Dear Colleagues,
It is my pleasure to wish you, our esteemed readers and contributors, a Happy New Year and to report on the state of the journal after a very productive 2011. Thanks to you, the role of Cancer Prevention Research (CaPR) in the cancer prevention research community has continued to grow, as reflected by the substantially increasing numbers of submitted manuscripts we have received over the past couple of years. We went from 262 submissions in 2009 to 399 in 2010 (50% increase) to about 600 in 2011, more than a 200% increase since 2009. Besides keeping us very busy, this “biofeedback” within a wide range of clinical and preclinical topics and disciplines lets us know that the journal has become important to the cancer prevention community.
Clinical CaPR articles of 2011 with a high scientific impact include a randomized controlled trial (RCT) indicating that the prostacyclin analogue iloprost was significantly active in former smokers with endobronchial dysplasia, the most promising result to date for cancer chemoprevention in the lung (1). An RCT of celecoxib suppressed Ki67 in former smokers and suggested that the ratio of COX-2 to 15PGDH mRNA in bronchioalveolar lavage predicted response (2). C-reactive protein predicted harmful cardiovascular effects of celecoxib within the large Adenoma Prevention with Celecoxib (APC) trial (3). The International CAPP trial of aspirin in familial adenomatous polyposis (4) and the SWOG-coordinated Intergroup trial of selenium in high-grade prostatic intraepithelial neoplasia (5) are the largest phase III RCTs in these settings. A large study in the WHI (6) showed that physical activity reduced breast cancer and all-cause mortality in breast cancer survivors. The first large study of predictors of adherence to chemoprevention took place in the NSABP-coordinated Breast Cancer Prevention Trial (P1) of tamoxifen (7). Other CaPR articles in 2011 described early detection work in human papilloma virus (HPV)-related head and neck cancer (a growing epidemic) with an oral “Pap-test equivalent” (8); a systematic, large-scale comparison of the most-promising biomarkers for ovarian cancer early detection within the PLCO Screening Trial (9); and a phase 0 trial involving an oral Akt inhibitor, the first phase 0 trial in chemoprevention (10). CaPR also published clinical/translational reports on the detection of methylated HPV genes in serum and saliva; comprehensive modeling of the health benefits and cost-effectiveness of genetic screening for Lynch syndrome in the general population; an epigenetics study finding somatic inactivation of the BRCA1 promoter in the setting of BRCA1-associated breast cancer; two studies of the effects of supplementation with or dietary depletion of folate on inflammation, immune response, and other molecular pathways in the human colorectum; and five successful translations of preclinical data on complex food/natural products into early-phase clinical/translational testing, including the first phase II trial of curcumin and four randomized trials respectively of micronized resveratrol, broccoli sprout (sulforaphane) beverage, ginger root extract, and fish oil.
Preclinical work reported in CaPR in 2011 includes the first study linking obesity, breast inflammation, and cancer in mice (11), which was confirmed in women; a novel molecular imaging study of inflammation and carcinogenesis (12); and in vitro and in vivo studies of vitamin D3 effects on the Hedgehog target gene Gli1 in murine basal cell carcinomas (13). An elegant mechanistic report showed that the green tea flavonoid epigallocatechin gallate (EGCG) directly bound to the peptidyl prolyl cis/trans isomerase Pin1, which is required for EGCG effects on cell growth, c-Jun activation, and transcription regulation mediated by NF-κB and AP-1 (14)—work that set a new bar for the future study of natural products. Other preclinical CaPR reports of 2011 include mechanistic studies of caloric restriction, rapamycin, and IGF1 signaling in mouse models of pancreatic cancer; a study finding synthetic triterpenoid activity in mutant BRCA1 breast cancer cells and later confirmed in vivo; the finding that estrogens reduce gastric cancer risk by modulating leukocyte recruitment (e.g., via CXCL1) in Heliobacter pylori–infected mice; and the finding by two independent groups that long-term nicotine replacement therapy is relatively safe, which has important public health implications.
The foregoing articles reflect a spectrum of primary research from exciting preclinical work to novel early-phase clinical/translational trials to late-phase clinical studies. CaPR also published high-profile thought pieces over the past year, including a health policy article by Robert Temple (Director of the Office of Medical Policy for CDER of the FDA) on chemopreventive drug development based on the cardiovascular disease–prevention model (15) and commentaries by Elizabeth Blackburn (on the novel prevention concept of cancer interception; ref. 16) and by Gold and colleagues highlighting the flow of novel technology, targets, and drugs from cancer/therapy to premalignancy/-prevention and coining the term “reverse migration” for this process (17). We launched a new section entitled Insight, which features articles that incorporate original, fresh, and creative insights based largely on the previously published research of the author or authors in a topic area of current interest in cancer prevention; Mark Taketo contributed the first Insight article, discussing late-stage invasion/metastasis prevention and featuring his recent work on Notch signaling (18), followed by Jordan and Ford in writing about a paradoxical clinical effect of estrogen on breast cancer risk (19). We continue to publish cutting-edge companion Perspectives (to selected primary papers) by world-renowned research leaders, and we have increased our portfolio of reviews and Minireviews with, for example, articles involving authors Sood and Lutgendorf (on stress and anoikis; ref. 20); Denlinger and Engstrom (on the impact of physical activity on colorectal cancer survivorship; ref. 21), and Chen and White (on autophagy; ref. 22).
In 2011, CaPR added editorial leadership in areas of increased focus and emphasis including international clinical studies, genomics and molecular pathology, and the tumor microenvironment and stem cells, all areas CaPR will explore in 2012 and beyond. Six papers appearing in this issue of the journal report on international clinical prevention in developing countries. Involving authors Lowy, Kane, Vermund, and Fitzgerald, four of these papers discuss global prevention with vaccines and screening against infection-related cancers, highlighting cervical cancer and the mechanisms by which co-infection with HPV and HIV, which is prevalent in developing places such as Haiti and sub-Saharan Africa, cause a very high risk of cervical cancer. The two other international papers, a primary paper and its companion Perspective, address the double-barrel challenge of translating a natural product (lyophilized strawberry powder in this case) into a clinical/translational trial (a promising randomized phase II trial in esophageal dysplasia) and doing so in the poorest rural farming region of China. Emerging technology such as next-generation sequencing platforms for whole-genome and transcriptomic profiling provides unprecedented opportunities to characterize and target the molecular networks that drive early carcinogenesis and to identify novel biomarkers of disease risk—advances that promise to influence all aspects of cancer prevention. A recent article in this direction reported the first study of next-generation sequencing (RNA seq) in human lung carcinogenesis. Last but not least, the journal will publish articles that further explore the tumor microenvironment, stem cells, and the “premalignant niche,” beginning with a review by the Ron Evans group on nuclear receptors and the microenvironment.
And so, I will end where I began, thanking you, valued readers and contributors, for the robust growth of interest in, submissions to, and quality of CaPR. We are thrilled to chart a course along the exciting directions of increased focus outlined above. And of course, we will continue to ply the ever-fascinating ocean of high-impact research in our classic topic areas. Welcome aboard CaPR for 2012, with all of its promise and hope for advancing cancer prevention.
With best wishes for 2012,
Scott M. Lippman, M.D.
Editor-in-Chief
RSS Feeds