Advertisement

In Silico Studies on Colon Cancer

  • Sharad Singh Lodhi
  • Manish Sinha
  • Yogesh K. Jaiswal
  • Gulshan Wadhwa
Chapter

Abstract

The colon cancer (CC) is one of the most common malignancies, and more than one million people become the prey of colon cancer every year worldwide. The CC initiates, develops, and progresses in various ways. But all these ways cannot be understood fully to till date. So, any effort taken in the CC research is a step toward prevention and cure of this devastating disease. In the present scenario, there are various in silico approaches as well as computational strategies available for gene expression analysis for CC like SAGEmap, X Profiler, digital gene expression displayer (DGED), digital differential display (DDD), and Digital Extractor. The drug discovery and drug development are very cumbersome, intense, and interdisciplinary processes. There are various methods available for the in silico drug designing and development such as homology modeling, molecular docking, virtual high-throughput screening, quantitative structure-activity relationship, hologram quantitative structure-activity relationship (HQSAR), comparative molecular field analysis (CoMFA), comparative molecular similarity indices analysis (CoMSIA), pharmacophore mapping, microarray analysis, conformational analysis, and Monte Carlo simulation. With the help of in silico approaches, many novel drug targets for CC like cytochrome P450 2A7, Rab3A, SFRP1, TLR4, MLH1, MSH6, survivin, FGFR-4, and ras oncogene products (H-ras, K-ras, and N-ras) have been identified. Although these tools can act at good starting points in disease gene discovery, there is a need for experimental validation of in silico-derived differential expression and drug design results.

Keywords

Colon cancer Tumor suppressor gene In silico studies Gene expression 

References

  1. Anacleto C et al (2005) Colorectal cancer “methylator phenotype”: fact or artifact? Neoplasia 7(4):331–335CrossRefPubMedPubMedCentralGoogle Scholar
  2. Andreyev et al (2001) Kirsten ras mutations in patients with colorectal cancer: the ‘RASCAL II’ study. Br J Cancer 85(5):692–696Google Scholar
  3. Aqeilan RI et al (2010) miR-15a and miR-16-1 in cancer: discovery, function and future perspectives. Cell Death Differ 17(2):215–220CrossRefPubMedGoogle Scholar
  4. Baker SJ et al (1989) Chromosome 17 deletions and p53 gene mutations in colorectal carcinomas. Science 244:217–221CrossRefPubMedGoogle Scholar
  5. Berends MJW et al (2002) Molecular and clinical characteristics of MSH6 variants: an analysis of 25 index carriers of a germline variant. Am J Hum Genet 70(1):26–37CrossRefPubMedGoogle Scholar
  6. Bingham SA et al (2003) Dietary fibre in food and protection against colorectal cancer in the European prospective investigation into cancer and nutrition (EPIC): an observational study. Lancet 361:1496–1501CrossRefPubMedGoogle Scholar
  7. Bird RP (1987) Observation and quantification of aberrant crypts in the murine colon treated with a colon carcinogen: preliminary findings. Cancer Lett 37:147–151CrossRefPubMedGoogle Scholar
  8. Blobe GC et al (2000) Role of transforming growth factor beta in human disease. N Engl J Med 342:1350–135810CrossRefPubMedGoogle Scholar
  9. Cahill DP et al (1998) Mutations of mitotic checkpoint genes in human cancers. Nature 392:300–303CrossRefPubMedGoogle Scholar
  10. Cancer Genome Atlas Network (2012) Comprehensive molecular characterization of human colon and rectal cancer. Nature 487:330–337CrossRefGoogle Scholar
  11. Chapelle A (2004) Genetic predisposition to colorectal cancer. Nat Rev Cancer 4:769–780CrossRefPubMedGoogle Scholar
  12. Davies et al (2002) Mutations of the BRAF gene in human cancer. Nature 417(6892):949–954Google Scholar
  13. Delattre O et al (1989) Multiple genetic alterations in distal and proximal colorectal cancer. Lancet 334(8659):353–356CrossRefGoogle Scholar
  14. Douillard JY et al (2010) Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study. J Clin Oncol 28:4697–4705CrossRefPubMedGoogle Scholar
  15. Eppert K et al (1996) MADR2 maps to 18q21 and encodes a TGF beta-regulated MAD-related protein that is functionally mutated in colorectal carcinoma. Cell 86:543–552CrossRefPubMedGoogle Scholar
  16. Fearon ER, Vogelstein B (1990) A genetic model for colorectal tumorigenesis. Cell 61(5):759–767CrossRefGoogle Scholar
  17. Fleming NI et al (2013) SMAD2, SMAD3 and SMAD4 mutations in colorectal cancer. Cancer Res 73(2):725–735CrossRefPubMedGoogle Scholar
  18. Fodde R et al (2001) APC, signal transduction and genetic instability in colorectal cancer. Nat Rev Cancer 1(1):55–67CrossRefPubMedGoogle Scholar
  19. Forrester et al (1987) Detection of high incidence of K-ras oncogenes during human colon tumorigenesis. Nature 327:298–303CrossRefPubMedGoogle Scholar
  20. Gervaz P et al (2001) Dukes B colorectal cancer: distinct genetic categories and clinical outcome based on proximal or distal tumor location. Dis Colon Rectum 44(3):364–372CrossRefPubMedGoogle Scholar
  21. Giovannucci E, Martinez ME (1996) Tobacco, colorectal cancer, and adenomas: a review of the evidence. J Natl Cancer Inst 88:1717–1730CrossRefPubMedGoogle Scholar
  22. Groner B, Weiss A (2014) Targeting Survivin in cancer: novel drug development approaches. BioDrugs 28(1):27–39CrossRefPubMedGoogle Scholar
  23. Ho HK et al (2013) Developing FGFR4 inhibitors as potential anti-cancer agents via in silico design, supported by in vitro and cell-based testing. Curr Med Chem 20(10):1203–1217CrossRefPubMedGoogle Scholar
  24. Hurwitz H et al (2004) Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350:2335–2342CrossRefPubMedGoogle Scholar
  25. Ilyas M et al (1997) β-catenin mutations in cell lines established from human colorectal cancers. Proc Natl Acad Sci U S A 94:10330–10334CrossRefPubMedPubMedCentralGoogle Scholar
  26. Jallepalli PV, Lengauer C (2001) Chromosome segregation and cancer: cutting through the mystery. Nat Rev Cancer 1:109–117CrossRefPubMedGoogle Scholar
  27. Jemal A et al (2002) Cancer statistics. CA Cancer J Clin 52:23–47CrossRefPubMedGoogle Scholar
  28. Jongbum K, Sangsoo K (2014) In silico identification of SFRP1 as a Hypermethylated gene in colorectal cancers. Genomics Inform 12(4):171–180CrossRefGoogle Scholar
  29. Joy A et al (2014) MLH1 gene: an in silico analysis. J Comput Biol Bioinforma Res 5(1):1–5CrossRefGoogle Scholar
  30. Kinzler KW, Vogelstein B (1996) Lessons from hereditary colorectal cancer. Cell 87:159–170CrossRefPubMedGoogle Scholar
  31. Kobayashi H et al (2011) Characteristics of recurrence after curative resection for T1 colorectal cancer: Japanese multicenter study. J Gastroenterol 46(2):203–211CrossRefPubMedGoogle Scholar
  32. Labianca R et al (2000) Colon cancer. Crit Rev Oncol Hematol 51:145–170CrossRefGoogle Scholar
  33. Lamlum H et al (1999) The type of somatic mutation at APC in familial adenomatous polyposis is determined by the site of the germline mutation: a new facet to Knudson’s ‘two-hit’ hypothesis. Nat Med 5:1071–1075CrossRefPubMedGoogle Scholar
  34. Lammi L et al (2004) Mutations in AXIN2 cause familial tooth agenesis and predispose to colorectal cancer. Am J Hum Genet 74:1043–1050CrossRefPubMedPubMedCentralGoogle Scholar
  35. Li TT et al (2014) Toll-like receptor signaling in colorectal cancer: carcinogenesis to cancer therapy. World J Gastroenterol 20(47):17699–17708CrossRefPubMedPubMedCentralGoogle Scholar
  36. Lodhi SS et al (2012) Statistical analysis of differential gene expression profile for colon cancer. Indian J Biotechnol 11:396–403Google Scholar
  37. Lodhi SS et al (2014) 3D structure generation, virtual screening and docking of human Ras-associated binding (Rab3A) protein involved in tumourigenesis. Mol Biol Rep 41(6):3951–3959CrossRefPubMedGoogle Scholar
  38. Lodhi SS et al (2015) In silico structural, virtual screening and docking studies of human cytochrome P450 2A7 protein. Interdiscip Sci 7(2):129–135CrossRefPubMedGoogle Scholar
  39. Markowitz S et al (1995) Inactivation of the type II TGF-ß receptor in colon cancer cells with microsatellite instability. Science 268:1336–1338CrossRefPubMedGoogle Scholar
  40. Miyakura Y et al (2001) Extensive methylation of hMLH1 promoter region predominates in proximal colon cancer with microsatellite instability. Gastroenterology 121(6):1300–1309CrossRefPubMedGoogle Scholar
  41. Nagel R et al (2008) Regulation of the adeno- matous polyposis coli gene by the miR-135 family in colorectal cancer. Cancer Res 68:5795–5802CrossRefPubMedGoogle Scholar
  42. Nucci MR et al (1997) Phenotypic and genotypic characteristics of aberrant crypt foci in human colorectal mucosa. Hum Pathol 28:1396–1407CrossRefPubMedGoogle Scholar
  43. Papanikolaou A et al (1998) Azoxymethane-inducedcolon tumors and aberrant crypt foci in mice of different genetic susceptibility. Cancer Lett 14:29–34CrossRefGoogle Scholar
  44. Papanikolaou A et al (2000) Sequential and morphological analyses of aberrant crypt foci formation in mice of differingsusceptibility to azoxymethane-induced colon carcinogenesis. Carcinogenesis 21:1567–1572CrossRefPubMedGoogle Scholar
  45. Parsons DW et al (2005) Colorectal cancer: mutations in a signalling pathway. Nature 436:792CrossRefPubMedGoogle Scholar
  46. Rajagopalan H et al (2002) Tumorigenesis: RAF/RAS oncogenes and mismatch-repair status. Nature 418:934CrossRefGoogle Scholar
  47. Reya T, Clevers H (2005) Wnt signalling in stem cells and cancer. Nature 434:843–850CrossRefPubMedGoogle Scholar
  48. Rosenberg DW, Liu Y (1995) Induction of aberrant crypts in murine colon with varyingsensitivity to colon carcinogenesis. Cancer Lett 92:209–214CrossRefPubMedGoogle Scholar
  49. Samuels Y et al (2004) High frequency of mutations of the PIK3CA gene in human cancers. Science 304:554CrossRefPubMedGoogle Scholar
  50. Shima F et al (2013) In silico discovery of small-molecule Ras inhibitors that display antitumor activity by blocking the Ras-effector interaction. Proc Natl Acad Sci U S A 110(20):8182–8187CrossRefPubMedPubMedCentralGoogle Scholar
  51. Sparks AB et al (1998) Mutational analysis of the APC/β-catenin/Tcf pathway in colorectal cancer. Cancer Res 58:1130–1134PubMedGoogle Scholar
  52. Takayama T et al (2001) Analysis of K-ras, APC and β-catenin in aberrant crypt foci in patients with adenoma and cancer, and familial adenomatous polyposis. Gastroenterology 121:599–611CrossRefPubMedGoogle Scholar
  53. Thibodeau SN et al (1993) Microsatellite instability in cancer of the proximal colon. Science 260(5109):816–819CrossRefPubMedGoogle Scholar
  54. Tomatis L, Bartsch H (1990) The contribution of experimental studies to risk assessment of carcinogenic agents in humans. Exp Pathol 40:251–266CrossRefPubMedGoogle Scholar
  55. Van Cutsem E et al (2009) Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med 360:1408–1417CrossRefPubMedGoogle Scholar
  56. WCRF and AICR Food (1997) In: AIoC Research (ed) Nutrition and prevention of cancer: a global perspective. WCRF and AICR. World Cancer Research Fund and American Institute for Cancer Research, WashingtonGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  • Sharad Singh Lodhi
    • 1
  • Manish Sinha
    • 2
  • Yogesh K. Jaiswal
    • 1
  • Gulshan Wadhwa
    • 3
  1. 1.School of Studies in BiochemistryJiwaji UniversityGwaliorIndia
  2. 2.Laureate Institute of PharmacyKangraIndia
  3. 3.Department of Biotechnology, Apex Bioinformatics CentreMinistry of Science & TechnologyNew DelhiIndia

Personalised recommendations