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The Better Than Ever (BTE) training program is a fitness training and fundraising program designed to help people make walking, running or biking a regular part of their lives. The program also raises funds to support pilot projects focusing on breast and gynecologic cancers at The University of Arizona Cancer Center. We are very grateful for the support of our BTE program members.
Each year, the BTE Scientific Review Committee, led by Setsuko K. Chambers, MD, chooses recipients for these grants. The total grant distribution for 2011 is $100,000. We are pleased that this year’s awards bring the 11-year grant distribution total to more than $1.7 million.
Investigating hypoxia in ovarian cancer using Hypoxyprobe(™)-1, a diagnostic biomarker for guiding hypoxia-targeted therapies
Hypoxia, a deficiency in the amount of oxygen reaching the tissues, is a common feature of many solid tumor types and is strongly associated with aggressive disease and chemotherapy and radiation resistance. The incidence of hypoxia in ovarian tumors has not been widely investigated.
In tumor tissues obtained from patients participating in this study, the investigator will assess the percentage of ovarian tumor cells that are growing in hypoxic conditions by using an investigational diagnostic chemical probe called Hypoxyprobe(™)-1. These results will be compared with a molecular biomarker of hypoxia called HIF-1α. The information gained from this new BTE study will provide evidence to guide the clinical investigation of hypoxia-directed therapies in ovarian cancer. The tumor tissue obtained as part of this study will also be a valuable resource for investigating how hypoxia contributes to traditional chemotherapy resistance.
2010
In 2010, the five grants involved testing novel therapies, understanding biological processes, developing innovative diagnostic tools and using gene expression signatures to predict treatment response. The diseases of focus are ovarian cancer, cervical cancer and breast cancer.
Shona T. Dougherty, MB, ChB, PhD
Pro-apoptotic molecular therapy of ovarian cancer
This study will explore the therapeutic potential of a novel ovarian cancer treatment that exploits the secretion by tumor cells of a particular soluble molecule. The molecule, known as vascular endothelial cell growth factor (VEGF), plays an important role in the formation of the blood vessels that support tumor growth. Using genetic engineering techniques, we have generated an artificial receptor that causes cells to die upon binding of VEGF. A specially modified non-infectious virus will be used to introduce and express this receptor in ovarian tumors and the effect on tumor survival will be determined. Particular emphasis will be placed on ensuring that the approach is safe and that various normal cell types are not harmed as a result of treatment. Such studies are essential prior to the initiation of planned clinical trials.
Andrew R. Rouse, PhD
Confocal Microlaparoscope for Imaging the Fallopian Tube
Currently there is no way to detect early stage ovarian cancer and most cases are diagnosed at advanced stages when treatment options are limited and prognosis is poor. This study aims to develop a small and flexible endoscope that provides real-time cellular-level images of tissues inside the abdominal cavity. The device will image early-stage ovarian cancer on the surface of the ovary as well as inside the fallopian tube, where many ovarian cancers are thought to arise. Such a device would be used during a laparoscopic procedure to diagnose early-stage ovarian cancer and may provide an effective way to screen women at high risk of developing the disease.
Unraveling the Inhibitory Mechanisms of Bacitracin on HPV16 Infection
Human papillomavirus (HPV) infections are associated with more than 99 percent of all cervical cancers and therefore represent a significant cause of worldwide morbidity and mortality among women, especially in developing countries. Despite being the causative agents of cervical cancers, the molecular mechanisms involved in host cell invasion are poorly understood for oncogenic HPVs. We have observed that Bacitracin, an FDA approved antibiotic commonly available in over-the-counter ointments, blocks HPV infection perhaps by inhibiting a class of enzymes that may play a role in HPV-host cell invasion. Understanding the inhibitory mechanisms of this compound will expand our knowledge of HPV-host cell interactions and identify potential targets for the development of HPV antivirals and prophylactics.
Isolation and Gene Expression Profiling of Circulating Tumor Cells in Breast Cancer
Circulating tumor cells (CTCs) are rare cancer cells shed into the blood stream of breast cancer patients. In a prospective clinical study enrolling 120 newly diagnosed breast cancer patients, we will obtain a tube of blood and a small piece of tumor tissue from surgery. The purpose of our study is to determine if CTCs are cancer stem cells. We will use a novel technique we developed that permits isolating rare CTCs and studying their molecular biology. We will also study if a CTC gene expression signature may be defined for patients with locally advanced breast cancer that predicts for response to treatment. As CTCs may explain why disease recurs despite aggressive treatment of breast cancer, this novel approach has potential to determine if studying CTCs can help guide physicians in making treatment decisions for breast cancer patients.
Spectroscopic Photoacoustic Imaging of Molecular Expression in Metastatic Breast Cancer
Our long-term goal is to develop novel imaging tools and complementary contrast agents to noninvasively monitor the tumor microenvironment and improve treatment strategies for breast cancer patients. Because detection of just one cell surface receptor is generally an incomplete diagnosis of metastatic breast cancer, we will develop a photoacoustic imaging system and targeted contrast agents to simultaneously map expression of multiple surface receptors. This will dramatically enhance our existing pre-clinical imaging platform already capable of tracking a tumor’s growth and vascular network in three dimensions. Photoacoustic imaging is a safe, highly sensitive real-time technology that potentially provides powerful diagnostic and theranostic capability during routine ultrasound breast exams.
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