Abstract
Pancreatic cancer has a poor prognosis and is often diagnosed at an advanced stage, which makes it difficult to treat. The low survival rate of patients with pancreatic cancer points towards an increased need for novel therapeutic and chemopreventive strategies and also early detection of this disease. Increased consumption of fruits and vegetables has been associated with a reduced risk of pancreatic cancer. Synthetic and natural, diet-derived bioactive compounds have been evaluated as pancreatic cancer chemopreventive agents and have demonstrated various degrees of efficacy in cellular and in vivo animal models. Some chemopreventive agents (for example, curcumin or resveratrol) have also been reported to sensitize pancreatic cancer cells to standard chemotherapeutic drugs (for example, gemcitabine or erlotinib), which suggests that chemopreventive agents could potentially be used as potentiators of standard chemotherapy. Few clinical trials of pancreatic cancer chemopreventive agents have been completed and some are in early phases. Further development of pancreatic cancer chemopreventive agents may prove to be tremendously valuable for individuals at high risk of developing pancreatic cancer and patients who present with premalignant lesions. This Review discusses the current state of the pancreatic cancer chemoprevention field and highlights the challenges ahead.
Key Points
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Pancreatic cancer has a low survival rate, which has not improved in the past few decades; current chemotherapeutic treatment is not effective
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A great deal of research interest has been directed towards evaluating natural and synthetic chemopreventive agents in cellular and animal models of pancreatic cancer
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Few pancreatic cancer clinical trials with chemopreventive agents have been completed; more trials are in early phases
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Pancreatic cancer chemopreventive agents could be useful for individuals who are at high risk of developing cancer or who present with premalignant lesions
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Pancreatic cancer chemopreventive agents have a potential use as potentiators of standard chemotherapy
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References
Jemal, A. et al. Cancer statistics, 2009. CA Cancer J. Clin. 59, 225–249 (2009).
Ghadirian, P., Lynch, H. T. & Krewski, D. Epidemiology of pancreatic cancer: an overview. Cancer Detect. Prev. 27, 87–93 (2003).
Greer, J. B., Whitcomb, D. C. & Brand, R. E. Genetic predisposition to pancreatic cancer: a brief review. Am. J. Gastroenterol. 102, 2564–2569 (2007).
McKay, C. J., Glen, P. & McMillan, D. C. Chronic inflammation and pancreatic cancer. Best Pract. Res. Clin. Gastroenterol. 22, 65–73 (2008).
Ghaneh, P., Costello, E. & Neoptolemos, J. P. Biology and management of pancreatic cancer. Gut 56, 1134–1152 (2007).
Larsson, S. C., Hakanson, N., Permert, J. & Wolk, A. Meat, fish, poultry and egg consumption in relation to risk of pancreatic cancer: a prospective study. Int. J. Cancer 118, 2866–2870 (2006).
Nothlings, U. et al. Meat and fat intake as risk factors for pancreatic cancer: the multiethnic cohort study. J. Natl Cancer Inst. 97, 1458–1465 (2005).
Vrieling, A. et al. Fruit and vegetable consumption and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition. Int. J. Cancer 124, 1926–1934 (2009).
Wong, H. H. & Lemoine, N. R. Pancreatic cancer: molecular pathogenesis and new therapeutic targets. Nat. Rev. Gastroenterol. Hepatol. 6, 412–422 (2009).
Burris, H. A. 3rd et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J. Clin. Oncol. 15, 2403–2413 (1997).
Mancuso, A., Calabro, F. & Sternberg, C. N. Current therapies and advances in the treatment of pancreatic cancer. Crit. Rev. Oncol. Hematol. 58, 231–241 (2006).
Chua, Y. J. & Zalcberg, J. R. Pancreatic cancer—is the wall crumbling? Ann. Oncol. 19, 1224–1230 (2008).
Yu, X., Zhang, Y., Chen, C., Yao, Q. & Li, M. Targeted drug delivery in pancreatic cancer. Biochim. Biophys. Acta 1805, 97–104 (2010).
Bardeesy, N. & DePinho, R. A. Pancreatic cancer biology and genetics. Nat. Rev. Cancer 2, 897–909 (2002).
De La O, J. P. & Murtaugh, L. C. Notch and Kras in pancreatic cancer: at the crossroads of mutation, differentiation and signaling. Cell Cycle 8, 1860–1864 (2009).
Gidekel Friedlander, S. Y. et al. Context-dependent transformation of adult pancreatic cells by oncogenic K-Ras. Cancer Cell 16, 379–389 (2009).
Hruban, R. H. et al. K-ras oncogene activation in adenocarcinoma of the human pancreas. A study of 82 carcinomas using a combination of mutant-enriched polymerase chain reaction analysis and allele-specific oligonucleotide hybridization. Am. J. Pathol. 143, 545–554 (1993).
Moskaluk, C. A., Hruban, R. H. & Kern, S. E. p16 and K-ras gene mutations in the intraductal precursors of human pancreatic adenocarcinoma. Cancer Res. 57, 2140–2143 (1997).
Korc, M. et al. Overexpression of the epidermal growth factor receptor in human pancreatic cancer is associated with concomitant increases in the levels of epidermal growth factor and transforming growth factor alpha. J. Clin. Invest. 90, 1352–1369 (1992).
Ebert, M., Yokoyama, M., Friess, H., Büchler, M. W. & Korc, M. Coexpression of the c-met proto-oncogene and hepatocyte growth factor in human pancreatic cancer. Cancer Res. 54, 5775–5778 (1994).
Hakam, A., Fang, Q., Karl, R. & Coppola, D. Coexpression of IGF-1R and c-Src proteins in human pancreatic ductal adenocarcinoma. Dig. Dis. Sci. 48, 1972–1978 (2003).
Yamamoto, S. et al. Prognostic significance of activated Akt expression in pancreatic ductal adenocarcinoma. Clin. Cancer Res. 10, 2846–2850 (2004).
Scholz, A. et al. Activated signal transducer and activator of transcription 3 (STAT3) supports the malignant phenotype of human pancreatic cancer. Gastroenterology 125, 891–905 (2003).
Aggarwal, B. B. et al. Targeting signal-transducer-and-activator-of-transcription-3 for prevention and therapy of cancer: modern target but ancient solution. Ann. NY Acad. Sci. 1091, 151–169 (2006).
Hamacher, R., Schmid, R. M., Saur, D. & Schneider, G. Apoptotic pathways in pancreatic ductal adenocarcinoma. Mol. Cancer 7, 64 (2008).
Liptay, S. et al. Mitogenic and antiapoptotic role of constitutive NF-kB/Rel activity in pancreatic cancer. Int. J. Cancer 105, 735–746 (2003).
Fujioka, S. et al. Function of nuclear factor kB in pancreatic cancer metastasis. Clin. Cancer Res. 9, 346–354 (2003).
Greer, J. B. & Whitcomb, D. C. Inflammation and pancreatic cancer: an evidence-based review. Curr. Opin. Pharmacol. 9, 411–418 (2009).
Mysliwiec, P. & Boucher, M. J. Targeting Notch signaling in pancreatic cancer patients—rationale for new therapy. Adv. Med. Sci. 54, 136–142 (2009).
Hezel, A. F., Kimmelman, A. C., Stanger, B. Z., Bardeesy, N. & DePinho, R. A. Genetics and biology of pancreatic ductal adenocarcinoma. Genes Dev. 20, 1218–1249 (2006).
Goel, A., Kunnumakkara, A. B. & Aggarwal, B. B. Curcumin as “Curecumin”: from kitchen to clinic. Biochem. Pharmacol. 75, 787–809 (2008).
Reuter, S., Eifes, S., Dicato, M., Aggarwal, B. B. & Diederich, M. Modulation of anti-apoptotic and survival pathways by curcumin as a strategy to induce apoptosis in cancer cells. Biochem. Pharmacol. 76, 1340–1351 (2008).
Wang, W. et al. The nuclear factor-kB RelA transcription factor is constitutively activated in human pancreatic adenocarcinoma cells. Clin. Cancer Res. 5, 119–127 (1999).
Kunnumakkara, A. B. et al. Curcumin potentiates antitumor activity of gemcitabine in an orthotopic model of pancreatic cancer through suppression of proliferation, angiogenesis, and inhibition of nuclear factor-kappaB-regulated gene products. Cancer Res. 67, 3853–3861 (2007).
Lev-Ari, S. et al. Inhibition of pancreatic and lung adenocarcinoma cell survival by curcumin is associated with increased apoptosis, down-regulation of COX-2 and EGFR and inhibition of Erk1/2 activity. Anticancer Res. 26, 4423–4430 (2006).
Lev-Ari, S. et al. Curcumin augments gemcitabine cytotoxic effect on pancreatic adenocarcinoma cell lines. Cancer Invest. 25, 411–418 (2007).
Wang, Z., Zhang, Y., Banerjee, S., Li, Y. & Sarkar, F. H. Notch-1 down-regulation by curcumin is associated with the inhibition of cell growth and the induction of apoptosis in pancreatic cancer cells. Cancer 106, 2503–2513 (2006).
Sun, M. et al. Curcumin (diferuloylmethane) alters the expression profiles of microRNAs in human pancreatic cancer cells. Mol. Cancer Ther. 7, 464–473 (2008).
Lev-Ari, S. et al. Curcumin synergistically potentiates the growth inhibitory and pro-apoptotic effects of celecoxib in pancreatic adenocarcinoma cells. Biomed. Pharmacother. 59 (Suppl. 2), S276–S280 (2005).
Swamy, M. V. et al. Prevention and treatment of pancreatic cancer by curcumin in combination with omega-3 fatty acids. Nutr. Cancer 60 (Suppl. 1), 81–89 (2008).
Soni, K. & Kuttan, R. Effect of oral curcumin administration on serum peroxides and cholesterol levels in human volunteers. Indian J. Physiol. Pharmacol. 36, 273–275 (1992).
Sharma, R. A. et al. Phase I clinical trial of oral curcumin: biomarkers of systemic activity and compliance. Clin. Cancer Res. 10, 6847–6854 (2004).
Cheng, A. L. et al. Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high risk or pre-malignant lesions. Anticancer Res. 21, 2895–2900 (2001).
Friedman, L. et al. Curcumin analogues exhibit enhanced growth suppressive activity in human pancreatic cancer cells. Anticancer Drugs 20, 444–449 (2009).
Padhye, S. et al. New difluoro Knoevenagel condensates of curcumin, their Schiff bases and copper complexes as proteasome inhibitors and apoptosis inducers in cancer cells. Pharm. Res. 26, 1874–1880 (2009).
Li, L., Braiteh, F. S. & Kurzrock, R. Liposome-encapsulated curcumin: in vitro and in vivo effects on proliferation, apoptosis, signaling, and angiogenesis. Cancer 104, 1322–1331 (2005).
Dhillon, N. et al. Phase II trial of curcumin in patients with advanced pancreatic cancer. Clin. Cancer Res. 14, 4491–4499 (2008).
Ding, X. Z., Henning, R. & Adrian, T. E. Lipoxygenase and cyclooxygenase metabolism: new insights in treatment and chemoprevention of pancreatic cancer. Mol. Cancer 2, 10 (2003).
Tucker, O. N. et al. Cyclooxygenase-2 expression is up-regulated in human pancreatic cancer. Cancer Res. 59, 987–990 (1999).
Molina, M. A., Sitja-Arnau, M., Lemoine, M. G., Frazier, M. L. & Sinicrope, F. A. Increased cyclooxygenase-2 expression in human pancreatic carcinomas and cell lines: growth inhibition by nonsteroidal anti-inflammatory drugs. Cancer Res. 59, 4356–4362 (1999).
Kokawa, A. et al. Increased expression of cyclooxygenase-2 in human pancreatic neoplasms and potential for chemoprevention by cyclooxygenase inhibitors. Cancer 91, 333–338 (2001).
Wenger, F. A. et al. Effects of Celebrex and Zyflo on BOP-induced pancreatic cancer in Syrian hamsters. Pancreatology 2, 54–60 (2002).
Xu, X. F. et al. Selective inhibition of cyclooxygenase-2 suppresses the growth of pancreatic cancer cells in vitro and in vivo. Tohoku J. Exp. Med. 215, 149–157 (2008).
Wei, D. et al. Celecoxib inhibits vascular endothelial growth factor expression and reduces angiogenesis and metastasis of human pancreatic cancer via suppression of Sp1 transcription factor activity. Cancer Res. 64, 2030–2038 (2004).
Mukherjee, P. et al. Progression of pancreatic adenocarcinoma is significantly impeded with a combination of vaccine and COX-2 inhibition. J. Immunol. 182, 216–224 (2009).
Dragovich, T. et al. Gemcitabine plus celecoxib in patients with advanced or metastatic pancreatic adenocarcinoma: results of a phase II trial. Am. J. Clin. Oncol. 31, 157–162 (2008).
Phase III Trial of Gemcitabine, Curcumin and Celebrex in Patients with Advance or Inoperable Pancreatic Cancer. ClinicalTrials.gov [online], (2010).
Funahashi, H. et al. Delayed progression of pancreatic intraepithelial neoplasia in a conditional KrasG12D mouse model by a selective cyclooxygenase-2 inhibitor. Cancer Res. 67, 7068–7071 (2007).
Ding, X. Z., Tong, W. G. & Adrian, T. E. Blockade of cyclooxygenase-2 inhibits proliferation and induces apoptosis in human pancreatic cancer cells. Anticancer Res. 20, 2625–2631 (2000).
Takahashi, M. et al. Effects of various prostaglandin synthesis inhibitors on pancreatic carcinogenesis in hamsters after initiation with N-nitrosobis(2-oxopropyl)amine. Carcinogenesis 11, 393–395 (1990).
Anderson, K. E, Johnson, T. W., Lazovich, D. & Folsom, A. R. Association between nonsteroidal anti-inflammatory drug use and the incidence of pancreatic cancer. J. Natl Cancer Inst. 94, 1168–1171 (2002).
Schernhammer, E. S. et al. A prospective study of aspirin use and the risk of pancreatic cancer in women. J. Natl Cancer Inst. 96, 22–28 (2004).
Takada, M. et al. Suppression of human pancreatic carcinoma cell growth and invasion by epigallocatechin-3-gallate. Pancreas 25, 45–48 (2002).
Lyn-Cook, B. D. et al. Chemopreventive effects of tea extracts and various components on human pancreatic and prostate tumor cells in vitro. Nutr. Cancer 35, 80–86 (1999).
Takabayashi, F., Harada, N., Tahara, S., Kaneko, T. & Hara, Y. Effect of green tea catechins on the amount of 8-hydroxydeoxyguanosine (8-OHdG) in pancreatic and hepatic DNA after a single administration of N-nitrosobis(2-oxopropyl)amine (BOP). Pancreas 15, 109–112 (1997).
Majima, T., Tsutsumi, M., Nishino, H., Tsunoda, T. & Konishi, Y. Inhibitory effects of beta-carotene, palm carotene, and green tea polyphenols on pancreatic carcinogenesis initiated by N-nitrosobis(2-oxopropyl)amine in Syrian golden hamsters. Pancreas 16, 13–18 (1998).
Shibata, A., Mack, T. M., Paganini-Hill, A., Ross, R. K. & Henderson, B. E. A prospective study of pancreatic cancer in the elderly. Int. J. Cancer 58, 46–49 (1994).
Whittemore, A. S., Paffenbarger, R. S. Jr, Anderson, K. & Halpern, J. Early precursors of pancreatic cancer in college men. J. Chronic Dis. 36, 251–256 (1983).
Zatonski, W. A. et al. Cigarette smoking, alcohol, tea and coffee consumption and pancreas cancer risk: a case-control study from Opole, Poland. Int. J. Cancer 53, 601–607 (1993).
Ji, B. T. et al. Green tea consumption and the risk of pancreatic and colorectal cancers. Int. J. Cancer 70, 255–258 (1997).
Lin, Y. et al. Green tea consumption and the risk of pancreatic cancer in Japanese adults. Pancreas 37, 25–30 (2008).
Luo, J. et al. Green tea and coffee intake and risk of pancreatic cancer in a large-scale, population-based cohort study in Japan (JPHC study). Eur. J. Cancer Prev. 16, 542–548 (2007).
Harnack, L. J. et al. Smoking, alcohol, coffee, and tea intake and incidence of cancer of the exocrine pancreas: the Iowa Women's Health Study. Cancer Epidemiol. Biomarkers Prev. 6, 1081–1086 (1997).
Mack, T. M., Yu, M. C., Hanisch, R. & Henderson, B. E. Pancreas cancer and smoking, beverage consumption, and past medical history. J. Natl Cancer Inst. 76, 49–60 (1986).
Heilbrun, L. K., Nomura, A. & Stemmermann, G. N. Black tea consumption and cancer risk: a prospective study. Br. J. Cancer 54, 677–683 (1986).
Mizuno, S. et al. A multi-institute case–control study on the risk factors of developing pancreatic cancer. Jpn J. Clin. Oncol. 22, 286–291 (1992).
Chow, H.-H. S. et al. Phase I pharmacokinetic study of tea polyphenols following single-dose administration of epigallocatechin gallate and polyphenon E. Cancer Epidemiol. Biomarkers Prev. 10, 53–58 (2001).
Chow, H. H. et al. Pharmacokinetics and safety of green tea polyphenols after multiple-dose administration of epigallocatechin gallate and polyphenon E in healthy individuals. Clin. Cancer Res. 9, 3312–3319 (2003).
Appel, M. J., Roverts, G. & Woutersen, R. A. Inhibitory effects of micronutrients on pancreatic carcinogenesis in azaserine-treated rats. Carcinogenesis 12, 2157–2161 (1991).
Rautalahti, M. T. et al. The effects of supplementation with α-tocopherol and β-carotene on the incidence and mortality of carcinoma of the pancreas in a randomized, controlled trial. Cancer 86, 37–42 (1999).
Raut, C. P., McConkey, D. J. & Abbruzzese, J. L. in Cancer Chemoprevention, volume 2: Strategies for Cancer Chemoprevention (eds Kelloff, G. I., Hawk, E. T. & Sigman, C. C.) 489–499 (Humana Press Inc., Totowa, 2005).
Chiang, K. C. & Chen, T. C. Vitamin D for the prevention and treatment of pancreatic cancer. World J. Gastroenterol. 15, 3349–3354 (2009).
Kawa, S. et al. Vitamin D analogues up-regulate p21 and p27 during growth inhibition of pancreatic cancer cell lines. Br. J. Cancer 76, 884–889 (1997).
Colston, K. W., James, S. Y., Ofori-Kuragu, E. A., Binderup, L. & Grant, A. G. Vitamin D receptors and anti-proliferative effects of vitamin D derivatives in human pancreatic carcinoma cells in vivo and in vitro. Br. J. Cancer 76, 1017–1020 (1997).
Skinner, H. G. et al. Vitamin D intake and the risk for pancreatic cancer in two cohort studies. Cancer Epidemiol. Biomarkers Prev. 15, 1688–1695 (2006).
Stolzenberg-Solomon, R. Z. et al. A prospective nested case–control study of vitamin D status and pancreatic cancer risk in male smokers. Cancer Res. 66, 10213–10219 (2006).
Stolzenberg-Solomon, R. Z. et al. Serum vitamin D and risk of pancreatic cancer in the prostate, lung, colorectal, and ovarian screening trial. Cancer Res. 69, 1439–1447 (2009).
Evans, T. R. et al. A phase II trial of the vitamin D analogue Seocalcitol (EB1089) in patients with inoperable pancreatic cancer. Br. J. Cancer 86, 680–685 (2002).
Heisler, T., Towfigh, S., Simon, N., Liu, C. & McFadden, D. W. Peptide YY augments gross inhibition by vitamin E succinate of human pancreatic cancer cell growth. J. Surg. Res. 88, 23–25 (2000).
Ohlsson, B., Albrechtsson, E. & Axelson, J. Vitamins A and D but not E and K decreased the cell number in human pancreatic cancer cell lines. Scand. J. Gastroenterol. 39, 882–885 (2004).
Kelloff, G. J. et al. Clinical development plan: vitamin E. J. Cell. Biochem. Suppl. 20, 282–299 (1994).
Stolzenberg-Solomon, R. Z. et al. Vitamin E intake, α-tocopherol status, and pancreatic cancer in a cohort of male smokers. Am. J. Clin. Nutr. 89, 584–591 (2009).
Kelloff, G. J. et al. Farnesyl protein transferase inhibitors as potential cancer chemopreventives. Cancer Epidemiol. Biomarkers Prev. 6, 267–282 (1997).
Stark, M. J., Burke, Y. D., McKinzie, J. H., Ayoubi, A. S. & Crowell, P. L. Chemotherapy of pancreatic cancer with the monoterpene perillyl alcohol. Cancer Lett. 96, 15–21 (1995).
Stayrook, K. R., McKinzie, J. H., Burke, Y. D., Burke, Y. A. & Crowell, P. L. Induction of the apoptosis-promoting protein Bak by perillyl alcohol in pancreatic ductal adenocarcinoma relative to untransformed ductal epithelial cells. Carcinogenesis 18, 1655–1658 (1997).
Burke, Y. D., Stark, M. J., Roach, S. L., Sen, S. E. & Crowell, P. L. Inhibition of pancreatic cancer growth by the dietary isoprenoids farnesol and geraniol. Lipids 32, 151–156 (1997).
Wiseman, D. A., Werner, S. R. & Crowell, P. L. Cell cycle arrest by the isoprenoids perillyl alcohol, geraniol, and farnesol is mediated by p21Cip1 and p27Kip1 in human pancreatic adenocarcinoma cells. J. Pharmacol. Exp. Ther. 320, 1163–1170 (2007).
Matos, J. M. et al. A pilot study of perillyl alcohol in pancreatic cancer. J. Surg. Res. 147, 194–199 (2008).
Fahey, J. W., Zalcmann, A. T. & Talalay, P. The chemical diversity and distribution of glucosinolates and isothiocyanates among plants. Phytochemistry 56, 5–51 (2001).
Kallifatidis, G. et al. Sulforaphane targets pancreatic tumor-initiating cells by NF-kappaB-induced antiapoptotic signaling. Gut 58, 949–963 (2009).
Srivastava, S. K. & Singh, S. V. Cell cycle arrest, apoptosis induction and inhibition of nuclear factor kappa B activation in anti-proliferative activity of benzyl isothiocyanate against human pancreatic cancer cells. Carcinogenesis 25, 1701–1709 (2004).
Sahu, R. P., Zhang, R., Batra, S., Shi, Y. & Srivastava, S. K. Benzyl isothiocyanate-mediated generation of reactive oxygen species causes cell cycle arrest and induces apoptosis via activation of MAPK in human pancreatic cancer cells. Carcinogenesis 30, 1744–1753 (2009).
Basu, A. & Haldar, S. Anti-proliferative and proapoptotic effects of benzyl isothiocyanate on human pancreatic cancer cells is linked to death receptor activation and RasGAP/Rac1 down-modulation. Int. J. Oncol. 35, 593–599 (2009).
Son, H. Y. et al. Modifying effects of 4-phenylbuthyl isothiocyanate on N-nitrosobis(2-oxopropyl)amine-induced tumorigenesis in hamsters. Cancer Lett. 160, 141–147 (2000).
Nishikawa, A. et al. Chemopreventive effects of phenethyl isothiocyanate on lung and pancreatic tumorigenesis in N-nitrosobis(2-oxopropyl)amine-treated hamsters. Carcinogenesis 17, 1381–1384 (1996).
Li, Y. et al. Apoptosis-inducing effect of chemotherapeutic agents is potentiated by soy isoflavone genistein, a natural inhibitor of NF-kappaB in BxPC-3 pancreatic cancer cell line. Pancreas 28, e90–e95 (2004).
Wang, Z., Zhang, Y., Banerjee, S., Li, Y. & Sarker, F. H. Inhibition of nuclear factor kB activity by genistein is mediated via Notch-1 signaling pathway in pancreatic cancer cells. Int. J. Cancer 118, 1930–1936 (2006).
El-Rayes, B. E. et al. Potentiation of the effect of erlotinib by genistein in pancreatic cancer: the role of Akt and nuclear factor-kB. Cancer Res. 66, 10553–10559 (2006).
Ding, X. Z. & Adrian, T. E. Resveratrol inhibits proliferation and induces apoptosis in human pancreatic cancer cells. Pancreas 25, e71–e76 (2002).
Harikumar, K. B. et al. Resveratrol, a multitarget agent, can enhance antitumor activity of gemcitabine in vitro and in orthotopic mouse model of human pancreatic cancer. Int. J. Cancer doi:10.1002/ijc.25041.
Zhang, R., Humphreys, I., Sahu, R. P., Shi, Y. & Srivastava, S. K. In vitro and in vivo induction of apoptosis by capsaicin in pancreatic cancer cells is mediated through ROS generation and mitochondrial death pathway. Apoptosis 13, 1465–1478 (2008).
Azmi, A. S. et al. Chemoprevention of pancreatic cancer: characterization of Par-4 and its modulation by 3,3′ diindolylmethane (DIM). Pharm. Res. 25, 2117–2124 (2008).
Ali, S. et al. Apoptosis-inducing effect of erlotinib is potentiated by 3,3′-diindolylmethane in vitro and in vivo using an orthotopic model of pancreatic cancer. Mol. Cancer Ther. 7, 1708–1719 (2008).
Schneider, M. B. et al. Prevention of pancreatic cancer induction in hamsters by metformin. Gastroenterology 120, 1263–1270 (2001).
Kisfalvi, K., Eibl, G., Sinnett-Smith, J. & Rozengurt, E. Metformin disrupts crosstalk between G protein-coupled receptor and insulin receptor signaling systems and inhibits pancreatic cancer growth. Cancer Res. 69, 6539–6545 (2009).
Li, D., Yeung, S. C., Hassan, M. M., Konopleva, M. & Abbruzzese, J. L. Anti-diabetic therapies affect risk of pancreatic cancer. Gastroenterology 137, 482–488 (2009).
Ulrich, C. D. Pancreatic cancer in hereditary pancreatitis: consensus guidelines for prevention, screening and treatment. Pancreatology 1, 416–422 (2001).
Brand, R. E. et al. Advances in counseling and surveillance of patients at risk for pancreatic cancer. Gut 56, 1460–1469 (2006).
Acknowledgements
This work was supported in part by funds from Shirley Hobbs Martin Memorial Fund (awarded to R. E. Brand) and the National Cancer Institute grant R01CA101753 (awarded to S. V. Singh). We thank D. C. Whitcomb for helpful suggestions and feedback on the manuscript. We apologize to the investigators whose work could not be cited due to space limitations.
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Stan, S., Singh, S. & Brand, R. Chemoprevention strategies for pancreatic cancer. Nat Rev Gastroenterol Hepatol 7, 347–356 (2010). https://doi.org/10.1038/nrgastro.2010.61
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