Genitourinary Disease Oriented Team (GU-DOT)
ProposalGlobal BenchmarksSpecific BenchmarksDOT Leaders
The BACKGROUND: UC Irvine’s Chao Family Comprehensive Cancer Center (CFCCC) is one of only 41 NCI-Designated Comprehensive Cancer Centers in the United States and the only one in Orange County. The GOALS of the Cancer Center’s Genitourinary Disease Oriented Team (GU-DOT) includes biomarker validation: markers from biospecimens that can be obtained non-invasively in order to predict and monitor the clinical behavior of prostate cancer. In addition, the investigation of the role of inflammation in the development of prostate cancer, particularly as it may involve chronic infection with retroviruses, stromal effects or survival signals derived from pro-inflammatory cytokines. And finally, the identification of natural products that may modulate the growth of prostate cancer cells through unusual signaling pathways such as the Wnt or the Insulin-like Growth Factors Receptor pathways.
PROPOSAL: The Genitourinary Disease Oriented Team (GU-DOT) will be a multi-disciplinary consortium comprised of UC Irvine investigators from the disciplines of radiology, pathology, molecular biology/biochemistry, epidemiology & biostatistics, urology and electrical engineering/computer science. The GU-DOT will engage investigators who have an interest in translational science, comparative effectiveness research in surgery, health care disparities, and drug discovery in prostate cancers. Additionally, the GU-DOT will encompass the Schools of Medicine, Biological Sciences, and Engineering. The GU-DOT will carry out clinical and translational research under the auspices of the Chao Family NCI-Designated Comprehensive Cancer Center.
The GU-DOT will have the following Translational Research programmatic components:
1. Prostate Cancer Prevention
2. Prostate Cancer Screening & Diagnostics (early disease)
3. Prostate Cancer Therapeutics
These components are highly relevant to prostate carcinogenesis; they can be investigated with tools unique to UCI and offer the opportunity for highly collaborative interactions among the participants.
Prostate Cancer Prevention:
Appropriate participants will be directed toward therapeutic prevention trials, either through the Southern California Chemoprevention Consortium (early stage) or Cooperative Group trials.
Prostate Cancer Screening and Diagnostics:
In 2011, more than 240,000 men are projected to be diagnosed with prostate cancer and 33,000 are projected to die from this condition.(1) More than 2.5 million men in the United States are long-term survivors of prostate cancer. Men with a strong family history of prostate cancer and African American men are at increased risk for developing prostate cancer. Most prostate cancer is localized at diagnosis and detected as a result of screening with prostatic-specific antigen (PSA) testing.
Prostate Cancer Therapeutics: Prostate cancers are slow growing and unlikely to spread and most men will receive immediate treatment with surgery or radiation therapy. These therapeutic strategies are associated with short- and long-term complications, including impotence, urinary incontinence or infection. In addition, a small number of men choose observational strategies, which may delay the initiation of curative therapy or avoid it completely. Given the high prevalence of low-risk prostate cancer, there is an urgent need to clarify the role of active surveillance and other observational strategies as alternatives to a more invasive treatment.
GLOBAL BENCHMARKS OF SUCCESS OF THE GU-DOT
1. To increase accrual to clinical trials in prostate cancer.
2. To harness the expertise of investigators from the School of Medicine and School of Biological Sciences to foster collaboration in a multi-disciplinary consortium through which the most important research questions in prostate cancers can be addressed.
3. To develop surgical strategies to further reduce the low rate of complications and relapse obtained by the best surgeons and to disseminate these skills to other centers. An example is the cryogenic methods pioneers at UC Irvine.
4. The major therapeutics is based on variations of androgen ablation therapy, which is quite quickly evaded by many aggressive cancers. There is a need for drug therapies that are synergistic with the current therapies.
This will lead to additional Specific Benchmarks beyond the two listed below (see below).
SPECIFIC BENCHMARKS OF SUCCESS
1. To establish a new PSA Taskforce
2. In the majority of cases, prostate cancer is not the proximal cause of death, if left untreated. There is an urgent need to triage patients into those a) that will benefit from surgery or radiation therapy while b) intervening aggressively with patients that may already have metastases and c) having low risk patients undergo active surveillance
3. Genomics has revealed many potential new somatic risk factors. There is a need for studies to determine how to usefully exploit this information. Genomics has also revealed mutations that recur repeatedly in particular genes in prostate cancers. There is a need for studies for which mutations are relevant and then develop interventions based on these relevant genetic differences.
Dr. Thomas Ahlering GU-DOT co-leader
Vice Chairman, Department of Urology
UC Irvine School of Medicine
Oncology & Robotic Surgery
UC Irvine Healthcare
Dr. Ahlering is a highly regarded surgeon in Urologic cancers. His years
of experience in treatment of prostate, bladder, kidney and testicular cancers
has placed him as one of the original America's Best Doctors since his membership
in 1994. He trained under Dr. Donald G. Skinner at USC in urinary diversion and
reconstruction, and has continued to pioneer innovation to the Indiana pouch,
and Ileal Neo-bladder reconstructions.
Dr. Michael McClelland, Ph.D. GU-DOT co-leader
Professor, Department of Pathology, School of Medicine
Dr. McClelland’s focus
study dys-regulation of genes that occurs in cancer. His lab was the first to
describe that the regulatory regions of mammalian genes, called promoters,
contain sequences called CpG islands. Methylation of these features is
important in marking genes for regulation. He constructed the first “promoter
microarrays” of DNA fragments from 10,000 promoters and collaborated on the
first Chromatin immunoprecipitation-array (ChIP-chip) experiments, which identify
proteins bound to promoters in living cells. The McClelland lab is currently
particularly interested in alterations of gene expression in adjacent normal
tissue during cancer progression.