$160,000 in Cancer Research Pilot Grants Awarded to Promote Collaboration

The UC Cancer Institute has awarded four $40,000 research pilot grants to aid in the interaction and collaboration between basic scientific and clinical investigators and facilitate the translation of laboratory findings into clinical therapies. 

The one-year grants will help the formation of multidisciplinary projects that will develop new approaches in cancer research. 

The winning teams are:

Principal Investigator Scott Langevin, PhD, assistant professor in the Department of Environmental Health

"Epidermal Growth Factor Receptor and Down Stream Signaling as Biomarkers of Cetuximab Response in Squamous Cell Carcinoma of the Skin”

Other team members include Mario Medvedovic, PhD, Environmental Health; Trisha Wise-Draper, MD, PhD, Nooshin Hashemi Sadraei, MD, and John Morris, MD, all from the Department of Internal Medicine, Division of Hematology Oncology; Kevin Redmond, MD, and Brad Huth, MD, both from the Department of Radiation Oncology; Yash Patil, MD, from the Department of Otolaryngology–Head and Neck Surgery; and Keith Casper, MD, and Michelle Mierzwa, MD, former faculty members at UC who are now at the University of Michigan. 

"Non-melanoma skin cancer is the most common malignancy in the United States, with more than one million new cases each year, 15 percent of which are squamous cell carcinomas. Exposure to ultraviolet radiation, largely through sun exposure, is the largest known risk factor for this type of cancer. Squamous cell carcinomas tend to pop up in areas of the skin that are most exposed to the sun, especially in the head and neck region. While surgical removal can cure most cases, a small fraction of these cases are more aggressive, which are often accompanied by metastases, including spread to the nerves, lymph nodes, and in some cases to further parts of the body. Additionally, these cancers have a tendency to reoccur and tend to result in poorer outcomes, with a 5-year survival rate of around 70 percent. In mucosal head and neck squamous cell carcinoma—those arising in the lining of the mouth and throat— past trials showed a 10 percent improvement in control of the cancer at its original site and overall survival when the medicine cetuximab was added to radiotherapy. The addition of cetuximab to chemotherapy in these cancers showed further improvement in outcomes. For lung and colorectal cancer, randomized trials suggested that the overproduction of epidermal growth factor receptor, which is a receptor on the surface of cells in certain proteins, and Ras (protein) mutations can predict response to cetuximab. However, no biomarker has been found for routine clinical use to predict response to cetuximab in mucosal—relating to the mucus membranes—or cutaneous—relating to the skin—head and neck squamous cell carcinomas. We started an investigator-initiated Phase II trial of post-operative radiation and cetuximab use for squamous cell carcinoma of the head and neck, in which 12 patients are enrolled so far. Several studies have provided valuable data on the mutations of hundreds of mucosal head and neck squamous cell carcinomas; however, much less is known about the mutations of the cutaneous type of this cancer. Our study will establish the largest genetic sequencing study to date on advanced cutaneous head and neck squamous cell carcinoma, and, importantly, will be the only study embedded in a clinical trial with standardized therapy for patients, allowing for a study of patient response to a cetuximab and radiation treatment regimen based on the mutations of each individual tumor.”

Principal Investigator Stephen Zucker, MD, professor in the Department of Internal Medicine, Division of Digestive Diseases

"Use of Bile Salts for the Prevention of Colorectal Cancer”

Other team members include Gila Idelman, PhD, Division of Digestive Diseases, and Megan Vogel, graduate student, and Christopher Mayhew, PhD, and James Wells, PhD, of the Pluripotent Stem Cell Facility at Cincinnati Children’s Hospital Medical Center.

"Over 6 percent of the U.S. population will develop colorectal cancer, and nearly half of those affected will die from their disease. Since most colorectal cancers develop from pre-existing, initially-benign polyps, efforts at prevention have focused primarily on the detection and removal of these lesions. Although effective at reducing cancer risk, colonoscopy is costly and uncomfortable and has led to decreased rates of compliance and cost-effectiveness. To reduce reliance on invasive techniques, efforts have been directed at identifying drugs capable of preventing the development and/or malignant transformation of benign polyps. In initial studies, our group has demonstrated that oral administration of the bile salt taurocholate causes a marked reduction in polyp formation in animal models. The effects of taurocholate appear to be mediated through activation of the farnesoid X receptor (FXR), a transcription factor (protein that binds to DNA sequences to control genetic information delivery) that controls the production of several genes that regulate cell cycling, including cyclin D1. Based on these data, we propose that bile acids are inhibitors of colon tumor formation and may potentially be used as preventive agents. The proposed studies are designed to validate and extend these findings in lab-created intestinal organoids derived from human cells.”

Principal Investigator Laura Conforti, PhD, associate professor in the Department of Internal Medicine, Division of Nephrology and Hypertension 

"Role of the Tumor Microenvironment in Limiting Immune Surveillance in Cancer” 

Other team members include Trisha Wise-Draper, MD, PhD, who is also the co-principal investigator, Department of Internal Medicine, Division of Hematology Oncology; Ameet Chimote, PhD, postdoctoral fellow in Conforti’s lab; and  Nives Zimmermann, MD, Department of Pediatrics; Cincinnati Children’s Hospital Medical Center. 

"Despite improvement in cancer treatment, a need exists for new biomarkers that can predict targeted therapy benefits and cancer outcomes as well as new therapies with limited side effects. This project is designed to use the immune system for the development of new biomarkers and new therapeutic strategies in cancer. The immune system plays an important role in cancer where a strong infiltration of cytotoxic CD8+ lymphocytes, which are T cells (white blood cells) that kill cancer cells, into the tumor is associated with longer disease-free survival and improved response to therapy. This means immune therapies, like immune checkpoint inhibitors, which are used to harness the immune system to fight cancer cells, are revolutionizing the treatment of tumors. In addition, the immune system offers the possibility of developing new blood biomarkers due to abnormalities of circulating T cells of patients with tumors. Adenosine, an immunosuppressant, accumulates in solid tumors and it has been associated with tumor progression, increased chance of cancer spread and poor prognosis because it inhibits cell movement, cell toxicity and secretion of anti-tumor cytokines (proteins that are important in cell signaling) in tumor-infiltrating T lymphocytes. We have shown that the effect of adenosine in T cells is mediated by an ion channel (KCa3.1) which controls the influx of calcium ions necessary for cell movement and release of cytokines. In this study, we are attempting to see if adenosine concentrated in the tumor’s ‘microenvironment’ limits immune interference by preventing the infiltration of the tumor by circulating T cells and targeting certain ion channels and cellular processes.”

Principal Investigator Maria Czyzyk-Krzeska, PhD, professor in the Department of Cancer Biology "Mechanisms of Bone Metastases in Renal Cancer”

Other team members include Michael Archdeacon, MD, Chair of the Department of Orthopaedic Surgery, and Chia-Ying Lin, PhD, Department of Biomedical Engineering, College of Engineering and Applied Science. 

"Clear cell renal cell carcinoma accounts for two to three percent of all adult malignancies in the U.S., with about 60,000 to 65,000 new cases and 13,000 to 14,000 deaths annually, with the incidence steadily increasing. Renal cell carcinoma is kidney cancer that originates in the lining of a part of the small tubes in the kidney that transport waste molecules from the blood to the urine. Cancer that has not spread when diagnosis is made usually has good associated outcomes, but the overall survival for metastatic renal carcinoma varies from one to a little over two years. The most frequent sites of metastases are lung, bone, liver and brain. Bone metastases are associated with severe illness, more aggressive cancer and poor outcomes. Skeletal, mainly osteolytic lesions (a ‘punched out’ area of severe bone loss) result in fractures, surgical interventions, spinal cord compression and hypercalcemia (high calcium levels in the blood), which is also related to poorer outcomes. The existing methods of treatment include image guided radiotherapy and surgical removal of the metastases, which provides an overall improvement in cancer survival. However, these treatments often lead to bone marrow suppression and have numerous side effects. Thus, there is a need to develop new therapeutic approaches specifically targeting bone metastases of clear cell renal cell carcinoma. In this study, we will study tumor-initiating cells (cancer stem cells) from different renal cancer cell lines to  determine their ability to form metastases in bones in animal models. We believe that we will find that only some of these cell lines will contain cancer stem cells with the ability to form bone metastases. Using these cells, we hope to identify pathways that promote this action and be able to identify new targets for therapeutic approaches.”