Research into preventing skin cancer and colorectal cancer, and preventing and treating pain from bone and other cancers will be supported by more than $19.5 million in grants recently received by University of Arizona Cancer Center members. The research funding supports more than 20 laboratory research and 27 staff positions. Among the major awards:
Chemoprevention of Skin Cancer
Since 1980, The University of Arizona Cancer Center has conducted research in skin cancer prevention with funding from the National Cancer Institute. The NCI recently renewed the Cancer Center’s Program Project Grant, awarding $6.9 million to continue funding drug development research for five years. Cancer Center Director and Regents Professor David S. Alberts, MD, and Timothy Bowden, PhD, Professor Emeritus Cellular and Molecular Medicine, Molecular and Cell Biology, Pharmacology and Toxicology, Radiation Oncology, and former UACC chief scientific officer, are the project’s co-principal investigators.
The goal of the grant is to develop small drug molecules for topical administration to treat severely sun-damaged skin and precancerous lesions, called actinic keratoses. More than 3 million cases of non-melanoma skin cancer occur annually in the United States.
“Our skin cancer prevention program project grant uniquely features the use of 'personalized medicine' methods to develop small, topically administered drug molecules to eradicate aberrant genomic changes in severely sun-damaged skin,” Dr. Alberts said.
In its 31-year history, the Chemoprevention of Skin Cancer Program Project Grant has developed several prevention agents that are in commercial development: myristyl nicotinate, invented by Elaine Jacobson, PhD, FACN; and Myron Jacobson, PhD, both professors of pharmacology toxicology and being developed by Niadyne Pharma, Inc., of Tucson; and melanotan, invented by Robert Dorr, PhD, RPH, professor of pharmacology; Victor Hruby, PhD, Regents Professor of chemistry and biochemistry, and the late Mac Hadley, PhD, a biology and anatomy professor, and developed by Clinuvel Pharmaceuticals, Ltd., of Melborune, Australia. The program has other agents in various stages of development. The UACC’s skin cancer prevention program has been awarded more than $67 million since it was originally funded.
Selenium Colorectal Cancer ChemopreventionTrials
A $4.9 million grant from the NCI will fund novel randomized controlled trials to measure the effect of the dietary mineral supplement selenium in preventing colorectal adenomas (polyps) and advanced colorectal adenomas, the benign precursors to most colorectal cancers. Colorectal cancer is the second most-common cause of death from cancer in men and women combined, accounting for almost 50,000 deaths annually. The study also will determine if selenium supplementation increases risk for pre-diabetes or Type 2 Diabetes.
The study will be led by Peter Lance, MD, FRCP, the UACC’s Chief Cancer Prevention and Control Officer and Professor of Medicine, Molecular and Cellular Biology and Public Health, and Patricia Thompson, PhD, co-leader of the Cancer Prevention and Control Program and an Associate Professor of Cellular and Molecular Medicine. Dr. Lance’s medical specialty is gastrointestinal cancers. Dr. Thompson’s research expertise is the development of biological markers of human disease and their application, with an emphasis on colorectal cancer.
Study collaborators from the Mel and Enid Zuckerman College of Public Health include Professor Denise Roe, DrPH (Biostatics); and Associate Professors Elizabeth Jacobs, PhD (Epidemiology), and Paul Hsu, PhD (Biostatistics).
While most adenomas can be removed by a colonoscopy, Dr. Lance said 20 to 50 percent of individuals undergoing a repeat colonoscopy three to five years later have new adenomas. He, Dr. Thompson and their team will study whether treatment with selenium yeast for three to five years will reduce the rate of recurring adenomas without serious toxicity. Initial research into the effectiveness of selenium on polyp recurrence was done though The University of Arizona Cancer Center’s colon cancer prevention program project grant.
Preventive Analgesia for Bone Cancer Pain and Metastatic Prostate Cancer-induced Pain
Pharmacology Professor Patrick Mantyh, PhD, JD, was awarded two NCI grants totaling $3.1 million to test if tumors and their associated stromal cells release a growth factor that induces nerve fibers to reorganize and drive bone cancer pain, experienced by people whose breast, prostate or lung cancer has metastasized into their bones.
“Data generated from this project has the potential to fundamentally change our understanding of the mechanisms that drive bone cancer pain and promote the use of preventive analgesia which may block the development of severe bone cancer pain,” Dr. Mantyh said.
Prostate cancer spreads to various organs, but its spread to the bone is frequently the only detectible site of the metastasis. Dr. Mantyh’s second research project focuses on understanding the mechanisms that drive prostate cancer-induced bone pain to develop therapies that can better treat this chronic pain.
Dr. Mantyh’s research interests are in cancer, cancer pain and non-malignant bone pain, stem cells and skeletal health in disease and aging.
Investigation of an Anti-cancer Phytochemical Targeting Nrf2
Pharmacology and Toxicology Associate Professor Donna Zhang, PhD, will apply a $1.55 million grant to her work developing a novel antioxidant compound that has proven its ability to combat chemoresistance and enhance the efficacy of current chemotherapeutic drug, a breakthrough in the effectiveness of cancer treatment.
The key to the discovery is an understanding of the transcription factor, or movement of genetic information of the protein Nrf2. Nrf2 regulates a multitude of genes that promote cell survival under detrimental environments, such as oxidative stress.
Oxidative stress is associated with an imbalance between the production and removal of chemically reactive molecules containing oxygen known as reactive oxygen species. During times of oxidative stress, the body's ability to detoxify and repair damage is disrupted and has been implicated in cancer and other diseases.
The ability of cells to properly regulate the Nrf2 defense response is important to protect against the damaging effects of oxidative stress.
Human Prostate Cancer Metastasis and Laminin binding Integrins
Cellular and Molecular Medicine Professor Anne E. Cress, PhD, will continue her prostate cancer metastasis research with a $1.54 million NCI grant.
Early – and often clinically unapparent – bone metastasis can provide a sanctuary site for tumor cells and occurs in prostate, breast and lung cancers. Current chemotherapy agents do not work well at preventing or treating bone metastases. Unfortunately, this occurs early in disease progression and may explain the clinical reality of widespread recurrence as aggressive metastatic disease five to 10 years after initial detection, Dr. Cress said.
Dr. Cress’ collaborator on this grant is Isis Sroka, PhD, a Research Assistant Professor of Pharmacology and Toxicology.