2009-10 Grant Award Winners
Setsuko K. Chambers, MD; Patrick W. Mantyh, PhD, JD
A Model for Human Breast Cancer-induced Bone Pain
Breast cancer, more so than most solid tumors, has the predilection to metastasize to bone, resulting in bone pain, bone destruction and frequently bone fracture, all of which can severely impact the quality of life and functional status of the patient. The goal of this proposal is to develop the first preclinical model to explore the mechanisms and factors that drive human breast cancer-induced bone pain and breast cancer growth in bone. We will focus on therapies that target tyrosine receptor kinases which drive bone pain and metastases. This study fosters a unique collaboration between a physician/scientist (Chambers), who is both a clinician and a tumor biologist, and a neurobiologist (Mantyh) who studies and developed the first preclinical model of cancer pain. By having both these investigators focus on the same platform we have the potential to synergistically interact to develop novel and more effective therapies that control cancer pain and reduce the progression of cancer.
Vince Guerriero, PhD
A Paradigm Shift Leads to a New Treatment for Breast Cancer
Breast cancer is the most common malignancy for women throughout the industrialized world. In general, most individuals with cancer do not die from the tumor in the primary site, but rather from local invasion and/or distant metastasis. This research takes on the challenge of developing a new revolutionary treatment for primary and metastatic breast cancer. The hypothesis is that expression of a specific protein on the tumor cell surface protects these cells from the patients’ immune system and therefore protects the tumor from elimination. This hypothesis will be tested by blocking the specific protein on the tumor surface using another protein. This will allow an immune response to ensue, which will destroy the tumor. Using a protein that will bind specifically to the surface of tumor cells and remove inhibition of the immune system against those cells has far reaching implications in the development of new treatments for breast cancer.
Ana Maria Lopez, MD, MPH
Assessment of Clinical Efficacy Utilizing Telepathology for Paps
This study aims to use technology to improve the ability to detect premalignant cells, in the hope that cervical cancer may be prevented. Though cervical cancer is treatable - and when detected early, is curable - detection of premalignant disease is the most clinically-effective and cost-effective outcome. This study will assess the role and accuracy of telepathology - using telecommunication technology to transmit a digital image to a pathologist - in cervical cancer screening. By eliminating the need for glass slides, breakage and loss of clinical material would not be a concern. Further, as a digital image, the clinical material may be easily and rapidly transmitted electronically for primary or second-opinion reads, which may be of greatest benefit to women in underserved, rural or remote areas and in developing countries. Finally, the digitized images allow for the addition of annotations, which may facilitate communication between consultants and may be helpful with education.
Kimberly McDermott, PhD
The Role of Primary Cilia in Breast Cancer Progression
Cilia - membrane-enclosed organelles that project from the surface of a cell - are found on a number of cell types in the mammary gland including epithelial cells, the precursor cells of cancer. Mutations in genes involved in ciliary assembly and function cause abnormal cellular functions such as loss of cellular polarity, which is a hallmark of cancer progression. We hypothesize that loss of primary cilia causes loss of polarity in cancer cells. This study should provide significant advances towards our understanding of the events involved in initiation of breast cancer. Furthermore, results obtained from these studies can be applied to future studies focused on understanding how primary cilia can be used in unique strategies for diagnosis and treatment of breast cancer.
Mark Nelson, PhD; Todd Vanderah, PhD; Patrick Mantyh, PhD, JD
Control of Breast Cancer Bone Metastasis by CB2 Receptor Agonist
Bone is one of the most common sites of metastasis in human breast cancer. Bone metastases cause cancer-related pain, pathologic fractures, hypercalcemia, neurological defects and immobility, which severely affect the quality of life in breast cancer patients. Conventional therapies do not allow a curative outcome for breast cancer bone metastasis. Therefore, determining factors that regulate the growth of breast cancer in the bone microenvironment is essential for the development of novel therapeutics for bone metastasis. To accomplish our goals, outstanding investigators from the departments of Pathology and Pharmacology will utilize both preclinical and basic research studies to focus on the therapeutic effects of cannabinoid receptor 2 (CB2) agonist. These studies are sure to result in new modalities of treating breast patients with bone metastases with the possibility of being used in patients with other bone cancers.
Marlys Witte, MD; Baldassarre Stea, MD, PhD
Radiation Damage and Radioprotection from Lymphedema and Other Vascular Complications in Women’s Cancers: An In Vitro and Clinical Observational Study
Radiation therapy (RT) to a cancer mass, or to the area surrounding draining cancer-containing lymph nodes, is a commonly used and important component of current therapy for breast and other female pelvic cancers. Among acute complications is lymphedema, a hardened type of tissue fluid swelling that progresses over time and involves the arms, legs and surrounding tissues. Due to removal or obstruction of lymphatic vessels and lymph nodes, lymphedema is a common, disabling, lifelong problem that impairs functional status, diminishes quality of life and occasionally threatens both limb and life. This study seeks to retain RT’s value in curing early cancer and controlling more advanced disease while preventing or minimizing delayed RT complications including lymphedema by testing the effectiveness of amifostine, an FDA-approved radioprotective agent. This will lay the groundwork for a clinical trial of amifostine by establishing an accurate baseline of lymphedema incidence in patients with breast cancer and other female pelvic cancers undergoing RT at the Arizona Cancer Center. The potential impact of this translational project worldwide on survivorship and quality of life of the large number of patients who are at risk for lymphedema is substantial.
Wenxin Zheng, MD
Detection of Endometrial Serous Carcinoma in its Early Form or Precancer Stage
Endometrial cancers can be basically divided into two categories: non-aggressive and aggressive. The aggressive endometrial cancer constitutes the majority of cancer deaths in postmenopausal women and there is currently no good method to cure or control it. This project aims to detect the aggressive type of endometrial cancer in its early form or precancer stage using a non-invasive cytology-based immunoassay. Clinical detection in its early form or precancer stage will provide us an outstanding opportunity to control or even prevent the disease.