Letter from the Editor
Greetings Colleagues, We wish you, our esteemed readers and contributors, a happy New Year from all of us here at Cancer Prevention Research (CaPR). It is my pleasure to report on the state of the journal after a very productive and rewarding 2013. As Editor-in-Chief, I am proud of the fact that the journal continues to publish high quality primary papers, perspectives, minireviews and commentaries from clinical and preclinical disciplines within our diverse scope—all helping to shape the field of prevention. In late 2012, we published a groundbreaking study that validated loss of heterozygosity (LOH) profiles in predicting risk of progression to oral cancer in patients with low-grade oral dysplasia (1–3). Building on this and more recent work in the molecular study of premalignancy (4, 5), CaPR senior editor Ignacio Wistuba is heading a new minireview series focused on the early pathogenesis of selected human tumors. Clinical reports in CaPR, which have addressed important public health issues, have received substantial press coverage in 2013. For example, the New York Times (NYT) reported on August 21 on the CaPR report (Bui and colleagues; ref. 6) that demonstrated the significant association between oral health and oral human papillomavirus (HPV) infection and the interactive effects of oral health, smoking, and oral sex on oral HPV infection. Commenting on this first of its kind study in the NYT was our own CaPR board member Maura Gillison, an expert on HPV-induced oropharyngeal cancer. Research like this represents a significant first step, and we are proud to continue to spur important dialogue about behavior and other aspects of cancer prevention in the public health forum. CaPR also published important randomized controlled trials (RCTs). Karen Lu led an RCT to evaluate the effect of oral contraceptives and Depo-Provera on endometrial proliferation in women with Lynch syndrome—the first study of its kind in evaluating agents that might prevent Lynch syndrome–associated endometrial cancer (7). In May, we published a provocative positive RCT of folic acid (FA) in the primary prevention of sporadic colorectal adenoma (CRA) in China (8). These findings stand in contrast to prior negative RCTs of FA supplementation in the secondary prevention of CRA (recurrent adenomas) in different populations (9) and suggest a role for FA in a cohort with a low baseline FA status and without precancerous lesions—underscoring the potential importance of optimal timing of folate intervention. We also published an ancillary gene expression profiling study (in adipose tissue) within a large RCT that examined the biology underlying the relationship between energy balance interventions and cancer in women (10). In addition, CaPR published important negative RCTs (e.g., from doi: 10.1158/1940-6207.CAPR-13-0443 Ó2014 American Association for Cancer Research.
Cancer Prevention Research
the Meyskens and DeCensi groups; refs. 11, 12) and examined the ongoing challenges and opportunities of cancer prevention trials by publishing several perspectives and commentaries on this topic by some of the most established investigators in the field (e.g., Brenner, Hawk, Mulshine, Ondrey, Stoffel, Perloff and Steele; refs. 13–16). To highlight the 50th anniversary of the first report of the Surgeon General’s Advisory Committee on Smoking and Health, AACR has organized and assembled a special compilation of articles representing the scope of each AACR journal. In addition to being distributed as a self-standing publication, there will be a dynamic online component with features such as video interviews. We at CaPR are excited about our contribution to this compendium, as our very own senior deputy editor Eva Szabo and CaPR board member Stephen Hecht have authored a historical perspective describing general progress in this field over the past 50 years and future directions (17). This important work highlights select advances in tobacco carcinogenesis research, including 1) Hecht’s own seminal work on the development of highly specific and quantitative biomarkers of carcinogen and toxicant uptake and metabolism in smokers and nonsmokers exposed to second hand smoke, which played an important role in the development of the pervasive clean air regulations, 2) preclinical and clinical development of promising chemopreventive agents such as iloprost (18, 19), and 3) major standard-of-care changing advances, including helical CT screening. Cancer immunoprevention research has emerged from the fields of tumor immunology and chemoprevention into a robust and novel area of scientific exploration focusing on the exploitation of the crucial role of the immune system during cancer development prior to the invasive phase. Immunoprevention can produce an immunologic memory that calls upon a milieu of intrinsic cells and cytokines whenever a tumorigenic signal emerges. CaPR has been on the cutting edge of this exciting field in recent years and last year was no exception, including a preclinical vaccine study to prevent the progression of preinvasive lesions in a transgenic murine model of spontaneous basal-type breast cancer (20) and an early-phase clinical trial of a MUC1 vaccine in patients with advanced colorectal adenomas (21). CaPR also published provocative reviews this past year by prominent researchers in this field, e.g., Dhodapkar, who posited that both cancer cells and the immune system represent independent and complex systems with plasticity and adaptive potential and that the cross-talk may determine the evolution of both tumors and the host response (22) and the Disis group (Marzbani and colleagues; ref. 23) on the modulation of the human immunosurveillance system by common chemopreventive agents such as aspirin. To highlight this critical emerging field, CaPR is launching a new series of articles focusing on cancer immunoprevention. We are delighted to introduce Asad Umar [Chief, Gastrointestinal & Other Cancers Research Group, Division of Cancer
Letter from the Editor
Prevention, National Cancer Institute (NCI), Bethesda, MD] as our guest editor for this exciting series. We also continue to publish important preclinical discoveries, including a novel combinatorial nanotechnologybased chemopreventive regimen to suppress neoplastic pancreatic lesions (24), studies of energy balance effects on Kras signaling in early pancreatic neoplasia (25, 26), novel AMPK-independent preventive effects of metformin in lung tumorigenesis (27), and studies of social isolation, metabolic gene reprogramming and mammary tumors (28). We continue to publish major discoveries in prostaglandin (PG) biology in cancer prevention that began with the first study of PG transporters in neoplasia from the DuBois group in one of the earliest issues of the journal (Holla and colleagues; ref. 29), which was highlighted in an insightful perspective by Sanford Markowitz (30). In April, we published a novel study of PG biology in gastric carcinogenesis, which reported that H. pylori infection downregulates 15-hydroxyprostaglandin dehydrogenase (15-PGDH) expression in endoscopic biopsies, an effect that was reversible after H. pylori-eradication therapy; in vitro
mechanistic studies revealed that this effect is mediated by TLR4-MyD88-ERK1/2 or EGFR activation leading to Snail transcriptional derepression of 15-PGDH expression (31). In closing, I thank you, our valued readers and contributors, for your ongoing interest in and submissions to CaPR. Looking forward, we are delighted about the transdisciplinary assortment of thought-provoking and innovative contributions to the field of cancer prevention that will appear in the pages of CaPR in 2014. Because of you, we are able to bring the highest impact cancer prevention science to readers worldwide. With best wishes for 2014,
Scott M. Lippman, M.D. Editor-in-Chief Received December 30, 2013; accepted December 30, 2013; published OnlineFirst January 24, 2014.
Zhang L, Poh CF, Williams M, Laronde DM, Berean K, Gardner PJ, et al. Loss of heterozygosity (LOH) proﬁles—validated risk predictors for progression to oral cancer. Cancer Prev Res 2012;5:1081–9. 2. Cavenee WK. Genetic driver events in premalignancy: LOH validated for marking the risk of oral cancer. Cancer Prev Res 2012;5:1073–4. 3. Burgess DJ. Biomarkers: genetic predictors of oral cancer risk. Nat Rev Cancer 2012;12:659. 4. Kadara H, Shen L, Fukimoto J, Saintigny P, Chow C-W, Lang W, et al. Characterizing the molecular, spatial and temporal ﬁeld of injury in early-stage smoker non-small cell lung cancer patients after deﬁnitive surgery by expression proﬁling. Cancer Prev Res 2013;6:8–17. 5. Bartley AN, Parikh N, Hsu C-H, Roe DJ, Buckmeier JA, Corley L, et al. Colorectal adenoma stem-like cell populations: associations with adenoma characteristics and metachronous colorectal neoplasia. Cancer Prev Res 2013;6:1162–70. 6. Bui TC, Markham CM, Ross MW, Mullen PD. Examining the association between oral health and oral HPV infection. Cancer Prev Res 2013;6:917–24. 7. Lu KH, Loose DS, Yates MS, Nogueras-Gonzalez GM, Munsell MF, Chen L-M, et al. Prospective multicenter randomized intermediate biomarker study of oral contraceptive versus Depo-Provera for prevention of endometrial cancer in women with Lynch syndrome. Cancer Prev Res 2013;6:774–81. 8. Gao Q-Y, Chen H-M, Chen Y-X, Wang Y-C, Wang Z-H, Tang J-T, et al. Folic acid prevents the initial occurrence of sporadic colorectal adenoma in Chinese older than 50 years of age: a randomized clinical trial. Cancer Prev Res 2013;6:744–52. 9. Cole BF, Baron JA, Sandler RS, Haile RW, Ahnen DJ, Bresalier RS, et al. Folic acid for the prevention of colorectal adenomas: a randomized clinical trial. JAMA 2007;297:2351–9. 10. Campbell KL, Foster-Schubert KE, Makar KW, Kratz M, Hagman D, Schur EA, et al. Gene expression changes in adipose tissue with dietand/or exercise-induced weight loss. Cancer Prev Res 2013;6:217–31. 11. Armstrong WB, Taylor TH, Kennedy AR, Melrose RJ, Messadi DV, Gu M, et al. Bowman birk inhibitor concentrate and oral leukoplakia: a randomized phase IIb trial. Cancer Prev Res 2013;6:410–8. 12. Puntoni M, Branchi D, Argust A, Zanardi S, Crosta C, Meroni E, et al. A randomized, placebo-controlled, preoperative trial of allopurinol in subjects with colorectal adenoma. Cancer Prev Res 2013;6:74–82.
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13. Brenner DE, Hawk E. Trials and tribulations of interrogating biomarkers to deﬁne efﬁcacy of cancer risk reductive interventions. Cancer Prev Res 2013;6:71–3. 14. Mulshine JL, Ondrey FG. Not signiﬁcant but important. Cancer Prev Res 2013;6:371–4. 15. Stoffel EM, Walsh C. Chemoprevention of endometrial cancer in Lynch syndrome: a step forward. Cancer Prev Res 2013;6:755–9. 16. Perloff M, Steele VE. Early-phase development of cancer prevention agents: challenges and opportunities. Cancer Prev Res 2013;6:379–83. 17. Szabo E, Hecht S. Fifty years of tobacco carcinogenesis research: from mechanisms to early detection and prevention of lung cancer. Cancer Prev Res 2014;7:1–8. 18. Keith R, Blatchford PJ, Kittelson J, Minna JD, Kelly K, Massion PP, et al. Oral iloprost improves endobronchial dysplasia in former smokers. Cancer Prev Res 2011;4:793–802. 19. Mascaux C, Feser WJ, Lewis MT, Baron AE, Coldren CD, Merrick DT, et al. Endobronchial miRNAs as biomarkers in lung cancer chemoprevention. Cancer Prev Res 2013;6:100–8. 20. Disis ML, Gad E, Herendeen DR, Phan-Lai V, Park KH, Cecil DL, et al. A multiantigen vaccine targeting neu, IGFBP-2, and IGF-IR prevents tumor progression in mice with preinvasive breast disease. Cancer Prev Res 2013;6:1273–82. 21. Kimura T, McKolanis JR, Dzubinski LA, Islam K, Potter DM, Salazar AM, et al. MUC1 vaccine for individuals with advanced adenoma of the colon: a cancer immunoprevention feasibility study. Cancer Prev Res 2013;6:18–26. 22. Dhodapkar MV. Personalized immune-interception of cancer and the battle of two adaptive systems—when is the time right? Cancer Prev Res 2013;6:173–6. 23. Marzbani E, Inatsuka C, Lu H, Disis ML. The invisible arm of immunity in common cancer chemoprevention agents. Cancer Prev Res 2013;6:764–73. 24. Grandhi BK, Thakkar A, Wang J, Prabhu S. A novel combinatorial nanotechnology-based oral chemopreventive regimen demonstrates signiﬁcant suppression of pancreatic cancer neoplastic lesions. Cancer Prev Res 2013;6:1015–25. 25. Lashinger LM, Harrison LM, Rasmussen AJ, Logsdon CD, Fischer SM, McArthur JM, et al. Dietary energy balance modulation of Krasand Ink4a/Arfþ/ -driven pancreatic cancer: the role of insulin-like growth factor-I. Cancer Prev Res 2013;6:1046–55.
Cancer Prevention Research
Letter from the Editor
26. Dawson DW, Hertzer K, Moro A, Donald G, Chang H-H, Go VL, et al. High-fat, high-calorie diet promotes early pancreatic neoplasia in the conditional KrasG12D mouse model. Cancer Prev Res 2013;6:1064–73. 27. Quinn BJ, Dallos M, Kitagawa H, Kunnumakkara AB, Memmott RM, Hollander MC, et al. Inhibition of lung tumorigenesis by metformin is associated with decreased plasma IGF-I and diminished receptor tyrosine kinase signaling. Cancer Prev Res 2013; 6:801–10. 28. Volden PA, Wonder EL, Skor MN, Carmean CM, Patel FN, Ye H, et al. Chronic social isolation is associated with metabolic gene expression
changes speciﬁc to mammary adipose tissue. Cancer Prev Res 2013; 6:634–45. 29. Holla VR, Backlund MG, Yang P, Newman RA, DuBois RN. Regulation of prostaglandin transporters in colorectal neoplasia. Cancer Prev Res 2008;1:93–9. 30. Markowitz, SD. Colorectal neoplasia goes with the ﬂow: prostaglandin transport and termination. Cancer Prev Res 2008;1:77–9. 31. Ryu Y-M, Myung S-J, Park YS, Yang D-H, Song HJ, Jeong J-Y, et al. Inhibition of 15-hydroxyprostaglandin dehydrogenase by Helicobacter pylori in human gastric carcinogenesis. Cancer Prev Res 2013;6:349–59.
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