Dear Colleagues,
Welcome to the inaugural issue of Cancer Prevention Research (CaPR). Working on the mission of CaPR—to address the current state of cancer prevention and how CaPR will advance and catalyze our field through this and future issues—has led me to reflect on my own journey as a scientist publishing cancer prevention research in many diverse journals. Although important papers on cancer prevention certainly will continue to appear in other great journals, my personal experience with the cancer prevention literature highlights for me the importance of CaPR—a journal that is devoted exclusively to cancer prevention research and where I can easily and routinely “tune in” to the latest, greatest thinking about our field—what a resource! And what a privilege it is for me to be able to offer this Letter as one of the first commentaries to appear in CaPR.
In many ways, cancer prevention research was very different when I began working in this field 22 years ago. Back then, chemoprevention trials were mainly clinical (translational work was just beginning); cancer risk mainly involved classic epidemiologic assessments; mouse modeling mainly involved induction of tumors with carcinogens; the term “clonal” applied to cancer, almost never premalignancy; and the various nascent disciplines of cancer prevention toiled mainly in isolated pockets with little interdisciplinary collaboration and/or synergy. Major advances of the past two decades include the concept of intraepithelial neoplasia (IEN), molecular cancer risk assessment, and the strong convergence of multiple prevention fields and disciplines. There have been striking technological advances including new molecular tools and methods that have fundamentally changed the way we view premalignancy and carcinogenesis, teaching us that premalignancy is not monolithic but a complex heterogeneous process involving tissue injury, genetic and epigenetic alterations, signal transduction abnormalities, clonal patches, the microenvironment, inflammation, angiogenesis, and other molecular processes that either were not known to exist or were not considered to be relevant to premalignancy (or cancer). Another major technological advance is the increasing sophistication of genetically engineered mouse models. There also have been major advances in statistical modeling and bioinformatics relating to all aspects of cancer prevention including risk assessment and early detection. Emerging research in genomics and neuroscience is revolutionizing our understanding of behavior, as well as the complex interactions between genes, behavior, and the social environment. These advances are shaping translational research on behavioral cancer prevention approaches. Studies conducted by surgeons and other specialists have confirmed that excision of IEN and organ removal (usually in very high-risk patients with inherited cancer predisposition syndromes) can lead to effective cancer prevention, as can the newer approach of photodynamic therapy.
Clearly, prevention concepts and technologies have advanced tremendously on many fronts over the past two decades, bringing greater attention and focus to the field. As a result, molecular cancer prevention has moved from an exciting hypothesis to a proven clinical reality. This reality has been demonstrated in several successful trials that have challenged, changed, and/or validated clinical practices in risk assessment and risk reduction, leading to regulatory approval of many drugs and devices (including HPV vaccine, tamoxifen, raloxifene, celecoxib, BCG, valrubicin, diclofenac, topical 5-fluorouracil, masoprocol, photosensitizers combined with photodynamic therapy, fecal immunochemical and DNA-based tests) to characterize and then reduce cancer risk and/or treat IEN.
The duty and promise of CaPR is to bring you leading-edge, original research in all areas of modern cancer prevention science and practice, along with perspectives and commentaries that will stimulate new thinking in the field. This goal is reflected in the following scientific scope:
Cancer Prevention Research, the newest scientific journal from the American Association for Cancer Research, is devoted exclusively to cancer prevention research. The journal publishes important original articles, reviews, and perspectives in the major topic areas of oncogenesis, risk factors and risk assessment, early detection research, and chemoprevention and other interventions including the basic science behind them. Cancer Prevention Research comprises preclinical, translational, and clinical research, with special attention on molecular discoveries and on building a translational bridge between the basic and clinical sciences related to cancer prevention.
The exciting articles in this and other early issues exemplify the breadth, depth, and translational and cross-disciplinary thrust of CaPR. We lead off this inaugural issue with two seminal articles on colorectal cancer chemoprevention. Investigators of the Bertagnolli group provide translational insights gained from the landmark Adenoma Prevention with Celecoxib trial that answer the question of whether aberrant crypt foci can be a surrogate end point biomarker for colorectal cancer prevention. Meyskens, Gerner, and colleagues report the dramatic phase III activity of combined difluoromethylornithine and sulindac in preventing sporadic colorectal adenomas. A breakthrough article by the Mao group reports a novel, noninvasive method of potentially identifying smokers at highest risk of lung cancer by assessing molecular alterations in the oral cavity. The Spira group reports a novel clinicogenomic model for early lung cancer detection. This model may also be useful in assessing lung cancer risk, thus illustrating the merging boundaries between molecular early cancer detection and risk assessment. These articles of the Mao and Spira groups reflect the major CaPR interest in focusing on cancer risk and early detection toward improving clinical cancer prevention and its convergence with earliest (ideally subclinical) cancer treatment. Transcription factors in cancer prevention are the topic of a major article by the Brown group, who report their work in targeting AP-1 transactivation in attenuating estrogen receptor–negative mammary carcinogenesis in a trigenic mouse model. The DiGiovanni and Hursting groups report their novel and comprehensive animal model studies of the effects of dietary energy balance (specifically, diet-induced obesity and caloric restriction) on cell signaling pathways. This mechanistic analysis identified insulin-like growth factor-1 receptor, epidermal growth factor receptor (EGFR), and downstream signaling involving Akt, mammalian target of rapamycin, Src, and cyclin D1 as potentially important targets for disrupting the obesity-cancer link.
An important commentary by Blaser on the worldwide threat of infection-related cancers reflects the commitment of CaPR to inviting consideration, commentary, and debate over diverse topics of fundamental importance to prevention's future. This commentary elucidates the complexity of the human microbiome in cancer risk and prevention (illustrated, for example, by Helicobacter pylori research). Perspective articles by world leaders in their fields will accompany and complement selected primary reports. These perspectives will be less companion editorials and more high-profile “thought pieces” that set the leading edge original articles they accompany within the larger context of their fields. This thoughtfulness is illustrated extremely well in this inaugural issue of CaPR by authors Lance and Hamilton (perspective on colorectal aberrant crypt foci), Sporn and Hong (on combination chemoprevention), and Sidransky (on molecular markers of lung carcinogenesis and potentially cancer risk that can be assessed in surrogate oral tissue). These perspectives are exciting, creative works in themselves, and I believe that you will enjoy reading them every bit as much as we enjoy publishing them.
Rest assured that the high quality and diversity of prevention research in this issue of the journal will carry forward into our forthcoming issues and beyond. In addition, for the foreseeable future, all accepted CaPR articles will be published on line as soon as they are available in journal format (and generally before appearing in a print issue). Our spectacular line up of forthcoming articles includes a comprehensive and elegant laboratory report by the DuBois group in colorectal neoplasia, which is the first report of the role of the prostaglandin transporter in any carcinogenesis setting and provides major new insights into the role, regulation, and targeting of prostaglandin transport. The effects of tobacco smoke on global gene expression are reported by the Weinstein and Dannenberg groups in oral premalignancy (in vitro) and by the Zhang and Mao group in lung carcinogenesis (in clinical samples). Both of these articles provide new insights into the molecular mechanisms underlying carcinogenic effects and complex adverse interactions of tobacco smoke with preventive or therapeutic drugs. The Spitz group has contributed two lung cancer risk model articles, one on host genetic factors integrated with clinical-epidemiologic risk factors and the other on risk modeling in African Americans. The merging of the boundaries between cancer therapy and cancer prevention is reflected in reports by the Kurie and Wistuba groups. Results of the Kurie group suggest that autocrine loops may be a major mechanism of EGFR deregulation in lung carcinogenesis and support further studies of EGFR ligands as targets of therapy and prevention in this setting. The Wistuba group identified the timing of EGFR mutations in the sequence of events from preinvasive to metastatic lung disease. We will publish another article on transcription factors in cancer prevention by the Kong group, which reports an important advance in targeting Nrf2 for preventing inflammation-associated cancer. The Jones group describes the striking chemopreventive activity of a novel oral demethylating agent in an APCmin mouse model of intestinal adenomas.
Two very important articles present the latest analytical insights into whether finasteride influenced the development of high-grade prostate cancer and clinically significant disease of any grade in the Prostate Cancer Prevention Trial (PCPT). A group led by Lucia and Thompson reports an exhaustive pathologic review of PCPT cancer specimens that answers the question of whether finasteride prevented mainly clinically significant or clinically insignificant prostate cancer. A group led by Redman and Thompson reports comprehensive statistical modeling that controlled for the biases introduced by finasteride in cancer detection by biopsy during the PCPT. A major component of these analyses was to calculate true high-grade cancer rates based on prostatectomy results in the subgroup of PCPT men who underwent a radical prostatectomy for prostate cancer. Another article on a different statistical modeling approach based on the PCPT was contributed by the Pinsky group, whose findings were consistent with those of Redman and colleagues.
Special features of CaPR are health policy articles and minireviews. Grabowski and Moe report with profound insight on how regulatory, economic, and patent policies affect chemopreventive drug research and development, including lessons learned from the development of the recently Food and Drug Administration–approved preventive agents HPV vaccine and raloxifene. An elegant minireview by Abate-Shen and colleagues discusses the evolution of genetically engineered mouse models from simple transgenics to complex conditional and inducible models, highlighting their potential for cancer prevention research. An important function of CaPR minireviews will be to attract researchers in the fields of review to publish their work in CaPR. The expert authors of forthcoming Perspective articles include Markowitz (on prostaglandin transport and termination), Issa (on the intersection of prevention with epigenetics), Colburn and Kensler (on targeting transcription factors), Penning and Lerman (on the genomics of smoking exposure in relation to drug interactions), Gazdar and Minna (major mechanisms of deregulated epidermal growth factor receptor signaling in lung carcinogenesis and their implications), and Logothetis and Schellhammer (high-grade prostate cancer and clinically significant prostate cancer of any grade in the PCPT).
The aforementioned research, commentary, policy, perspective, and minireview articles are merely a sample of the great work CaPR has lined up for publication over the next several months. Most of these articles have already been published on line (http://cancerpreventionresearch.aacrjournals.org/) and are available for reference and citation.
The scope and philosophy of CaPR will reflect the entire field of cancer prevention. The topics highlighted in this Letter do not imply the exclusion of any part of the current spectrum of cancer prevention research and practice involving every relevant disease site, population, model, mechanism, target, and intervention. Furthermore, CaPR will strive to serve as the best home for future, emerging science that promises to extend the current conceptual and practical boundaries of prevention. A major function of CaPR is to build a bridge between the basic and clinical sciences of prevention. This bridge will allow laboratory scientists and clinical trialists to visit each other's work and thus develop the best science for advancing the control of cancer through prevention. As this description implies, translational research will be a major focus of this new journal, highlighting the work that synthesizes basic and clinical research and the value that this synthesis brings to the field. As examples, the exciting articles in this inaugural issue conform to the vision and mission of CaPR, and future issues will present articles of the same quality and purpose.
In conclusion, let me reaffirm our commitment to make everyone who is interested in cancer prevention feel at home in the pages of Cancer Prevention Research. Cancer prevention has matured and deepened its role in the science and practice of oncology, and CaPR is very pleased to help recognize this success by publishing data from leading research groups throughout the world. Serving as the founding editor-in-chief is a gratifying labor of love and has helped renew my profound awe and appreciation for the many investigators working so hard and creatively in our field. If this Letter conveys a small portion of the excitement and importance of the work contained in this and future issues of CaPR, then I will have done my job.
Last, I would like to thank everyone who has helped CaPR to grow from a concept into a fully fledged member of the family of AACR journals. This diverse, talented group of benefactors includes every author whose outstanding work appears in this first issue; the Deputy and Senior Editors and Editorial Board of CaPR; and the highest leadership and editorial and production staffs of AACR, without whose help I could not function as editor-in-chief. Of course, without you, the readers and contributors, CaPR would not be possible, and so I want to express my profound thanks to you for contributing to its development and success. I look forward to reading and publishing the exciting papers that will appear on the future pages of this magnificent new AACR journal.
With best wishes for interesting, fulfilling reading,
Scott M. Lippman
Editor-in-Chief
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