For the second year, the Cincinnati Cancer Center (CCC) has awarded $160,000 in pilot grants to members and basic scientists who are collaborating to find out more about various cancers with hopes of generating more data and additional funding.
"This type of funding allows for more experimental concepts to be investigated, whereas federal agencies may not initially choose to support these high-risk, high-reward studies,” says Shuk-mei Ho, PhD, director of the CCC, Jacob G. Schmidlapp Chair of Environmental Health and professor at the University of Cincinnati (UC) College of Medicine. "We hope this support will launch the careers of junior colleagues while helping to expedite some novel research that could uncover new or better ways to study or treat cancers in addition to providing preliminary findings that could lead to federal funding opportunities and support the use of core facilities and shared physical space.”
Estrogen Receptors and MED1 in Breast Cancer Metastasis: $60,000
Xiaoting Zhang, PhD, associate professor in the Department of Cancer Biology and member of the CCC, along with co-principal investigators Elyse Lower, MD, professor in the Division of Hematology Oncology and director of the Comprehensive Breast Cancer Center within the UC Cancer Institute, and Jiang Wang, MD, PhD, associate professor in the Department of Pathology and Laboratory Medicine and member of the CCC, are studying MED1—a protein found in breast cancer cells that when eliminated is found to stop cancer cell migration and invasion—as a therapeutic target for metastatic breast cancer.
"We truly appreciate this timely and generous support for our basic scientist-clinician collaboration in the study of breast cancer, the most common type of cancer and a leading cause of death among women in the U.S.,” Zhang says. "Metastasis, a process in which tumor cells spread, is known to be the primary cause of death for breast cancer patients. Despite the fact that two-thirds of metastatic breast cancers express estrogen receptor and treatments such as estrogen blockers can sometimes shrink or slow the growth of metastatic tumors, resistance to these treatments often develops, and there is currently no cure for these cases.
"We recently discovered that MED1, a protein that directly interacts with estrogen receptors, is required for both resistance to estrogen blockers and tumor spread. MED1 is highly expressed and amplified in about half of human breast cancers, and recent studies have found an increased frequency of MED1 mutations in circulating tumor cells following anti-estrogen treatments. Using this funding, we hope to further investigate the role of MED1 in breast cancer metastasis and test the efficacy of a new treatment—an RNA nanotherapy—to specifically target MED1 and overcome both resistance to estrogen blockers and tumor metastasis.”
Metabolic Pathways Controlling Glucose Consumption in Kidney, Brain Cancer Cells: $60,000
David Plas, PhD, Anna and Harold W. Huffman Chair in Glioblastoma Experimental Therapeutics, and Maria Czyzyk-Krzeska, MD, PhD, both members of the Department of Cancer Biology and the CCC, will partner with Kenneth Setchell, PhD, and Lindsey Romick-Rosendale, PhD, from the Department of Pediatrics at the College of Medicine and Cincinnati Children’s Hospital Medical Center, and Patrick Limbach, PhD, of the Department of Chemistry in UC’s McMicken College of Arts and Sciences, to study the metabolism of kidney and brain cancer cells.
"One of the fundamental marks of cancer is increased glucose metabolism,” Plas says. "Brain and kidney tumors are deadly cancers that use glucose metabolism to grow and resist chemotherapy. We will investigate tumor suppressor control of glucose metabolism in these two cancers, identifying similarities and differences to help improve chemotherapeutic efficacy.
"Through our partnership integrating tumor model systems with expertise in new technology to study metabolism, or metabolomics, we hope to discover chemotherapeutic approaches that are directed at brain and kidney cell metabolism, while driving tumor metabolomics research across the CCC.”
Drug Co-Delivery Using Nanoparticles for Metastatic and Drug-Resistant Breast Cancer: $40,000
Joo-Youp Lee, PhD, associate professor in the Department of Biomedical, Chemical and Environmental Engineering in UC’s College of Engineering and Applied Science, along with co-principal investigators Yuet-Kin (Ricky) Leung, PhD, and Pheruza Tarapore, PhD, both assistant professors in the Department of Environmental Health and members of the CCC, are using the funding to study the use of nanoparticle drug delivery for treatment of metastatic and drug-resistant breast cancer.
"The development of nano-scaled carriers as a drug delivery system has made a tremendous difference in the fight against cancer,” Lee says. "Among these tiny carriers, various nanoparticles made of biocompatible and biodegradable materials have been the focus. Significant progress has been made in improving nanoparticle formulas, targeting and drug potency. However, despite these advancements, metastases and drug resistance remain major challenges.
"To address these technical challenges, we will use our funding to study the co-delivery of microRNA inhibitors that can effectively stop the protein transformation that promotes cancer progression as well as drug resistance and sensitize the cancer cells to chemotherapeutic drugs, effectively killing breast tumor cells. Initial studies from our lab show positive results in a pH-sensitive nanoparticle known as PLGA-PHis-PEG, which encapsulates microRNA inhibitors and chemotherapeutic drugs. With the funding, we will further examine the efficacy of our proposed nanoparticle-based co-delivery system for the targeted and controlled delivery of the microRNA-221/222 inhibitors and doxorubicin, a chemotherapy drug, to the breast cancer cell line MDA-MB-231 to hopefully prevent spread of cancer and drug resistance.”