Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–424.

Article  PubMed  Google Scholar 

Vogelstein B, Fearon ER, Hamilton SR, et al. Genetic alterations during colorectal-tumor development. N Engl J Med. 1988;319:525–32.

Article  CAS  PubMed  Google Scholar 

Leggett B, Whitehall V. Role of the serrated pathway in colorectal cancer pathogenesis. Gastroenterology. 2010;138:2088–100.

Article  CAS  PubMed  Google Scholar 

Snover DC. Update on the serrated pathway to colorectal carcinoma. Hum Pathol. 2011;42:1–10.

Article  PubMed  Google Scholar 

Sweetser S, Smyrk TC, Sinicrope FA. Serrated colon polyps as precursors to colorectal cancer. Clin Gastroenterol Hepatol. 2013;11:760–7.

Article  PubMed  Google Scholar 

Sugai T, Habano W, Takagi R, et al. Analysis of molecular alterations in laterally spreading tumors of the colorectum. J Gastroenterol. 2017;52:715–23.

Article  CAS  PubMed  Google Scholar 

Jass JR. Classification of colorectal cancer based on correlation of clinical, morphological and molecular features. Histopathology. 2007;50:113–30.

Article  CAS  PubMed  Google Scholar 

Pai RK, Mäkinen MJ M, Rosty C. Colorectal serrated lesions and polyps. In: WHO classification of tumours editorial board (Ed.) WHO classification of tumours of the digestive system IARC, Lyon. 2019 pp.163–9.

Kambara T. BRAF mutation is associated with DNA methylation in serrated polyps and cancers of the colorectum. Gut. 2004;53:1137–44.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Higuchi T, Sugihara K, Jass JR. Demographic and pathological characteristics of serrated polyps of colorectum. Histopathology. 2005;47:32–40.

Article  CAS  PubMed  Google Scholar 

O’Brien MJ, Yang S, Mack C, et al. Comparison of microsatellite instability, CpG Island methylation phenotype, BRAF and KRAS status in serrated polyps and traditional adenomas indicates separate pathways to distinct colorectal carcinoma end points. Am J Surg Pathol. 2006;30:1491–501.

Article  PubMed  Google Scholar 

Rosty C, Hewett DG, Brown IS, et al. Serrated polyps of the large intestine: current understanding of diagnosis, pathogenesis, and clinical management. J Gastroenterol. 2013;48:287–302.

Article  PubMed  Google Scholar 

Guinney J, Dienstmann R, Wang X, et al. The consensus molecular subtypes of colorectal cancer. Nat Med. 2015;21:1350–6.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Aderka D, Stintzing S, Heinemann V. Explaining the unexplainable: discrepancies in results from the CALGB/SWOG 80405 and FIRE-3 studies. Lancet Oncol. 2019;20:e274–83.

Article  PubMed  Google Scholar 

Lenz H-J, Ou F-S, Venook AP, et al. Impact of consensus molecular subtype on survival in patients with metastatic colorectal cancer: results from CALGB/SWOG 80405 (Alliance). J Clin Oncol. 2019;37:1876–85.

Article  PubMed  PubMed Central  Google Scholar 

Wallace K, Grau MV, Ahnen D, et al. The association of lifestyle and dietary factors with the risk for serrated polyps of the colorectum. Cancer Epidemiol Biomarkers Prev. 2009;18:2310–7.

Article  PubMed  PubMed Central  Google Scholar 

Jass JR, Whitehall VL, Young J, et al. Emerging concepts in colorectal neoplasia. Gastroenterology. 2002;123:862–76.

Article  CAS  PubMed  Google Scholar 

Lamb J. The connectivity map: using gene-expression signatures to connect small molecules, genes, and disease. Science. 2006;313:1929–35.

Article  CAS  PubMed  Google Scholar 

Jin L, Tu J, Jia J, et al. Drug-repurposing identified the combination of trolox C and cytisine for the treatment of type 2 diabetes. J Transl Med. 2014;12:153.

Article  PubMed  PubMed Central  Google Scholar 

Shigemizu D, Hu Z, Hung J-H, et al. Using functional signatures to identify repositioned drugs for breast, myelogenous leukemia and prostate cancer. PLoS Comput Biol. 2012;8: e1002347.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Musa A, Ghoraie LS, Zhang S-D, et al. A review of connectivity map and computational approaches in pharmacogenomics. Brief Bioinform. 2018;19:506–23.

CAS  PubMed  Google Scholar 

Sato T, Stange DE, Ferrante M, et al. Long-term expansion of epithelial organoids from human colon, adenoma, adenocarcinoma, and Barrett’s epithelium. Gastroenterology. 2011;141:1762–72.

Article  CAS  PubMed  Google Scholar 

Sugimoto S, Ohta Y, Fujii M, et al. Reconstruction of the human colon epithelium in vivo. Cell Stem Cell. 2018;22(171–6): e5.

Google Scholar 

Kagamu H, Kitano S, Yamaguchi O, et al. CD4(+) T-cell immunity in the peripheral blood correlates with response to anti-PD-1 therapy. Cancer Immunol Res. 2020;8:334–44.

Article  CAS  PubMed  Google Scholar 

Kosaka T, Nagamatsu G, Saito S, et al. Identification of drug candidate against prostate cancer from the aspect of somatic cell reprogramming. Cancer Sci. 2013;104:1017–26.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wada H, Sato Y, Fujimoto S, et al. Resveratrol inhibits development of colorectal adenoma via suppression of LEF1; comprehensive analysis with connectivity map. Cancer Sci. 2022;113:4374–84.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Takahashi S, Okamoto K, Tanahashi T, et al. S100P expression via DNA hypomethylation promotes cell growth in the sessile serrated adenoma/polyp-cancer sequence. Digestion. 2021;102:789–802.

Article  CAS  PubMed  Google Scholar 

Singh M, Dhindsa G, Friedland S, et al. Long-term use of proton pump inhibitors does not affect the frequency, growth, or histologic characteristics of colon adenomas. Aliment Pharmacol Ther. 2007;26:1051–61.

Article  CAS  PubMed  Google Scholar 

Johnson CC, Hayes RB, Schoen RE, et al. Non-steroidal anti-inflammatory drug use and colorectal polyps in the prostate, lung, colorectal, and ovarian cancer screening trial. Am J Gastroenterol. 2010;105:2646–55.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Carragher LA, Snell KR, Giblett SM, et al. V600EBraf induces gastrointestinal crypt senescence and promotes tumour progression through enhanced CpG methylation of p16INK4a. EMBO Mol Med. 2010;2:458–71.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sakamoto N, Feng Y, Stolfi C, et al. BRAF(V600E) cooperates with CDX2 inactivation to promote serrated colorectal tumorigenesis. Elife. 2017;6:e20331.

Article  PubMed  PubMed Central  Google Scholar 

Lannagan TRM, Lee YK, Wang T, et al. Genetic editing of colonic organoids provides a molecularly distinct and orthotopic preclinical model of serrated carcinogenesis. Gut. 2019;68:684–92.

Article  CAS  PubMed  Google Scholar 

Bond CE, Liu C, Kawamata F, et al. Oncogenic BRAF mutation induces DNA methylation changes in a murine model for human serrated colorectal neoplasia. Epigenetics. 2018;13:40–8.

Article  PubMed  PubMed Central  Google Scholar 

Shimokawa M, Ohta Y, Nishikori S, et al. Visualization and targeting of LGR5(+) human colon cancer stem cells. Nature. 2017;545:187–92.

Article  CAS  PubMed  Google Scholar 

Kikuchi H, Kato H, Mizuno M, et al. Differences in inducibility of CYP1A1-mRNA by benzimidazole compounds between human and mouse cells: evidences of a human-specific signal transduction pathway for CYP1A1 induction. Arch biochem biophys. 1996;334:235–40.

Article  CAS  PubMed  Google Scholar 

Hume S, Grou CP, Lascaux P, et al. The NUCKS1-SKP2-p21/p27 axis controls S phase entry. Nat Commun. 2021;12:6959.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Luciani F, Spada M, De Milito A, et al. Effect of proton pump inhibitor pretreatment on resistance of solid tumors to cytotoxic drugs. J Natl Cancer Inst. 2004;96:1702–13.

Article  CAS  PubMed  Google Scholar 

De Milito A, Canese R, Marino ML, et al. pH-dependent antitumor activity of proton pump inhibitors against human melanoma is mediated by inhibition of tumor acidity. Int J Cancer. 2010;127:207–19.

Article  PubMed  Google Scholar 

Patlolla JM, Zhang Y, Li Q, et al. Anti-carcinogenic properties of omeprazole against human colon cancer cells and azoxymethane-induced colonic aberrant crypt foci formation