The Mayo Clinic
Rochester, MN
MAYO CLINIC PROSTATE CANCER PROGRAM
Donald J. Tindall, Ph.D.
Director of the Prostate Cancer Program
Mayo Clinic
Rochester, MN
The Mayo Clinic Prostate Cancer Program is grateful to the T.J. Martell Foundation for its generous financial support to combat prostate cancer.
The Mayo Clinic Prostate Cancer Program is structurally based on the close interactions and collaborations of the members of the Departments of Urology, Biochemistry and Molecular Biology, Immunology, Pharmacology, Laboratory Medicine and Pathology, Oncology, and Health Sciences Research. The primary objective of the Mayo Prostate Cancer Program is to enhance understanding of the biology of prostate cancer and to translate this new information into clinical application. This is accomplished by coordinating interdependent, cooperative research projects within the Mayo Prostate Cancer Program that are mutually reinforcing and that collectively maximize its translational research objectives. The unifying research themes of the Mayo Prostate Cancer Program are described below.
Mayo Clinic offers unique opportunities for collaboration and resources for the study of prostate cancer. This includes a large clinical population plus a multidisciplinary base of basic scientists, urologic surgeons, medical oncologists, radiation oncologists, pathologists, diagnostic radiologists, medical geneticists and epidemiologists who are truly interested and devoted to the study of prostate cancer. Most of the Mayo Prostate Cancer Program investigators are either part of or involved with other Mayo initiated research endeavors including the Mayo Comprehensive Cancer Center and the Tumor Biology Program. The Cancer Center programs include: Cancer Imaging, Cancer Prevention and Control, Cell Biology, Developmental Therapeutics, Gastrointestinal Cancer, Gene Therapy, Genetic Epidemiology & Risk Assessment, Hematologic Malignancies, Immunology & Immunotherapy, Neuro-Oncology, Prostate Cancer and Women’s Cancer.
One group of investigators has been testing the hypothesis that specific molecules in prostate cancer cells are able to interact with an important transcription factor, the androgen receptor, and inappropriately switch it on in the absence of androgen attachment. These investigators are currently performing detailed studies with three promising candidate molecules, termed p300, FHL2, and RIP140. They have data from human prostate cancer cell lines and human prostate tumor samples, which suggest that these molecules play a very important role in switching on the androgen receptor in the absence of androgens. This group is also testing the ability of a drug called dutasteride to prevent the androgen receptor from being switched on in non-cancerous prostate tissue, and thus prevent prostate cancer development in men at higher risk for developing the disease. They have been investigating in detail how the androgen receptor in its “on” form is able to promote the proliferation of normal and cancerous prostate cells, identifying a protein termed FOXO1 as a crucial factor. Armed with an ever-increasing understanding of the molecules that drive prostate cancer development and progression, they are testing ways to more accurately predict the course of disease, and designing approaches that could be used to treat or prevent prostate cancer.
Another group of investigators is combining its expertise in molecular biology, cell biology, genetics, clinical chemistry and the clinical management of prostate cancer patients to identify novel markers of prostate cancer and to develop assays for detecting these markers. Recently, the major focus has been to identify cohorts of patients, which can be used to validate these markers.
Yet others are investigating the potential of a novel imaging technique called vibro-acoustography for prostate imaging. Their preliminary studies have demonstrated that vibro-acoustography offers several key features that are important in the detection and treatment of prostate cancer. In particular, this method is sensitive to tissue stiffness, thus can be used to detect prostate tumors that are stiffer that the normal tissue. This method is also very sensitive to the presence of calcifications. It is expected that the performance of vibro-acoustography will be superior to that of conventional trans-rectal ultrasound imaging with regard to detection of malignant lesions and with respect to some aspects of guiding minimally invasive prostate procedures. Current ongoing efforts in the development of a surface vibro-acoustic probe for applications in breast cancer serve as important initial efforts from which this research in prostate imaging will benefit.
A different group of investigators is studying a novel method of killing prostate cancer cells with radioiodine. These studies are a collaboration of investigators with widely varying background and expertise. One of our investigators has focused most of his career on thyroid diseases. He has considerable clinical experience in the use of radioiodine for therapy and diagnosis of thyroid diseases. He also has considerable experience in laboratory investigation involving thyroid cells, radioiodine, and thyroid molecular and cell biology, especially that involving thyroidal iodine uptake. As a logical extension of his thyroid focus, he has become interested in the potential use of the thyroidal iodide transporter as a potential therapeutic gene for therapy of non-thyroidal tumors because of its potential importance and because of the exciting success of his preliminary studies. A co-investigator on the proposal is a member of the Mayo Molecular Medicine Program and an expert in cancer gene therapy and vector development. Another co-investigator, an immunologist, is contributing expertise in the evaluation of the immune responses to radioiodine therapy of prostate cancer. Other investigators have also contributed to preliminary results through their expertise with prostate cancer cells and the PSA promoter. This rare collection of expertise and technology required for the conduct of these studies on a single campus makes Mayo's ability to perform them relatively unique.
Investigators are also collaborating on a study of the capacity of synthetic peptides to induce cytotoxic and helper T lymphocyte responses to prostatic-associated antigens as a means of developing specific immunotherapy for prostate cancer. It has been demonstrated that tumors can evade CTLs by masking their Major Histocompatibility Complex Class I molecules. Investigators at Mayo are characterizing the immune involvement in cell killing that is induced by their vector constructs and to determine the effect of androgens on this response.
Another group of investigators are developing a novel cellular vaccine for the treatment of prostate cancer. In collaboration with St. George’s Hospital Medical School, London, England, they are implementing clinical–grade manufacturing of the vaccine, design and performance of a clinical trial, immunological monitoring, and integration and combined interpretation of clinical and monitoring data for future refinement of the protocol.
These research findings will lead to a better understanding of the biochemical, molecular, immunological and genetic factors that regulate the initiation, progression and metastasis of prostate cancer cells. We feel confident that this research will translate into improved methods of detection, prognosis, treatment and prevention of prostate cancer. Results from these studies will provide a foundation for further collaborations within the Mayo community.
Funding from the T.J. Martell Foundation has been and continues to be critical to the success of our research efforts. Thank you for your generous commitment to the Mayo Prostate Cancer Program. |