To each and every one of our esteemed readers and contributors, Happy New Year! from all of us at Cancer Prevention Research (CaPR). We are very excited about the host of stimulating, pioneering contributions to the field of cancer prevention that will appear in the pages of CaPR in 2013. CaPR has evolved to become a compact collection of high-quality work from diverse clinical and preclinical disciplines within each issue of the journal, making us a transdisciplinary venue where our readers can easily gain access to articles that may attract interest even though they fall outside their specific area of interest and expertise. This diversity speaks to the importance of CaPR, now in its sixth year, and its evolving role in the cancer prevention research community. And for this, we are very grateful. The following are but a few examples of outstanding contributions to our journal in 2012.
Our highest impact article of 2012 was a groundbreaking article by the Miriam Rosin group (1) involving molecular pathology and carcinogenesis; they reported the prospective, definitive validation of specific loss of heterozygosity (LOH) profiles as genetic drivers in premalignancy and as biomarkers of the risk of oral cancer. The journal Nature Reviews Cancer highlighted this study and its findings that the LOH status of chromosomes 3p and 9p in patients with low- to moderate-grade oral dysplasia can reliably differentiate higher and lower risks of progression to oral cancer (2). This study is crucial for improving targeted prevention for high-risk patients while sparing low-risk patients from aggressive monitoring and treatment. The importance of this genetic finding was underscored by a high-profile companion Perspective written by Web Cavenee (Director, Ludwig Institute for Cancer Research at the University of California, San Diego, CA; ref. 3), whose laboratory made the groundbreaking discovery of LOH and the existence of tumor suppressor genes that paved the way for the Rosin work.
Now in this issue of the journal, we are pleased to feature another important report involving molecular pathology and carcinogenesis, one that is sure to be another high-impact article. Ignacio Wistuba and colleagues report their novel findings that in the molecular field of injury of early-stage non–small cell lung cancer patients after definitive surgery, there are spatial and temporal cancer-associated alterations in certain gene expression profiles, functional gene networks, and oncogenic protein kinase activation in airway sites adjacent to tumors (4). As highlighted by an insightful Perspective penned by leaders in the lung cancer prevention field including Avrum Spira and Steve Dubinett (5), the Wistuba study reflects a technical tour de force that allows unprecedented characterization of the field of cancerization by comparing these cancer-associated modulations in the airways adjacent to the tumor to brushings from the main carina and contralateral airways. This work applies emerging high-throughput technologies to the study of histologically normal and premalignant tissue and thus sheds light on unprecedented opportunities to characterize and target the molecular networks that drive early carcinogenesis and to identify novel biomarkers of cancer risk—advances that promise to influence all aspects of cancer prevention.
My January 2012 Letter from the Editor highlighted a group of articles in that issue of the journal that dealt with international clinical prevention in developing countries (6); 4 of these articles focused on global prevention with vaccines and screening against infection-related cancers, including a report on the mechanisms by which coinfection with human papillomavirus and HIV, which is prevalent in developing places such as Haiti and sub-Saharan Africa, cause a very high risk of cervical cancer (7). One of the international primary articles and its companion Perspective addressed the challenge and promise of translating a natural product (lyophilized strawberry powder) into a clinical/translational trial in the setting of esophageal dysphagia in the poorest rural farming region of China (8, 9).
The April 2012 issue of the journal featured a series of preclinical research articles and 2 perspectives on metformin, including a cutting-edge report from the Michael Pollak group on their discovery of a novel, AMPK-independent mechanism of metformin involving mitochondrial reactive oxygen species (10). I highlighted this series of articles in a special Letter from the Editor (also in the April issue) because of the tremendous interest in and promise of metformin, already the most widely used antidiabetic drug in the world, for cancer prevention (11). These articles add substantially to the published body of work on metformin for cancer prevention, which includes several articles that have appeared previously in our journal. In the December 2012 issue, in their innovative report on bioanalytic methods applied to metabolism, the Andrew Dannenberg group first described the metabolomics landscape of cancer prevention, with a focus on colorectal tumors and associated biofluids and insights into potential metabolic drivers of colorectal cancer (12). Specifically, this group identified a fecal metabolomic signature that reflected experimental colorectal tumor burden. This trendsetting, noninvasive approach for early detection of neoplasia is now primed for clinical testing. This study and the accompanying Perspective by Christian Metallo highlight the expanding role of cancer metabolomics in the field of cancer prevention and early detection research and will open new avenues and drive future validation studies for the noninvasive analysis of colorectal and other neoplasias (13). We also published several primary articles on obesity, energy balance, and cancer, including preclinical studies documenting beneficial effects of caloric restriction on epithelial–mesenchymal transition and in preventing aggressive “basal” breast cancer subtypes (14) and clinical reports, such as the differential influence of body mass index (BMI) on pre- and postmenopausal breast cancer within the landmark National Surgical Adjuvant Breast and Bowel Project (NSABP) P1 and P2 trials (15). We featured natural agent-related studies, including several early-phase clinical trials and provocative preclinical articles, such as a study from the Karen Liby group of a triterpenoid in delaying the development of mammary cancer in mutant BRCA1 mice (16). Highlighting the diversity of prevention work published this past year in CaPR, other provocative primary reports include one on the effects of modifying gut microbiotica to prevent viral hepatitis and liver cancer (17), another on hops extracts to prevent mammary cancer (18), and one on pathway activation mapping and networks analyses in human skin premalignancy progression (19).
Our coverage of prevention-related imaging was strong in 2012. The Ann Gillenwater group combined wide-field and high-resolution optical imaging techniques in a multimodal approach enabling detection of oral premalignant lesions with both high sensitivity and high specificity (20). The Rebecca Richards-Kortum group clinically tested low-cost, high-resolution microendoscopy for early detection of cervical neoplasia in Shanki Province, China (21). Finally, The Sushmita Mukherjee group conducted a novel, comprehensive study of multiphoton microscopy in mouse models of colitis and colorectal neoplasia, in human subjects (ex vivo) with celiac sprue, inflammatory bowel disease, and colorectal cancer, and in anesthetized rats (in vivo; ref. 22). This breakthrough in imaging technology provides unprecedented opportunities to characterize early carcinogenesis and to identify novel biomarkers of cancer risk—advances that promise to facilitate early detection and cancer prevention.
In the October 2012 issue of the journal, the Edward Nelson group reported their provocative study within a randomized clinical trial showing that interventions reducing psychosocial distress can lengthen telomeres in peripheral blood mononuclear cells; longer telomere length has been associated in other studies with younger age and reduced heart disease and cancer (23). This new study builds on exciting work of Nobel Laureate Elizabeth Blackburn and Elisa Epel that is summarized in a related Minireview in the same issue of the journal (24). This minireview posits that modifiable predictors such as prenatal conditions, early adversity, current stress, and lifestyle, are causal factors in telomere shortening, and argues that there is a tremendous opportunity for behavioral intervention to improve maintenance and elongation of telomeres (24).
We continue to publish cutting-edge Perspectives by world-renowned research leaders to accompany selected primary articles. In 2012, we complemented our portfolio of reviews, beginning with a review by the Ron Evans group on nuclear receptors as modulators of the tumor microenvironment in the January 2012 issue (25). In the November 2012 issue, we published a comprehensive review on cancer-related obesity and energy balance, authored by several leaders in the field including Nathan Berger (14) as well as other reviews focused on various aspects of this important public health issue.
Before closing, I give heartfelt thanks to new CaPR Senior Deputy Editors Timothy Wang, Ernie Hawk, and Eva Szabo. These colleagues and friends stepped into expanded deputy editor roles in order to facilitate and expedite editorial decisions as I learn the ropes of my new job as director of the UC San Diego Moores Cancer Center. Their vast and combined expertise also have broadened the journal's editorial perception of readers' interests and the utility and general impact of work that comes before us—benefits that help us maintain the objectivity and high standards of the journal. To Tim, Ernie, and Eva—your hard work and commitment to the journal are exemplary and indispensable. I feel no less gratitude for the continued, vital contributions of our exceptional other Deputy Editors, Senior Editors, Statistical Editors, and Editorial Board members. You make the enterprise of “team-science” publishing as enjoyable for me, and as rich for our readers, as anyone has a right to ask.
In closing, I thank you, our valued readers and contributors, for your ongoing interest in and submissions to CaPR. Because of you, CaPR is able to bring the highest quality, originality, and importance of cancer prevention science to readers worldwide. As evidenced by these few examples of our exceptional year of publications, we remain committed to procuring and publishing the highest impact research that advances the field of cancer prevention.
Best wishes for 2013,
Scott M. Lippman, MD
Editor-in-Chief
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