Gynecologic Cancer Research Program at the Chao Family nci-designated Comprehensive Cancer Center at uc irvine
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DISEASE ORIENTED TEAMS (DOTs) The Chao Family Comprehensive Cancer Center Research Programs have been restructured to reflect the following: Research Programs
Areas of emphasis include cancer relevant molecules at the level of atoms and bonds using biophysical and chemical techniques including the development of novel tools.
Areas of emphasis include advanced imaging and cellular technology integrated for clinical benefits.
Areas of emphasis include Dynamic interactions between cancer cells and their environment (systems and organs) with respect to specific types of cancer (organs) and the signaling pathways relevant to these cancers (pathways). The overarching goal is to identify key proteins or points of crosstalk for therapeutic intervention (targets).
Similarly, the function and purpose of the Translational Working Groups (TWGs) have been reviewed. The TWGs have been reorganized and have evolved into Disease Oriented Teams (DOTs) to reach across the new Research Programs with a broader mandate than the previous TWGs. The DOTs have the support of the CFCCC Director, School of Medicine Dean’s Office, and the CEO of the UC Irvine Medical Center. Teams have been established to complement our Programs, Health Affairs strategic plans, and patient population:
DOT Mandate/Impact
WOMEN’S CANCER CURE CONNEXION DOT LEADERS: KRISHNANSU S. TEWARI, M.D. LYDIA SU, Ph.D. 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 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. PROPOSAL: The Women's Cancer Cure ConneXion Disease Oriented Team (WCCC-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 WCCC-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 WCCC-DOT will encompass the Schools of Medicine, Biological Sciences, Physical Sciences, and Engineering. The WCCC-DOT will carry out clinical and translational research under the auspices of the CFCCC. The WCCC-DOT will have the following programmatic components:
The cancer surveillance pillar of the WCCC-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 WCCC-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. 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 WCCC-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 HDII 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 WCCC-DOT. GLOBAL BENCHMARKS OF SUCCESS OF THE WCCC-DOT:
SPECIFIC BENCHMARKS OF SUCCESS:
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 HDII 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 UCI (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). Women’s Cancer Cure ConneXion DOT LEADERSHIP: DR. KRISHNANSU TEWARI CO-LEADER 
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 UCI.” 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 Professor, Department of Radiological Sciences, School of Medicine Director of Tu & Yuen Center for Functional Onco-Imaging Dr. Su is conducting clinical trials using targeted PET imaging tracers to monitor early molecular changes after chemotherapy. In addition to cancer imaging, she is also interested in investigating the role of breast density analyzed on MRI, including volume and morphological distribution pattern, for cancer risk prediction and chemoprevention. 2012 WCCC-DOT TEAM: DR. HODA ANTON-CULVER - EPIDEMIOLOGY 
Professor & Chair, Department of Epidemiology, School of Medicine Director, Genetic Epidemiology Research Institute Dr. Anton-Culver's research is in the broad scientific areas of cancer epidemiology and cancer genetics. Her research focuses on cancer epidemiology with special emphasis on etiology, molecular genetic characterization, evaluation of genetic-phenotype correlation, and genotype-environment interaction using large populations of cancer patients, their relatives, and unaffected controls. Dr Anton-Culver’s research theme takes advantage of population genetics, to predict the proportion of cancers that can be attributed to genetic variation and exposure to environmental risk factors in the population. DR. HANS ULRICH BERNARD - CANCER GENETICS 
Professor, Department of Molecular Biology & Biochemistry, School of Biological Sciences. Dr. Bernard’s research interests include the following: Regulation of gene expression of papillomaviruses and its relevance for progression of cancer of the cervix; phylogenetic and genomic variability of papillomavirus genomes and its impact on the etiology and epidemiology of cancer of the cervix; and cholinergic signaling during cervical carcinogenesis. DR. ROBERT BRISTOW - GYNECOLOGIC ONCOLOGY 
Professor, Department of Obstetrics & Gynecology, School of Medicine Dr. Bristow has pioneered advanced techniques for the management of a variety of gynecological cancers. Recognized internationally as a leading expert in ovarian, fallopian tube, primary peritoneal and endometrial cancers, he is the author of five books on ovarian cancer and he has published extensively in the field of ovarian cancer research. Recently, he was appointed to the UC Irvine School of Medicine’s Philip J. DiSaia Chair in Gynecologic Oncology, becoming the first to hold the endowed chair named for the University's highly respected former Chief of the Division of Gynecologic Oncology. Dr. Bristow's research interests and expertise center around health services outcomes and access to care for women with gynecologic cancer. DR. JOHN BUTLER – SURGICAL ONCOLOGY 
Professor, Department of Surgery, School of Medicine Dr. Butler’s research interests include oncologic surgery, breast cancer, endocrine surgery, sarcoma. His research abstract is Novel Imaging Techniques in the Early Diagnosis of Breast Cancer- Laser Technology in the Diagnosis and Management of Breast Cancer, Skin Sparing Mastectomy- Minimally Invasive Endocrine Surgery: Thyroid, Parthyroid, Adrenal Multidisciplinary Treatment of Soft Tissue Sarcoma. Dr. Butler is the chief of oncologic surgery oncology at the Chao Comprehensive Cancer Center. He has made a number of advances with the use of minimally invasive surgical techniques to aid the treatment and recovery of patients with breast cancer. DR. PARIMA DAROUI - RADIATION ONCOLOGY 
Assistant Professor, Department of Radiation Oncology, School of Medicine Dr. Daroui is a physician-scientist with clinical interests in the treatment of breast cancer and central nervous system malignancies. Her research interests encompass both clinical and translational research, with an emphasis on improving cancer care. Dr. Daroui’s research projects have included topics such as pattern of care and quality improvement initiatives for breast cancer and accelerated partial breast irradiation. She has published in multiple peer-reviewed journals and has presented at numerous national and international scientific meetings. She previously served as a member of the RSNA Task force on Oncological Imaging and Therapies and currently serves as a committee member of the ASTRO Radiation and Cancer Biology Research Council. DR. RAMEZ N. ESKANDER – GYNECOLOGIC ONCOLOGY Fellow, Clinical Instructor, Department of Obstetrics & Gynecology, School of Medicine Dr. Ramez Eskander's interests focus on quality of life and therapeutic paradigms in patients with ovarian cancer. His current projects focus on beta-blocker use in ovarian cancer patients, impact of delayed initiation of chemotherapy on survival and the the potential affect of chemotherapy-induced-neutropenia on oncologic outcomes. He is also investigating the impact of the PARO robot on ovarian cancer patient quality of life during chemotherapy. Dr. Eskander is currently a Fellow in the Gynecologic Oncology Training Program at UC Irvine Medical Center. He serves as a clinical instructor of Obstetrics and Gynecology and has devoted many years to research in the medical field. His works have resulted in several national presentations, and 11 peer reviewed publications. 
DR. JOHN FRUEHAUF – CANCER GENETICS 
Associate Professor of Clinical Medicine, Department of Biomedical Engineering, and Biological Chemistry, The Henry Samueli School Engineering. Dr. Fruehauf’s research interests include understanding the mechanisms of drug action and resistance with the goal of improving therapeutic outcomes for cancer patients. Dr. Fruehauf’s group has focused on mechanisms of drug action and resistance with the goal of developing predictive tests that improve therapeutic outcomes for cancer patients. Active areas in his laboratory at UC Irvine include the role of glutathione and redox mechanisms in drug resistance, development of vascular endothelial cell models to predict response to antiangiogenesis agents, and the examination of differential gene expression that can distinguish between drug resistant and drug sensitive tumors. Recently Dr. Fruehauf’s team is focused on translating their bench work to the bedside through the development of clinical trials that include correlative laboratory studies. DR. DAVID FRUMAN – CANCER GENETICS 
Associate Professor, Department of Molecular Biology & Biochemistry, School of Biological Sciences. Dr. Fruman is the Associate Director of the UC Irvine Institute for Immunology, and Director of the Ph.D. program in Cellular and Molecular Biosciences (CMB). Within the CMB program, Dr. Fruman is affiliated with the Immunology and Cancer Biology research areas. His research interests are focused on signal transduction. Mammalian cells express many isoforms of phosphoinositide 3-kinase (PI3K), and many putative effector proteins have been identified. One of these effectors is a protein kinase called the target of rapamycin (TOR). Dr. Fruman's laboratory is interested in the role of PI3K and TOR in the function of normal cells and in the development of cancer cells. Studies in his lab center on cells of the immune system, both normal lymphocytes and their transformed counterparts.
DR. JEFFREY V. KUO- RADIATION ONCOLOGY 
Associate Clinical Professor, Department of Radiation Oncology, School of Medicine Dr. Kuo’s research focus includes the following: Brachy Therapy, Gynecologic Oncology, Conformal Radiation Therapy, HIV Related Oncology, Medical Humanities. He is interested in the treatment of challenging nonstandard problems in oncology as a paradigm for optimizing general oncologic treatment strategies. Typically his clinical research encompasses a variety of leading edge technologies and strategies, such as altered fractionation, radioactive implants (brachytherapy), re-irradiation strategies, 3-D conformal therapy, intensity modulated radiation therapy, and chemoradiotherapy.
Dr. Lee’s research interests include cell cycle checkpoint pathways and molecular genetics studies of breast cancer using mouse model systems. Eva Lee and her laboratory continue to conduct investigations on tissue-specific functions of breast and ovarian cancer susceptibility genes, BRCA1 and BRCA2, and interactions between tumor suppressors and endocrines. Dr. Lee's group demonstrated that inhibition of the stabilized progesterone receptor in BRCA1 and p53-mutated mammary epithelial cells prevented or delayed mammary tumors. Her team has continued to focus on the mechanisms of progesterone receptor stabilization as well as the usage of anti-progesterone in breast cancer prevention and progesterone receptor positive breast cancer treatment. How mutations of BRCA genes affect mammary epithelial cell fates and mechanisms of cancer stem cells expansion during the course of chemo-resistance are being studied. DR. Rita S. Mehta-Medical Oncology 
Associate Clinical Professor, Department of Medicine, School of Medicine Dr. Mehta’s research interests include Cancer Angiogenesis, Targeted/Individualized Therapeutic Options, Clinical and Translational Research. An example of her research abstract is the following: Cancer Angiogenesis – She studied the p53 gene and its involvement in angiogenesis cascade. Data suggest that the level of expression of the p53 gene may be related to modulation of thrombospondin-1, an angiogenesis inhibitor, and that an angiogenesis index incorporating p53, thrombospondin-1 and angiogenesis has prognostic implications in breast, prostate, colorectal cancer. In this way an angiogenic capacity in cancer patients may be identified prior to treatment with a potential effective/ineffective antiangiogenic agent in an individual patient or in an individual cancer type. Recent approval of avastin is the substantiation of an important role of antiangiogeneic compounds in treatment of cancer. 
DR. KATHRYN OSANN - BIOSTATISTICS, EPIDEMIOLOGY Adjunct Professor, Department of Medicine, School of Medicine Dr. Osann has been the principal investigator on several epidemiologic studies and has extensive experience as a consulting statistician and co-investigator on a variety of medical research projects at UC Irvine. Her expertise includes study design, data collection, database setup, statistical analysis, and interpretation and summary of results. She is a member of the Chao Family Comprehensive Cancer Center and participates as a statistical reviewer in the Cancer Center’s Clinical Trials Protocol Review and Monitoring Committee. Dr. Osann also participates in the biostatistics shared resource for the newly funded Institute for Clinical and Translational Science. Osann’s research interests include epidemiology, tobacco-related diseases, cancer, cancer prevention, skin cancer, lung cancer, tobacco use prevention, and gender differences. DR. LESLIE RANDALL – GYNECOLOGIC ONCOLOGY 
Assistant Professor, Department of Obstetrics and Gynecology, School of Medicine Dr. Randall completed her fellowship in Gynecologic Oncology in 2009 under a T32 Training Grant awarded to UC Irvine. Here she was trained in both translational and clinical research methods, completing 3 translational manuscripts for the cooperative Gynecologic Oncology and Southwest Oncology Groups. Her current research interests include clinical investigation of novel therapeutics and pre-clinical investigation of functional radiologic imaging (MRI with single-photon emission computed tomography) markers of tumor response to these therapies. Dr. Randall offers a full range of services to women with and at risk for gynecologic cancers including minimally-invasive and radical surgery, fertility-sparing surgery, and complicated chemotherapy regimens. 
DR. LISA SPARKS- PUBLIC HEALTH, BIOBEHAVIORAL Adjunct Professor, Department of Health Sciences and Public Health and Presidential Research Fellow of Health and Risk Communication at Chapman University in Orange, California where she serves as Director of Graduate Studies for the Master of Science in Health Communication in the Schmid College of Science and Technology. In addition, Dr. Sparks also serves as a full member of the Chao Family/NCI Designated Comprehensive Cancer Center at the University of California, Irvine in the School of Medicine (SOM) in the Division of Population Sciences, and has a faculty appointment in the Program in Public Health (PHP), College of Health Sciences (COHS). DR. LARI WENZEL – PUBLIC HEALTH, BIOBEHAVIORAL 
Professor, Department of Medicine, School of Medicine Dr. Wenzel is focused on the Health-Related Quality of Life Outcomes, Patient-Reported Outcomes in Gynecologic Cancer Clinical Trials, Cancer Survivorship; Chair, Health Outcomes Committee Gynecologic Oncology Group; Director, Biobehavioral Shared Resource at the Chao Comprehensive Cancer Center, College of Medicine, University of California, Irvine. Together with Dr. Nelson, who is the principle investigator on several clinical trials including, 1) studies of the growth factor GM-CSF, which is a requisite trophic factor for dendritic cells, as an immunomodulatory biological adjuvant, and 2) studies conducted with Dr. Wenzel to explore the impact of individual psychosocial interventions, designed to improve cancer survivor’s quality of life, on their neuroendocrine and immune systems, the so-called “mind-body connection”. The Nelson/Wenzel team has provocative data supporting cancer survivorship as a chronic stressor and a positive impact on the immune system when this stress is diminished. They are conducting a large NIH funded confirmatory clinical study. APPENDIX 1 Table 1 – Research Priorities in Breast and Gynecologic Cancers
APPENDIX 2: Qualifications for Dr. Tewari as the WCCC-DOT Leader: A. Current Position at UC Irvine 1. Associate Professor in Obstetrics & Gynecology 2. Director of Research in Gynecologic Oncology 3. Diplomat of the American Board of Obstetrics & Gynecology and Gynecologic Oncology B. Experience in Clinical Trial Design and Execution:
C. Experience in Translational Research
D. Clinical Practice Performance
APPENDIX 3: Qualifications for Dr. Su as the WCCC-DOT Co-Leader: Dr. Lydia Su has had more than 17 years of experience working on cancer imaging using dynamic contrast enhancement (DCE-MRI). She oversees the clinical breast MRI research program at UCI since 1999. Recently, her effort is on development of quantitative image analysis algorithms for segmentation and morphology/texture characterization; utilizing these imaging biomarkers to build computer-aided diagnosis systems for differentiating between patients with benign and malignant breast lesions, and good NAC responders vs. poor responders. During the preceding three years, her group has been working on developing a quantitative analysis method to measure breast density and the breast parenchyma morphology. Additionally, Dr. Su is providing an improved risk prediction model for estimating each individual woman’s cancer risk, and also providing a surrogate marker for predicting the efficacy of hormonal therapy. Dr. Su’s team is one of the most active research groups in breast MRI research, and the findings were frequently quoted in international conference meetings. In addition to breast MRI, she is leading the effort in development of prostate MRI, which is one highlighted research areas of the cancer center. Other than MRI, Dr. Su has been working on molecular imaging of cancer using PET and scintigraphic imaging techniques. Current Positions 2008– Professor, Departments of Radiological Sciences and Physics, UC Irvine, CA 2011– Director of Tu & Yuen Center for Functional Onco-Imaging, UC, Irvine, CA
NIH/NCI R01 CA127927 (Su M-Y) 04/01/2008 – 1/31/2013 Prediction of Neoadjuvant Chemo Pathological Response Using MRI Markers Siemens Molecular Imaging (Su M-Y) 5/2011 – An Exploratory, Open Label, Non-randomized, Multi Center Study of [F-18]CP-18 Siemens Molecular Imaging (Su M-Y) 5/2010 – A Phase II, Open Label, Non-Randomized, Multi-Center, Pilot, Efficacy Study of [F-18]RGD-K5 Positron Emission Tomography (PET) As A Tool To Monitor Response To An Anti-Angiogenic Drug CBCRP 16GB-0056 (Su M-Y) 7/1/2010 – 6/30/2012 MRI Registration for Therapy Evaluation and Annual Screening NIH/NCI R03 CA136071-01A1 (Chen, J-H) 3/1/2009 – 2/28/2012 Evaluation of 3D MRI-Based Quantitative Breast Density for Chemoprevention NIH/NCI R21/33 CA120175 (Gulsen G.) 08/1/07 – 07/31/12 Development of a Multi-Modality System for Onco-Imaging Yüklə 95,88 Kb. Dostları ilə paylaş:
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