UC Irvine’s Chao Family Comprehensive Cancer Center (CFCCC) is one of only 45 NCI-Designated Comprehensive Cancer Centers in the United States and the only one in Orange County. The Cancer Center’s robust translational research core in biomarker validation and oncologic imaging, the multi-disciplinary robotics surgery platform, and the intra-operative hyperthermic perfusion chemotherapy program are unique to UC Irvine. More importantly, for patients living in Orange County and surrounding districts, access to the nation’s highest profile phase I-III clinical trials is only available at the Cancer Center.
The Women's Cancer Cure ConneXion Disease Oriented Team (Gyn-DOT) is a multi-disciplinary consortium comprised of UC Irvine investigators from the disciplines of oncology, radiology, pathology, molecular biology/genetics, optics, behavioral sciences, public health, and epidemiology & biostatistics. The Gyn-DOT will engage investigators who have an interest in translational science, comparative effectiveness research in surgery, health care disparities, and drug discovery in breast, ovarian, endometrial, cervical, and vulvar cancers. Additionally, the Gyn-DOT will encompass the Schools of Medicine, Biological Sciences, Physical Sciences, and Engineering. The Gyn-DOT will carry out clinical and translational research under the auspices of the CFCCC.
The cancer surveillance pillar of the Gyn-DOT will be a dynamic (i.e., non-static) Orange County registry which will serve as a repository of all breast and gynecologic cancers and maintained by UC Irvine’s Department of Epidemiology. An important objective of cancer surveillance will be to define the women’s health care racial disparities that may exist in Orange County. Public health needs as they pertain to the county-funded Breast and Cervical Cancer Early Detection Program will also be assessed.
The opening of Ann’s Clinic to screen high risk individuals (BRCA1/2 mutation carriers, MLH2/MSH1 mutation carriers, and/or women with strong family histories of breast/ovarian/uterine/colorectal cancer) in 2012 will allow for genetic counseling, 3D/4D ultrasonography, access to chemoprevention protocols, and risk stratification for suitability for prophylactic surgery. It is anticipated that Ann’s Clinic will identify individuals that may be triaged to the Athena Network for Early Detection of Breast Cancer for which UC Irvine is responsible for enrolling 30,000 subjects. Appropriate participants will be directed toward therapeutic prevention trials, either through the Southern California Chemoprevention Consortium (early stage) or Cooperative Group trials.
Critical to the diagnostics program of the Gyn-DOT will be to establish and maintain the annotated biorepository. Tissues retrieved at the time of surgery at UC Irvine Medical Center will provide source material for the biorepository. Microarrays will be prepared at the Queen of Hearts Laboratory in Spraque Hall and used for biomarker discovery (training and validation sets). The first translational research of the WCCC will be the conduct of Dr. Krishnansu Tewari’s NIH R21 to study surrogate markers of angiogenesis and BRCA1/ERCC1 excision repair in cervical cancer tissues. A second integral component of the diagnostics paradigm of the Gyn-DOT will be the further development of onco-imaging through collaboration with investigators from the department of nuclear medicine, Beckman laser institute, and Schools of Engineering and Physical Sciences.
The therapeutics program will focus on IIT phase I/II trials, the cooperative group mechanism (e.g., GOG-NSABP-RTOG), and industry-supported phase II trials (randomized, non-randomized, and phase III run-ins) as they pertain to drug discovery. Industry support to study surgical technology (e.g., robotics, photodynamic, intra-operative hyperthermic perfusion chemotherapy (HIPEC), etc.) will also be pursued.
Comparative effectiveness research and the formal study of health care disparities as they exist in breast and gynecological cancers will primarily occur within the survivorship/quality of life branch of the Gyn-DOT.
GLOBAL BENCHMARKS OF SUCCESS OF THE Gyn-DOT:
• To increase accrual to clinical trials in breast and gynecologic cancers.
• 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 breast and gynecologic cancers can be addressed. This will lead to additional Specific Benchmarks beyond the two listed below.
SPECIFIC BENCHMARKS OF SUCCESS:
1. Accrual to clinical trials (For information on clinical trials here at the Cancer Center, please follow this link)
2. Ovary/Breast cancers — To study technetium labeled EC20 (a folic receptor targeted imaging agent from Endocyte) first in ovarian cancer and then in breast cancer (Su PI). Much of ovarian and breast cancer drug discovery develops in parallel (BRCA testing, anti-angiogenesis therapy, PARP inhibition, etc), and a natural progression for study of EC20 will be transition from ovary (phase III randomized trial pending activation, Tewari PI) to IIT in breast cancer (Su PI). This novel collaboration between targeted therapy efficacy/tolerability and onco-imaging also bridges the molecular cascades that link ovarian and breast cancer. Tewari (Clinical PI), Su (Basic Scientist).
3. Endometrial cancer — David Fruman from Molecular Biology & Biochemistry (Associate Director, Institute of Immunology) is developing an mTOR/PI3K inhibitor together with Intellikine, Inc. At present, Genentech’s mTOR/PI3K inhbitor trial in endometrial cancer is approaching activation at UC Irvine (Tewari PI). Dr. Fruman’s expertise in mTOR/PI3K inhibition will allow for the acquisition of tissue samples from both the Genentech and Intellikine trials to perform translational studies that would serve the objectives of the exploratory endpoints of each individual phase II trial. This should provide sufficient preliminary data for an R21 application. Tewari (Clinical PI), Fruman (Basic Scientist).
Associate Professor, Department of Obstetrics & Gynecology, School of Medicine
Director of Research- Gynecologic Oncology. Dr. Tewari heads a UC Irvine led consortium of 13 medical centers — including those at UC San Diego, UC San Francisco and Stanford University — that combine resources to support gynecologic oncology trials. He is currently conducting a nationwide Phase III trial to see how Avastin can improve cervical cancer outcomes. "I can’t think of another gynecologic oncology group that has accomplished as much as UC Irvine," Tewari says. "We have the infrastructure and expertise in clinical trials. The foundations of our division include these trials, drug discovery, translational science and robotic surgery. All those elements are found in abundance at UC Irvine." Dr. Tewari has NIH funding to study surrogate markers of angiogenesis in cervical cancer as well as funding to study robotic surgery in cervical cancer. He is listed in the prestigious Best Doctors of America and for many years has been listed as one of the Top Doctors in Orange County in Gynecologic Oncology by the Orange County Medical Association.
Dr. Lydia Su, co-leader