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Women's Cancer Cure ConneXion Disease Oriented Team (WCCC- DOT)

DISEASE ORIENTED TEAMS (DOTs)

The Chao Family Comprehensive Cancer Center Research Programs have been restructured to reflect the following:

Research Programs

  • Chemical and Structural Biology(CSB) Leadership: Thomas Poulos, Greg Weiss

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.

  • Onco-Imaging and Biotechnology(OIB) Leadership: Chris Hughes, Bruce Tromberg, Lydia Su (theme).

Areas of emphasis include advanced imaging and cellular technology integrated for clinical benefits.

  • Systems Pathways and Targets(SPT) Leadership: John Lowengrub, Marian Waterman

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).

  • Cancer Prevention and Prognosis(CPP) Leadership: Christine McLaren,Daniel Mercola, and Michael McClelland (theme). Areas of emphasis include the understanding of molecular and genetic events in selected areas of cancer etiology through prognosis that can be translated for clinical benefit.

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:

  • Women’s Cancer – Leadership: Krishnansu Tewari M.D., Lydia Su, Ph.D. Dr. Tewari is director of Research in Gynecologic Oncology, and Dr. Su is director of Oncology Imaging with a long term commitment to Breast Cancer. Anticipated release date is April 1, 2012.
  • Colon Cancer–Leadership: Jason Zell, D.O. MPH, Robert Edwards M.D.Ph.D., and Michael J. Stamos, M.D. Dr. Zell is a hematologist/oncologist, Dr. Edwards is a pathologist who specializes in human colonic stem cells, and Dr. Stamos is a colorectal surgeon.
  • Prostate Cancer– Leadership: Thomas Ahlering, M.D., John Krolewski, M.D. and Anne Simoneau M.D. Drs. Ahlering & Simoneau are urologists who specialize in prostate cancer, and Dr. Krolewski is a pathologist and Principal Investigator of prostate focused research project grants. Anticipated released date is September 1, 2012.
  • Skin Cancer– Leadership: Anthony J. Durkin, Ph.D. and Kristen Kelly M.D. Dr. Durkin specializes inthe development and translation of optical technologies to biomedical problems with an emphasis on skin disease, and Dr. Kelly is a dermatologist with expertise in translation of optical technologies as well as clinical experience in diagnosis and treatment of non-melanoma (squamous cell) and melanoma cancer. Anticipated release date is May 1, 2012.

DOT Mandate/Impact

  • To identify recruitment needs
  • To promote the clinical trials portfolio and motivate accrual
  • Lead broad-based (across Research Programs)disease team meetings focusing upon clinical research
  • To provide guidance for prioritization of clinical research needs
  • Mentor CFCCC scientists into clinical research
  • Incorporate Early Detection Research Network and Biorespository Banks intoclinical activities
  • Support and facilitate increase in new analyticalpatients to UC Irvine Medical Center and increased patient services to existing patients by the following:
  • Leveraging existing Health Affairs efforts to grow Primary Care unit(s)
  • Collaborate with Business Development, Marketing, Center for Personalized Medicine, and Oncology Divisions and all applicable departments to promote UC Irvine Medical Center and the unique opportunities and services available to patients.

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 CancerCenter’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 OrangeCounty and surrounding districts, access to the nation’s highest profile phase I-III clinical trials is only available at the CancerCenter.

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:

  1. Cancer surveillance
  2. Screening & prevention
  3. Diagnostics
  4. Therapeutics
  5. Survivorship & quality of life

The cancer surveillance pillar of the WCCC-DOT will be a dynamic (i.e., non-static) OrangeCounty 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’shealth care racial disparities that may exist in OrangeCounty. 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 theannotated 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:

  • 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
  2. GOG (K.Tewari)
  3. Athena Breast Health Network (L. Su)

2. Ovary/Breastcancers– 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),anda natural progression for study of EC20 will be transition from ovary (phase III randomized trial pending activation, TewariPI) 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 providesufficient 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 UCIrvine 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 UCIrvine,” 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 OrangeCounty 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 earlymolecularchanges after chemotherapy. Inadditionto cancer imaging, she is also interested in investigating the role of breast densityanalyzed on MRI,includingvolume and morphological distribution pattern, for cancer riskpredictionand chemoprevention.

2012 WCCC-DOT TEAM:

DR. HODA ANTON-CULVER - EPIDEMIOLOGY

Professor & Chair, Department of Epidemiology, School of Medicine Director,GeneticEpidemiologyResearchInstitute
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'sresearch 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, AdrenalMultidisciplinary 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 teamisfocused 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.