1. Howlader N, Noone A, Krapcho M, Neyman N, Aminou R, Waldron W, Altekruse S, Kosary C, Ruhl J, Tatalovich Z, Cho H, Mariotto A, Eisner M, Lewis D, Chen H, Feuer E, Cronin K, Edwards B. SEER Cancer Statistics Review, 1975-2008, Bethesda, MD: national Cancer Institute. Based on November 200 SEER Data Submission, Posted to the SEER; 2011. Available from: [Last accessed on 2015 Jul 20].

2. Peery AF, Dellon ES, Lund J, Crockett SD, McGowan CE, Bulsiewicz WJ, Gangarosa LM, Thiny MT, Stizenberg K, Morgan DR, Ringel Y, Kim HP, Dibonaventura MD, Carroll CF, Allen JK, Cook SF, Sandler RS, Kappelman MD, Shaheen NJ. Burden of gastrointestinal disease in the United States: 2012 update. Gastroenterology 2012;143:1179-87e1-3.

3. Baron JA, Sandler RS, Bresalier RS, Quan H, Riddell R, Lanas A, Bolognese JA, Oxenius B, Horgan K, Loftus S, Morton DG. A randomized trial of rofecoxib for the chemoprevention of colorectal adenomas. Gastroenterology 2006;131:1674-82.

4. Bertagnolli MM, Eagle CJ, Zauber AG, Redston M, Solomon SD, Kim K, Tang J, Rosenstein RB, Wittes J, Corle D, Hess TM, Woloj GM, Boisserie F, Anderson WF, Viner JL, Bagheri D, Burn J, Chung DC, Dewar T, Foley TR, Hoffman N, Macrae F, Pruitt RE, Saltzman JR, Salzberg B, Sylwestrowicz T, Gordon GB, Hawk ET. Celecoxib for the prevention of sporadic colorectal adenomas. N Engl J Med 2006;355:873-84.

5. Helin-Salmivaara A, Saarelainen S, Gronroos JM, Vesalainen R, Klaukka T, Huupponen R. Risk of upper gastrointestinal events with the use of various NSAIDs: a case-control study in a general population. Scand J Gastroenterol 2007;42:923-32.

6. Kerr DJ, Dunn JA, Langman MJ, Smith JL, Midgley RS, Stanley A, Stokes JC, Julier P, Iveson C, Duvvuri R, McConkey CC. Rofecoxib and cardiovascular adverse events in adjuvant treatment of colorectal cancer. N Engl J Med 2007;357:360-9.

7. McGettigan P, Henry D. Cardiovascular risk and inhibition of cyclooxygenase: a systematic review of the observational studies of selective and nonselective inhibitors of cyclooxygenase 2. JAMA 2006;296:1633-44.

8. Modjtahedi H, Essapen S. Epidermal growth factor receptor inhibitors in cancer treatment: advances, challenges and opportunities. Anticancer Drugs 2009;20:851-5.

9. Overman MJ, Hoff PM. EGFR-targeted therapies in colorectal cancer. Dis Colon Rectum 2007;50:1259-70.

10. Venook AP. Epidermal growth factor receptor-targeted treatment for advanced colorectal carcinoma. Cancer 2005;103:2435-46.

11. Sipples R. Common side effects of anti-EGFR therapy: acneform rash. Semin Oncol Nurs 2006;22:28-34.

12. Gadaleta RM, van Mil SW, Oldenburg B, Siersema PD, Klomp LW, van Erpecum KJ. Bile acids and their nuclear receptor FXR: relevance for hepatobiliary and gastrointestinal disease. Biochim Biophys Acta 2010;1801:683-92.

13. Lee FY, Lee H, Hubbert ML, Edwards PA, Zhang Y. FXR, a multipurpose nuclear receptor. Trends Biochem Sci 2006;31:572-80.

14. Wang YD, Chen WD, Moore DD, Huang W. FXR: a metabolic regulator and cell protector. Cell Res 2008;18:1087-95.

15. Parks DJ, Blanchard SG, Bledsoe RK, Chandra G, Consler TG, Kliewer SA, Stimmel JB, Willson TM, Zavacki AM, Moore DD, Lehmann JM. Bile acids: natural ligands for an orphan nuclear receptor. Science 1999;284:1365-8.

16. Maloney PR, Parks DJ, Haffner CD, Fivush AM, Chandra G, Plunket KD, Creech KL, Moore LB, Wilson JG, Lewis MC, Jones SA, Willson TM. Identification of a chemical tool for the orphan nuclear receptor FXR. J Med Chem 2000;43:2971-4.

17. Pellicciari R, Fiorucci S, Camaioni E, Clerici C, Costantino G, Maloney PR, Morelli A, Parks DJ, Willson TM. 6alpha-ethyl-chenodeoxycholic acid (6-ECDCA), a potent and selective FXR agonist endowed with anticholestatic activity. J Med Chem 2002;45:3569-72.

18. Flatt B, Martin R, Wang TL, Mahaney P, Murphy B, Gu XH, Foster P, Li J, Pircher P, Petrowski M, Schulman I, Westin S, Wrobel J, Yan G, Bischoff E, Daige C, Mohan R. Discovery of XL335 (WAY-362450), a highly potent, selective, and orally active agonist of the farnesoid X receptor (FXR). J Med Chem 2009;52:904-7.

19. Fang S, Suh JM, Reilly SM, Yu E, Osborn O, Lackey D, Yoshihara E, Perino A, Jacinto S, Lukasheva Y, Atkins AR, Khvat A, Schnabl B, Yu RT, Brenner DA, Coulter S, Liddle C, Schoonjans K, Olefsky JM, Saltiel AR, Downes M, Evans RM. Intestinal FXR agonism promotes adipose tissue browning and reduces obesity and insulin resistance. Nat Med 2015;21:159-65.

20. Urizar NL, Liverman AB, Dodds DT, Silva FV, Ordentlich P, Yan Y, Gonzalez FJ, Heyman RA, Mangelsdorf DJ, Moore DD. A natural product that lowers cholesterol as an antagonist ligand for FXR. Science 2002;296:1703-6.

21. Dussault I, Beard R, Lin M, Hollister K, Chen J, Xiao JH, Chandraratna R, Forman BM. Identification of gene-selective modulators of the bile acid receptor FXR. J Biol Chem 2003;278:7027-33.

22. Bookout AL, Jeong Y, Downes M, Yu RT, Evans RM, Mangelsdorf DJ. Anatomical profiling of nuclear receptor expression reveals a hierarchical transcriptional network. Cell 2006;126:789-99.

23. Yang X, Downes M, Yu RT, Bookout AL, He W, Straume M, Mangelsdorf DJ, Evans RM. Nuclear receptor expression links the circadian clock to metabolism. Cell 2006;126:801-10.

24. Modica S, Gofflot F, Murzilli S, D'Orazio A, Salvatore L, Pellegrini F, Nicolucci A, Tognoni G, Copetti M, Valanzano R, Veschi S, Mariani-Costantini R, Palasciano G, Schoonjans K, Auwerx J, Moschetta A. The intestinal nuclear receptor signature with epithelial localization patterns and expression modulation in tumors. Gastroenterology 2010;138:636-48, 48e1-12.

25. Modica S, Cariello M, Morgano A, Gross I, Vegliante MC, Murzilli S, Salvatore L, Freund JN, Sabba C, Moschetta A. Transcriptional regulation of the intestinal nuclear bile acid farnesoid X receptor (FXR) by the caudal-related homeobox 2 (CDX2). J Biol Chem 2014;289:28421-32.

26. Bailey AM, Zhan L, Maru D, Shureiqi I, Pickering CR, Kiriakova G, Izzo J, He N, Wei C, Baladandayuthapani V, Liang H, Kopetz S, Powis G, Guo GL. FXR silencing in human colon cancer by DNA methylation and KRAS signaling. Am J Physiol Gastrointest Liver Physiol 2014;306:G48-58.

27. Cabrerizo R, Castano GO, Burgueno AL, Fernandez Gianotti T, Gonzalez Lopez Ledesma MM, Flichman D, Pirola CJ, Sookoian S. Promoter DNA methylation of farnesoid X receptor and pregnane X receptor modulates the intrahepatic cholestasis of pregnancy phenotype. PLoS One 2014;9:e87697.

28. Lou G, Li Y, Chen B, Chen M, Chen J, Liao R, Zhang Y, Wang Y, Zhou D. Functional analysis on the 5'-flanking region of human FXR gene in HepG2 cells. Gene 2007;396:358-68.

29. Modica S, Murzilli S, Salvatore L, Schmidt DR, Moschetta A. Nuclear bile acid receptor FXR protects against intestinal tumorigenesis. Cancer Res 2008;68:9589-94.

30. Maran RR, Thomas A, Roth M, Sheng Z, Esterly N, Pinson D, Gao X, Zhang Y, Ganapathy V, Gonzalez FJ, Guo GL. Farnesoid X receptor deficiency in mice leads to increased intestinal epithelial cell proliferation and tumor development. J Pharmacol Exp Ther 2009;328:469-77.

31. Smith DL, Keshavan P, Avissar U, Ahmed K, Zucker SD. Sodium taurocholate inhibits intestinal adenoma formation in APCMin/+ mice, potentially through activation of the farnesoid X receptor. Carcinogenesis 2010;31:1100-9.

32. De Gottardi A, Touri F, Maurer CA, Perez A, Maurhofer O, Ventre G, Bentzen CL, Niesor EJ, Dufour JF. The bile acid nuclear receptor FXR and the bile acid binding protein IBABP are differently expressed in colon cancer. Dig Dis Sci 2004;49:982-9.

33. Lax S, Schauer G, Prein K, Kapitan M, Silbert D, Berghold A, Berger A, Trauner M. Expression of the nuclear bile acid receptor/farnesoid X receptor is reduced in human colon carcinoma compared to nonneoplastic mucosa independent from site and may be associated with adverse prognosis. Int J Cancer 2012;130:2232-9.

34. Ullman TA, Itzkowitz SH. Intestinal inflammation and cancer. Gastroenterology 2011;140:1807-16.

35. Gadaleta RM, Cariello M, Sabba C, Moschetta A. Tissue-specific actions of FXR in metabolism and cancer. Biochim Biophys Acta 2015;1851:30-9.

36. Stojancevic M, Stankov K, Mikov M. The impact of farnesoid X receptor activation on intestinal permeability in inflammatory bowel disease. Can J Gastroenterol 2012;26:631-7.

37. Torres J, Bao X, Iuga AC, Chen A, Harpaz N, Ullman T, Cohen BL, Pineton de Chambrun G, Asciutti S, Odin JA, Sachar DB, Gaskins HR, Setchell K, Colombel JF, Itzkowitz SH. Farnesoid X receptor expression is decreased in colonic mucosa of patients with primary sclerosing cholangitis and colitis-associated neoplasia. Inflamm Bowel Dis 2013;19:275-82.

38. Peng Z, Raufman JP, Xie G. Src-mediated cross-talk between farnesoid X and epidermal growth factor receptors inhibits human intestinal cell proliferation and tumorigenesis. PLoS One 2012;7:e48461.

39. Yang F, Hu Y, Liu HX, Wan YJ. miR-22-silenced cyclin A expression in colon and liver cancer cells is regulated by bile acid receptor. J Biol Chem 2015;290:6507-15.

40. Gadaleta RM, Oldenburg B, Willemsen EC, Spit M, Murzilli S, Salvatore L, Klomp LW, Siersema PD, van Erpecum KJ, van Mil SW. Activation of bile salt nuclear receptor FXR is repressed by pro-inflammatory cytokines activating NF-kappaB signaling in the intestine. Biochim Biophys Acta 2011;1812:851-8.

41. Zhou X, Cao L, Jiang C, Xie Y, Cheng X, Krausz KW, Qi Y, Sun L, Shah YM, Gonzalez FJ, Wang G, Hao H. PPARalpha-UGT axis activation represses intestinal FXR-FGF15 feedback signalling and exacerbates experimental colitis. Nat Commun 2014;5:4573.

42. Berg A. Nutrition, development, and population growth. Popul Bull 1973;29:3-37.

43. Chao A, Thun MJ, Connell CJ, McCullough ML, Jacobs EJ, Flanders WD, Rodriguez C, Sinha R, Calle EE. Meat consumption and risk of colorectal cancer. JAMA 2005;293:172-82.

44. Kirkegaard H, Johnsen NF, Christensen J, Frederiksen K, Overvad K, Tjonneland A. Association of adherence to lifestyle recommendations and risk of colorectal cancer: a prospective Danish cohort study. BMJ 2010;341:c5504.

45. Bajor A, Gillberg PG, Abrahamsson H. Bile acids: short and long term effects in the intestine. Scand J Gastroenterol 2010;45:645-64.

46. McGarr SE, Ridlon JM, Hylemon PB. Diet, anaerobic bacterial metabolism, and colon cancer: a review of the literature. J Clin Gastroenterol 2005;39:98-109.

47. Bianchini F, Caderni G, Dolara P, Fantetti L, Kriebel D. Effect of dietary fat, starch and cellulose on fecal bile acids in mice. J Nutr 1989;119:1617-24.

48. Reddy BS, Hedges AR, Laakso K, Wynder EL. Metabolic epidemiology of large bowel cancer: fecal bulk and constituents of high-risk North American and low-risk Finnish population. Cancer 1978;42:2832-8.

49. Giovannucci E, Colditz GA, Stampfer MJ. A meta-analysis of cholecystectomy and risk of colorectal cancer. Gastroenterology 1993;105:130-41.

50. Lagergren J, Ye W, Ekbom A. Intestinal cancer after cholecystectomy: is bile involved in carcinogenesis? Gastroenterology 2001;121:542-7.

51. Degirolamo C, Modica S, Palasciano G, Moschetta A. Bile acids and colon cancer: solving the puzzle with nuclear receptors. Trends Mol Med 2011;17:564-72.

52. Cheng K, Chen Y, Zimniak P, Raufman JP, Xiao Y, Frucht H. Functional interaction of lithocholic acid conjugates with M3 muscarinic receptors on a human colon cancer cell line. Biochim Biophys Acta 2002;1588:48-55.

53. Cheng K, Raufman JP. Bile acid-induced proliferation of a human colon cancer cell line is mediated by transactivation of epidermal growth factor receptors. Biochem Pharmacol 2005;70:1035-47.

54. Raufman JP, Cheng K, Zimniak P. Activation of muscarinic receptor signaling by bile acids: physiological and medical implications. Dig Dis Sci 2003;48:1431-44.

55. Cheng K, Zimniak P, Raufman JP. Transactivation of the epidermal growth factor receptor mediates cholinergic agonist-induced proliferation of H508 human colon cancer cells. Cancer Res 2003;63:6744-50.

56. Degirolamo C, Modica S, Vacca M, Di Tullio G, Morgano A, D'Orazio A, Kannisto K, Parini P, Moschetta A. Prevention of spontaneous hepatocarcinogenesis in farnesoid X receptor-null mice by intestinal-specific farnesoid X receptor reactivation. Hepatology 2015;61:161-70.

57. Iannelli F, Collino A, Sinha S, Radaelli E, Nicoli P, D'Antiga L, Sonzogni A, Faivre J, Buendia MA, Sturm E, Thompson RJ, Knisely AS, Natoli G, Ghisletti S, Ciccarelli FD. Massive gene amplification drives paediatric hepatocellular carcinoma caused by bile salt export pump deficiency. Nat Commun 2014;5:3850.

58. Yang F, Huang X, Yi T, Yen Y, Moore DD, Huang W. Spontaneous development of liver tumors in the absence of the bile acid receptor farnesoid X receptor. Cancer Res 2007;67:863-7.

59. Schaap FG, Jansen PL, Olde Damink SW. FXR, intestinal FiXeR of hepatocellular carcinoma? Hepatology 2015;61:21-3.

60. Ma Y, Huang Y, Yan L, Gao M, Liu D. Synthetic FXR agonist GW4064 prevents diet-induced hepatic steatosis and insulin resistance. Pharm Res 2013;30:1447-57.

Journal of Cancer Metastasis and Treatment
ISSN 2454-2857 (Online) 2394-4722 (Print)


All published articles are preserved here permanently:


All published articles are preserved here permanently: