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DCTD 2010 Program Accomplishments Division of Cancer Treatment and Diagnosis National Cancer Institute 2010 Program Accomplishments 2010 U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health NATIONAL CANCER INSTITUTE DIVISION OF Cancer Treatment and Diagnosis Program Accomplishments 2010 U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health TABLE OF CONTENTS PREFACE 4 DIVISION OF CANCER TREATMENT AND DIAGNOSIS 6 Overview 7 Major Initiatives and Accomplishments 10 CANCER DIAGNOSIS PROGRAM 26 Overview 27 Structure and Function 30 Program Accomplishments 33 Future Initiatives 47 Selected Publications 48 CANCER IMAGING PROGRAM 54 Overview 55 Structure and Function 58 Program Accomplishments 61 Selected Publications 80 CANCER THERAPY EVALUATION PROGRAM 86 Overview 87 Program Accomplishments 93 Future Directions 118 Selected Publications 119 DEVELOPMENTAL THERAPEUTICS PROGRAM 124 Overview 125 Structure and Function 130 Program Accomplishments 131 Selected Publications 156 2 DCTD PROGRAM ACCOMPLISHMENTS 2010 RADIATION RESEARCH PROGRAM 160 Overview 161 Structure and Function 163 Program Accomplishments 167 Future Initiatives 169 Selected Publications 172 TRANSLATIONAL RESEARCH PROGRAM 178 Overview 179 Background 183 Program Accomplishments 186 Program Collaborations 197 Future Initiatives 201 Selected Publications 201 BIOMETRIC RESEARCH BRANCH 204 Overview 205 Background 205 Program Accomplishments 208 Future Initiatives 218 Selected Publications 219 OFFICE OF CANCER COMPLEMENTARY AND ALTERNATIVE MEDICINE 226 Overview 227 Background 227 Collaborations 232 Future Initiatives 235 Selected Publications 235 APPENDIX 238 Division of Cancer Treatment and Diagnosis Staff Roster 239 DIVISION OF CANCER TREATMENT AND DIAGNOSIS 3 PREFACE This edition of Program Accomplishments of the Division of Cancer Treatment and Diagnosis (DCTD) offers a multi-year review of the undertakings and achievements of this segment of the National Cancer Institute (NCI). Though not meant to be a complete inventory of the division, this report covers activities and advances from 2005 through 2010 and provides important highlights during my tenure that have helped advance the diagnosis and treatment of cancer. Our greatest challenge is to increase the speed with which new treat- ments are brought to the millions of Americans with cancer. DCTD has implemented a number of actions to streamline the drug discovery and development process. Chief among them is the transformation of the NCI therapeutics pipeline. Working with the NCI Center for Cancer Research (CCR), we now have a unified platform, the NCI Experimental Therapeutics (NExT) program, which allows researchers to enter can- didate agents into the pipeline at any of a number of key steps, such as the discovery stage or preclinical drug development. Researchers may come from academia and CCR as well as biotechnology and pharma- ceutical companies. Other entry points further down the development Dr. James H. Doroshow, Director, pipeline include providing agents for testing in early- and late-stage NCI Division of Cancer Treatment clinical trials. In conjunction with NExT and operated similarly, DCTD and Diagnosis has just implemented the Clinical Assay Development Program (CADP) to generate new assays that could significantly advance the ability to choose among cancer treatments for an individual patient. In the past, clinical trial commencement was often a long and arduous process, some- times taking years. Upon recommendations from the Operational Efficiency Working Group, we have overhauled the process of initiating clinical trials so that, as of January 1, 2011, the time allowed from submission of a concept to activation has been cut in half. For phase 1 and 2 trials, the process is targeted to take 210 days from the time that a concept is submitted to the NCI Cancer Therapy Evaluation Program (CTEP) to the time that a trial is begun. Phase 1 and 2 trials will be terminated if they are not activated in 18 months. For phase 3 studies, the target for submission to opening is 300 days, with a drop-dead date for activation of 24 months. NCI has also made administrative changes within the institute to increase the efficiency with which clinical trials are conducted. In addition, upon the 2007 recommendations of the Translational Research Working Group, a Translational Research Program was created within DCTD to move promising basic research discoveries into phase 1 clinical studies. Together, these changes should make better use of resources and increase each trial’s chance of completion. 4 DCTD PROGRAM ACCOMPLISHMENTS 2010 To eliminate possible redundancies and to ensure that only the most promising agents and scientifically sound proposals are approved, NCI has successfully retooled the way clinical trials are selected. Following the advice of the 2005 Clinical Trials Working Group Report, nine disease-specific steering committees for phase 3 and large phase 2 studies and one investigational drug steering committee for phase 1 and 2 trials have been established to develop, prioritize, and evaluate clinical trial proposals. This report also underscores the contributions of the 2009 American Recovery and Reinvestment Act (ARRA), which has provided the necessary support for the division to continue critical programs that otherwise would have been extremely difficult to fund and to more rapidly advance initiatives that were already under way. These efforts span the spectrum of therapeutics development, including validation of potential targets, identification and movement of hit-to-lead molecules, conduct of preclinical activities required for an investigational new drug filing, production and formulation of critical therapeutics, and support for several key phase 0, 1, and 2 clinical trials. Recent advances in cancer treatment and diagnosis are also highlighted in this report. Among them are a practice-changing treatment for neuroblastoma with a monoclonal antibody; the results of a landmark 8-year clinical trial of current and former smokers, conducted in partnership with our colleagues in the NCI Division of Cancer Prevention, clearly showing that screening with helical computed tomography reduces lung cancer mortality; and successful preclinical research that has led to the approval for 70% of the anticancer treatments marketed today, including the new prostate cancer therapeutic sipuleucel-T (Provenge®), the first-ever vaccine for cancer treatment. In these pages, the reader will find summaries of recently established priorities and scientific advances made possible by the many talented and committed staff members throughout the division. DIVISION OF CANCER TREATMENT AND DIAGNOSIS 5 2010 Program Division of Cancer Accomplishments Treatment and Diagnosis 6 DCTD PROGRAM ACCOMPLISHMENTS 2010 OVERVIEW The Developmental Therapeutics Program (DTP) serves as a vital resource in discovering The Division of Cancer Treatment and potential cancer therapeutics and acquiring Diagnosis (DCTD) takes prospective information pertaining to their preclinical detection and treatment leads, facilitates development. The program provides their paths to clinical application, and research materials and manufactures new expedites the initial and subsequent agents in bulk quantities for use in investi- large-scale testing of new agents, gational new drug (IND)-directed studies. biomarkers, imaging tests, and other diagnostic and therapeutic interventions The Radiation Research Program (RRP) (radiation, surgery, immunotherapy) provides expertise to investigators who in patients. perform novel radiotherapy research and assists in establishing future directions for DCTD has eight major programs that work radiation research. together to bring unique molecules, diagnostic tests, and therapeutic interventions from the The Translational Research Program (TRP) laboratory bench to the patient bedside: translates novel scientific discoveries from laboratory and/or population studies to The Cancer Diagnosis Program (CDP) stimulates, the clinic for testing in cancer patients coordinates, and funds specimen resources, and determines the biological basis for databases related to those specimens, and clinical observations. research on diagnostics and improved technologies to better characterize tumors. The Biometric Research Branch (BRB) provides state-of-the-art statistical and biomath- The Cancer Imaging Program (CIP) uses new ematical analyses for DCTD and other NCI technologies to expand the role of imaging components. in noninvasive diagnosis, identification of disease subsets in patients, disease staging, The Office of Cancer Complementary and and treatment monitoring. Alternative Medicine (OCCAM) aims to increase the amount of high-quality cancer research The Cancer Therapy Evaluation Program (CTEP) and information about the use of comple- functions as the National Cancer Institute’s mentary and alternative modalities. (NCI’s) primary clinical evaluator of new anticancer agents, radiation treatments, and Additional information about NCI’s Division surgical methods. The program administers of Cancer Treatment and Diagnosis is the 11 cooperative research groups that available at http://dctd.cancer.gov and unite researchers around the nation and http://cancer.gov. the world in the pursuit of distinctive and effective new treatments for cancer. DIVISION OF CANCER TREATMENT AND DIAGNOSIS 7 JAMES H. DOROSHOW, DIRECTOR James H. Doroshow, M.D., FACP, has been the Director of the Division of Cancer Treatment and Diagnosis (DCTD), National
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