P Greenwald

National Institutes of Health, 베서스다, Maryland, United States

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Publications (181)1613.44 Total impact

  • Barbara K. Dunn · Peter Greenwald · Darrell E. Anderson
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    ABSTRACT: Introduction Cancer Prevention Strategies in Older Adults Other Issues for Cancer Prevention in Older Adults The Future of Cancer Prevention in Older Adults References
    No preview · Article · Jan 2013
  • Asad Umar · Barbara K Dunn · Peter Greenwald
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    ABSTRACT: Prevention of cancer remains the most promising strategy for reducing both its incidence and the mortality due to this disease. For more than four decades, findings from epidemiology, basic research and clinical trials have informed the development of lifestyle and medical approaches to cancer prevention. These include selective oestrogen receptor modulators and aromatase inhibitors for breast cancer, the 5-α-reductase inhibitors finasteride and dutasteride for prostate cancer, and the development of vaccines for viruses that are associated with specific cancers. Future directions include genetic, proteomic and other molecular approaches for identifying pathways that are associated with cancer initiation and development, as well as refining the search for immunologically modifiable causes of cancer.
    No preview · Article · Nov 2012 · Nature Reviews Cancer
  • Barbara K Dunn · Karin Jegalian · Peter Greenwald
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    ABSTRACT: In order to improve the early detection and diagnosis of cancer, give more accurate prognoses, stratify individuals by risk, predict response to treatment, and help the transition of basic research into clinical application, biomarkers are needed that accurately represent or predict clinical outcomes. To be useful in trials for chemopreventive agent development, biomarkers must be subject to modulation, easy to obtain and quantify, and have biological meaning, ideally representing steps in well-understood carcinogenic pathways. Though difficult to validate fully, wisely chosen biomarkers in early-phase trials can inform the prioritization of large-scale, long-term trials that measure clinical outcomes. When well-designed, smaller trials using biomarkers as surrogate endpoints should promote faster decisions regarding which targeted preventive agents to pursue, promising greater progress in the personalization of medicine. Biomarkers could become useful in distinguishing indolent from aggressive forms of ductal carcinoma in situ as well as localized invasive breast and prostate cancer, lesions that are often overtreated. Chemopreventive strategies that reduce the progression of early forms of premalignancy can benefit patients not only by reducing their risk of cancer and death from cancer but also by reducing their need for invasive interventions. Genomic and proteomic methods offer the possibility of revealing new potential markers, especially for diseases whose biology is complex or not well understood. Panels of markers may be used to accommodate the molecular heterogeneity of cancers. Biomarkers in phase 2 prevention trials of combinations of chemopreventive drugs have been used to demonstrate synergistic action of multiple agents, allowing use of lower doses, with less toxicity, a critical feature of interventions intended for cancer prevention.
    No preview · Article · Jan 2011 · Recent results in cancer research. Fortschritte der Krebsforschung. Progrès dans les recherches sur le cancer
  • Barbara K Dunn · Peter Greenwald

    No preview · Article · Aug 2010 · Seminars in Oncology
  • Barbara K Dunn · Paul D Wagner · Darrell Anderson · Peter Greenwald
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    ABSTRACT: A common belief is that the earlier that cancer is detected, the better the chance exists for reduced mortality and morbidity. The advent of new and emerging molecular, genetic, and imaging technologies has broadened the possible strategies for early detection and prevention, but a beneficial impact on mortality needs to be supported by clinical evidence. Molecular markers are being identified that are enhancing our ability to predict and detect cancer before it develops and at the earliest signs of impending carcinogenic transformation. Of the innumerable molecular markers in development, a standalone early detection marker with acceptable sensitivity and specificity is available for bladder cancer, although for most cancer sites there are promising avenues of research that will likely produce results in the next decade. The perfect molecular marker would be one that is inherently related to the disease, specifically to the processes of malignant tumorigenesis or to the defense mechanisms of the individual. For example, mutations associated with increased cancer risk often produce gene products that interfere with tumor-suppressor pathways (eg, DNA repair or cell-cycle control) or support oncogenic pathways (eg, through genetic instability or silencing the apoptotic pathway). Finding molecular markers associated with these processes, and where in the process they produce their actions, can lead to interventions based on maintaining support for the normal process and interrupting the action of the products of the mutation. The search for molecular markers for cancer prevention and early detection presents a formidable challenge that requires a systematic and scientifically sound validation process. The search encompasses a broad range of scientific disciplines, including biochemistry, genetics, histology, immunology, informatic technologies, and epidemiology; strategies to identify and understand molecular markers are approached with multidisciplinary teams focused on understanding the mechanistic basis of cancer and the processes and pathways that underlie carcinogenesis.
    No preview · Article · Jun 2010 · Seminars in Oncology
  • Barbara K Dunn · Peter Greenwald

    No preview · Article · Jun 2010 · Seminars in Oncology
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    Asad Umar · Peter Greenwald

    Preview · Article · Jul 2009 · Cancer Epidemiology Biomarkers & Prevention
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    ABSTRACT: Evidence clearly shows a chemopreventive effect for aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) on colorectal cancer and probably other cancer types; however, data on the risk-benefit profile for cancer prevention are insufficient and no definitive recommendations can be made. Aspirin has emerged as the most likely NSAID for use in chemoprevention because of its known cardiovascular benefit and available safety and efficacy data. Other traditional NSAIDs, particularly sulindac, and selective COX-2 inhibitors are now given to patients at high risk of colorectal cancer, although these drugs do not provide cardioprotection. More studies of aspirin and cancer prevention are needed to define the lowest effective dose, the age at which to initiate therapy, the optimum treatment duration, and the subpopulations for which the benefits of chemoprevention outweigh the risks of adverse side-effects. Although it might be possible to answer some of these questions with longer follow-up of existing clinical trials, randomised controlled trials with new study designs will be needed. Future projects should investigate the effects of aspirin treatment on multiple organ systems. Cancers of interest are colorectal, breast, prostate, lung, stomach, and oesophageal. The main side-effect of aspirin is peptic ulcers; therefore coadministration of aspirin with a proton-pump inhibitor is an attractive option and is under investigation in the AspECT trial.
    Full-text · Article · Jun 2009 · The Lancet Oncology
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    Peter Greenwald · Barbara K Dunn
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    ABSTRACT: The application of epidemiology to cancer prevention is relatively new, although observations of the potential causes of cancer have been reported for more than 2,000 years. Cancer was generally considered incurable until the late 19th century. Only with a refined understanding of the nature of cancer and strategies for cancer treatment could a systematic approach to cancer prevention emerge. The 20th century saw the elucidation of clues to cancer causation from observed associations with population exposures to tobacco, diet, environmental chemicals, and other exogenous factors. With repeated confirmation of such associations, researchers entertained for the first time the possibility that cancer, like many of the infectious diseases of the time, might be prevented. By the mid-20th century, with antibiotics successfully addressing the majority of infectious diseases and high blood pressure treatment beginning to affect the prevalence of heart disease in a favorable direction, the focus of much of epidemiology shifted to cancer. The early emphasis was on exploring, in greater depth, the environmental, dietary, hormonal, and other exogenous exposures for their potential associations with increased cancer risk. The first major breakthrough in identifying a modifiable cancer risk factor was the documentation of an association between tobacco smoking and lung cancer. During the past four decades, epidemiologic studies have generated population data identifying risk factors for cancers at almost every body site, with many cancers having multiple risk factors. The development of technologies to identify biological molecules has facilitated the incorporation of these molecular manifestations of biological variation into epidemiologic studies, as markers of exposure as well as putative surrogate markers of cancer outcome. This technological trend has, during the past two decades, culminated in emphasis on the identification of genetic variants and their products as correlates of cancer risk, in turn, creating opportunities to incorporate the discipline of molecular/genetic epidemiology into the study of cancer prevention. Epidemiology will undoubtedly continue contributing to cancer prevention by using traditional epidemiologic study designs to address broad candidate areas of interest, with molecular/genetic epidemiology investigations honing in on promising areas to identify specific factors that can be modified with the goal of reducing risk.
    Preview · Article · Apr 2009 · Cancer Research
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    Peter Greenwald · Barbara K Dunn
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    ABSTRACT: Three decades of intensive experimental and clinical research on cancer prevention have yielded an impressive body of scientific knowledge about cancer epidemiology, causation, and preventative measures. Despite our increased understanding in these critical areas, this knowledge is not being translated adequately into initiatives that will impact public health. The recent release of the World Cancer Research Fund/American Institute for Cancer Research report on diet and lifestyle strategies for cancer prevention--grounded in an evidence-based, systematic review of the published literature--is a strong acknowledgment of the benefits of a lifestyle approach to reduce cancer risk. The report also emphasizes the need to increase basic nutritional science research to make optimal use of the knowledge gained in the past three decades. Medical approaches--represented by chemoprevention clinical trials--also have become more focused based on results from basic science leads. The expansion of preclinical chemoprevention studies and greater attention to "first-in-human" prevention trials that safely shorten the timeline for new drug development are needed. The development of a prevention focus for what the U.S. Food and Drug Administration calls "exploratory investigational new drug studies" and what investigators at the National Cancer Institute are calling "phase 0" clinical trials will contribute to the decision-making involved in designing larger cancer prevention clinical trials. Past achievements in phase III prevention clinical trials--such as the Prostate Cancer Prevention Trial, the Breast Cancer Prevention Trial, and the Study of Tamoxifen and Raloxifene--have provided early successes as evidence of the potential for public benefit to be derived from this research. Nevertheless, the application of these findings to clinical practice and the design of future prevention trials remains a challenge. Current strategies include the refinement of risk assessment models for several major cancers. Additional initiatives, based on emerging basic and clinical research, involve the development of potential biomarkers for cancer risk and early detection by the National Cancer Institute's Early Detection Research Network. Although a recent progress report indicates that biomarkers of cancer susceptibility and exposure have been identified, continued work is needed to validate such markers for clinical use. Using this information optimally for prevention through lifestyle changes or medical interventions will demand commitments from public and private research institutions. Another area of emerging research is the development of a systems biology approach to cancer prevention. This will demand the creation of multidisciplinary teams of researchers from biological sciences, informatics and engineering scientists, and researchers from many fields not generally focused on disease prevention. To facilitate this and other new approaches, and to make effective use of information and strategies for cancer prevention, intensive training efforts must be implemented to develop the next generation of basic and clinical scientists--and physician researchers--capable of working in a cross- and multidisciplinary research environment. Training current researchers in new approaches will add efficiency to their combined research experiences.
    Preview · Article · Feb 2009 · Recent results in cancer research. Fortschritte der Krebsforschung. Progrès dans les recherches sur le cancer
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    ABSTRACT: Celecoxib, a selective inhibitor of cyclooxygenase-2 (Cox-2), was efficacious in clinical prevention trials of patients with familial adenomatous polyposis (FAP) and sporadic colorectal cancer. To identify as yet poorly defined molecular determinants of celecoxib efficacy, a multidimensional serum fractionation approach was used coupled with nanospray tandem mass spectrometry to perform label-free global proteomic profiling of serum samples from the FAP/celecoxib prevention trial. Subsequently, the application of an algorithm for large-scale biomarker discovery on comparative serum proteomic profiles of pre- and post-celecoxib treatment samples identified 83 potentially celecoxib-responsive proteins from various cellular compartments, biological processes and molecular functions. Celecoxib modulation of some of these proteins was confirmed in serum samples of FAP patients and colorectal cancer cell lines by Western blotting. Thus, using a shotgun procedure to rapidly identify important celecoxib-modulated proteins, this pilot study has uncovered novel systemic changes some of which are highly relevant for carcinogenesis and vascular biology. Validation of selected markers, especially those involved in key signaling networks and those considered molecular indicators of cardiovascular pathology, in larger celecoxib clinical trials is expected to provide insights into the molecular mechanisms of celecoxib and the efficacy/toxicity issues related to its use as a chemopreventive agent.
    Full-text · Article · Jan 2009 · Cancer genomics & proteomics
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    ABSTRACT: It is well established that celecoxib, a selective inhibitor of cyclooxygenase-2 (COX-2) and a tested chemopreventive agent, has several COX-2-independent activities. In an attempt to better understand COX-2-independent molecular mechanisms underlying the chemopreventive activity of celecoxib, we did global transcription profiling of celecoxib-treated COX-2-positive and COX-2-deficient colorectal cancer cell lines. Celecoxib treatment resulted in significantly altered expression levels of over 1,000 to 3,000 transcripts in these cell lines, respectively. A pathway/functional analysis of celecoxib-affected transcripts, using Gene Ontology and Biocarta Pathways and exploring biological association networks, revealed that celecoxib modulates expression of numerous genes involved in a variety of cellular processes, including metabolism, cell proliferation, apoptotic signaling, cell cycle check points, lymphocyte activation, and signaling pathways. Among these processes, cell proliferation and apoptotic signaling consistently ranked as the highest-scoring Gene Ontology terms and Biocarta Pathways in both COX-2 expresser and nonexpresser cell lines. Altered expression of many of the genes by celecoxib was confirmed by quantitative PCR and at the protein level by Western blotting. Many novel genes emerged from our analysis of global transcription patterns that were not previously reported to be affected by celecoxib. In the future, in-depth work on selected genes will determine if these genes may serve as potential molecular targets for more effective chemopreventive strategies.
    Preview · Article · Dec 2008 · Cancer Epidemiology Biomarkers & Prevention
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    ABSTRACT: Chemoprevention has been shown to be an extremely promising approach to the prevention of invasive cancer. Through the identification of chemopreventive agents that inhibit or reverse the process of carcinogenesis, new strategies of early intervention can be developed for patients at high risk that potentially prevent the onset of invasive and metastatic phases of cancer. This articles reviews the present efforts in chemoprevention research, including the identification of promising agents, screening, and preclinical and clinical evaluations.
    Preview · Article · Jan 2008 · CA A Cancer Journal for Clinicians
  • Peter Greenwald
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    ABSTRACT: Clifton Leaf, in his article "Why We're Losing the War on Cancer," presents criticisms of past research approaches and the small impact of this research thus far on producing cures or substantially extending the life of many cancer patients. It is true that gains in long-term survival for people with advanced cancers have been modest, hindered in part by the heterogeneity of tumors, which allows the cancers to persist using alternate molecular pathways and so evade many cancer therapeutics. In contrast, clinical trials have demonstrated that it is possible to reduce the incidence or improve cancer survival through prevention and early detection. Strides have been made in preventing or detecting early the four deadliest cancers in the United States (i.e., lung, breast, prostate, and colorectal). For example, 7-year follow-up data from the Breast Cancer Prevention Trial (BCPT) provides evidence that tamoxifen reduces the occurrence of invasive breast tumors by more than 40%; recent studies using aromatase inhibitors and raloxifene are also promising. The Prostate Cancer Prevention Trial (PCPT) showed that finasteride reduced prostate cancer incidence by 25%, and the ongoing Selenium and Vitamin E Cancer Prevention Trial (SELECT) is investigating selenium and vitamin E for prostate cancer prevention based on encouraging results from earlier studies. Living a healthy lifestyle, including regular physical activity, avoiding obesity, and eating primarily a plant-based diet has been associated with a lower risk of colorectal cancer. In addition, noninvasive stool DNA tests for early detection are being studied, which may lessen the reluctance of people to be screened for colorectal polyps and cancer. Behavioral and medical approaches for smoking prevention are ways to reduce the incidence of lung cancer, with antinicotine vaccines on the horizon that may help former smokers to avoid relapse. The US National Lung Screening Trial is testing whether early detection via spiral CT screening will reduce lung cancer mortality. Prevention and earlier detection offer efficient and practical strategies to reduce the cancer burden. Several of the suggestions Mr. Leaf makes, such as developing interdisciplinary collaborations and allocating resources to research earlier in the process of carcinogenesis, have become an integral strategy in the National Cancer Institute's (NCI) approach in the past decade, specifically in the realm of cancer prevention and early detection. For example, an aggressive program to identify biomarkers for earlier detection of cancer--the NCI's Early Detection Research Detection (EDRN)--has identified three promising biomarkers since its establishment in 2000. It collaborates with the National Institute of Standards and Technology and extramural scientists to develop validation standards and to identify the best technologies to use for systematic investigations. If these biomarkers can be validated, they might help to reduce cancer mortality.
    No preview · Article · Feb 2007 · Recent results in cancer research. Fortschritte der Krebsforschung. Progrès dans les recherches sur le cancer
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    ABSTRACT: Approximately 20-30% of Americans consume multivitamin supplements daily, indicating high public interest in the prevention of cancer and other chronic diseases through a nutrition-based approach. Although several bioactive food components, including vitamins and minerals, have been investigated for their ability to affect cancer risk, few large, randomized, placebo-controlled clinical trials of multivitamins with cancer as the primary endpoint have been performed. The results of most large-scale trials of multivitamin supplements (combinations of > or = 2 vitamins and minerals) to prevent cancer have been mixed. The Linxian General Population and Dysplasia trials found a decreased risk of cancer, particularly stomach cancer, for participants taking a multivitamin supplement, but this was in a borderline-deficient population in China. Two trials, the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study and the beta-Carotene and Retinol Efficacy Trial, found an increased risk of lung cancer among male cigarette smokers or asbestos-exposed persons taking beta-carotene-a surprising result, considering that most epidemiologic studies have suggested that consumption of fruit and vegetables appears to lower cancer risk. To clarify the effects of multivitamin supplements, several large randomized clinical trials are underway, including the Physicians' Health Study II, the Selenium and Vitamin E Cancer Prevention Trial, and a European study, Supplémentation en Vitamines et Minéraux Antioxydants (SU.VI. MAX). Because epidemiologic studies generally evaluate foods rather than specific bioactive food components, a systematic approach to determining how combinations of vitamins and minerals may interact to ameliorate cancer risk is necessary to further our understanding of the potential benefits and risks of supplement use.
    Full-text · Article · Feb 2007 · American Journal of Clinical Nutrition
  • Ritva R. Butrum · Peter Greenwald · Paul Talalay

    No preview · Article · Jan 2007
  • Peter Greenwald · John Milner

    No preview · Article · Dec 2006

    No preview · Article · Dec 2006 · Annals of the New York Academy of Sciences
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    ABSTRACT: Celecoxib, a selective inhibitor of the enzyme cyclooxygenase-2 (COX-2), has been shown to be a promising chemoprevention agent. The chemopreventive efficacy of celecoxib is believed to be a consequence of its COX-2-dependent and COX-2-independent effects on a variety of cellular processes including proliferation, apoptosis, angiogenesis, and immunosurveillance. In an attempt to identify proteomic markers modulated by celecoxib that are independent of its inhibitory effect on COX-2, the colorectal cancer cell line HCT-116, a nonexpresser of COX-2, was treated with celecoxib. We used the powerful, state-of-the-art two-dimensional difference gel electrophoresis technology coupled with mass spectrometric sequencing to compare global proteomic profiles of HCT-116 cells before and after treatment with celecoxib. Among the differentially expressed proteins identified following celecoxib treatment were proteins involved in diverse cellular functions including glycolysis, protein biosynthesis, DNA synthesis, mRNA processing, protein folding, phosphorylation, redox regulation, and molecular chaperon activities. Our study presents a comprehensive analysis of large-scale celecoxib-modulated proteomic alterations, at least some of which may be mechanistically related to the COX-2-independent chemopreventive effect of celecoxib.
    No preview · Article · Oct 2006 · Cancer Epidemiology Biomarkers & Prevention
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    ABSTRACT: High-grade prostatic intraepithelial neoplasia (HGPIN) is generally regarded as a premalignant lesion that progresses toward prostate cancer. In light of the significant sequelae of prostate cancer treatment, prevention is desirable, and men with HGPIN would be suitable, high-risk subjects. There is in vitro, in vivo, epidemiologic, and human experimental evidence that selenium supplementation may protect against prostate cancer. This article introduces the rationale for, and progress to date, of a double-blind, randomized, placebo-controlled trial of selenium supplementation (200 mug/d in the form of selenomethionine), to prevent the development of prostate cancer among men with HGPIN. The trial, Southwest Oncology Group Protocol 9917, funded by a National Cancer Institute program supporting pivotal prevention trials has registered 537 patients and has randomized >380 to date. Subject accrual is expected to be completed by the fall of 2006, with trial completion in 2009.
    Full-text · Article · Aug 2006 · Cancer Epidemiology Biomarkers & Prevention

Publication Stats

7k Citations
1,613.44 Total Impact Points


  • 1984-2013
    • National Institutes of Health
      • • Division of Cancer Prevention
      • • Division of Cancer Epidemiology and Genetics
      베서스다, Maryland, United States
  • 1986-2012
    • National Cancer Institute (USA)
      • Division of Cancer Prevention
      베서스다, Maryland, United States
  • 1993-2010
    • NCI-Frederick
      Фредерик, Maryland, United States
  • 1990
    • Fox Chase Cancer Center
      Philadelphia, Pennsylvania, United States
    • Yale University
      • School of Medicine
      New Haven, Connecticut, United States
  • 1981
    • New York State Department of Health
      New York City, New York, United States
  • 1977
    • Albany Stratton VA Medical Center
      Albany, New York, United States
  • 1971
    • Albany Medical College
      • Department of Pathology
      Albany, New York, United States