk factors and outcomes to assess if breast papillomas may be related to the development of breast cancer. While most breast papillomas are benign, some are atypical, and over the last 10 years, there has been an increase in UC Health pathology examinations noting breast papilloma. After completing the study, researchers will have validated the breast papilloma diagnoses and identified risk factors in a one of the largest case-control studies ever conducted and will use preliminary data in a R01 grant application to the National Cancer Institutes and the National Institute of Environmental Health Studies.
Targeting RON-dependent glutamine metabolism in breast cancer:
Susan Waltz, PhD, professor of cancer biology; Tom Cunningham, PhD, assistant professor of cancer biology; Elyse Lower, MD, professor of medicine, director, UC Cancer Institute Breast Cancer Center, all UC College of Medicine; $20,000
About the study: Researchers hope to find the mechanism by which RON signaling raises glutamine metabolism within the tumor, which could be a potential target for disrupting the process and shrinking tumors. The metabolism of glutamine, an amino acid that is used in the biosynthesis of proteins, in the context of RON signaling (RON is a cancer causing enzyme) is seen to be overproduced in breast cancer cells, and reduced breast cancer cell sustainability is seen when glutamine is inhibited by blocking the activity of Gln synthetase (or GS, the enzyme responsible for glutamine production). These studies will help researchers gain additional knowledge of tumor metabolism, uncover potentially translatable therapeutic strategies for patients and generate a deeper basis for study of RON-mediated metabolic reprogramming.
Enhancer RNAs in breast cancer metastasis and therapeutic resistance:
Xiaoting Zhang, PhD, associate professor of cancer biology, UC College of Medicine; $35,000
About the study: A team led by Zhang will work to further understand the role and molecular workings behind MED1(a protein coding gene) and its regulation of certain RNAs using animal models and human samples. A key part of the study will involve nanotechnology. MED1 is a coactivator of estrogen receptor and is responsible in part for the development of cancer. It was found in previous studies to be a key mediator in anti-estrogen treatment resistance and spread of breast cancer. Additionally, MED1 is overproduced in 40 to 60 percent of human breast cancers. This study will help provide clarity about how it impacts newly identified small RNAs called enhancer RNAs.
RON expression in breast cancer progression:
Vinita Takiar, MD, PhD, assistant professor of radiation oncology; Susan Waltz, PhD, professor of cancer biology; and Elyse Lower, MD, professor of medicine and director of the UC Cancer Institute Breast Cancer Center, all UC College of Medicine; $20,000
About the study: Metastatic breast cancer kills 40,000 patients each year. RON is an enzyme that has been associated with breast cancer recurrence, the development of metastases and relatively worse survival. However, it is unclear whether the expression level of RON in the breast tumor tissue predicts for the development of metastasis or whether there is any relationship between RON expression within the breast tumor and the metastatic site. Researchers will analyze RON expression in primary breast tumors and in areas of metastatic spread in the same patient and correlate with clinical outcomes. This will improve understanding of the relationship between RON levels and breast cancer progression.