Skip to main content

Advertisement

SpringerLink
Log in

Molecular biology as a tool for the treatment of cancer

  • Review Article
  • Published:
Clinical and Experimental Medicine Aims and scope Submit manuscript

Abstract

Cancer is a genetic disease characterized by uncontrolled cell growth and metastasis. Cancer can have a number of causes, such the activation of oncogenes, the inactivation of tumor-suppressing genes, mutagenesis provoked by external factors, and epigenetic modifications. The development of diagnostic tools and treatments using a molecular biological approach permits the use of sensitive, low-cost, noninvasive tests for cancer patients. Biomarkers can be used to provide rapid, personalized oncology, in particular the molecular diagnosis of chronic myeloid leukemia, and gastric, colon, and breast cancers. Molecular tests based on DNA methylation can also be used to direct treatments or evaluate the toxic effects of chemotherapy. The adequate diagnosis, prognosis, and prediction of the response of cancer patients to treatment are essential to ensure the most effective therapy, reduce the damaging effects of treatment, and direct the therapy to specific targets, and in this context, molecular biology has become increasingly important in oncology. In this brief review, we will demonstrate the fundamental importance of molecular biology for the treatment of three types of cancer—chronic myeloid leukemia, hereditary diffuse gastric cancer, and astrocytomas (sporadic tumors of the central nervous system). In each of these three models, distinct biological mechanisms are involved in the transformation of the cells, but in all cases, molecular biology is fundamental to the development of personalized analyses for each patient and each type of neoplasia, and to guarantee the success of the treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Knudson AG. Overview. Genes that predispose to cancer. Mutat Res. 1991;247:185–90.

    PubMed  Google Scholar 

  2. Martincorena I, Campbell PJ. Somatic mutation in cancer and normal cells. Science. 2016;351(6277):1483–8.

    Google Scholar 

  3. Vogelstein B, Kinzler KW. The multistep nature of cancer. Trends Genet. 1993;9:138–41.

    CAS  PubMed  Google Scholar 

  4. Von Hansemann D. Ueber asymmetrische Zelltheilung in Epithelhresbsen und deren biologische bedeutung. Virchows Arch A Pathol Anat. 1890;119:299–326.

    Google Scholar 

  5. Boveri T. Zur Frage der Entstehung maligner Tumoren. Jena: Publisher G Fischer; 1914. p. 64.

    Google Scholar 

  6. Manchester KL. Theodor Boveri and the origin of malignant tumours. Trends Cell Biol. 1995;5(10):384–7.

    CAS  PubMed  Google Scholar 

  7. Nowell P, Hungerford D. A minute chromosome in human chronic granulocytic leukemia. Science. 1960;132:1497.

    Google Scholar 

  8. Baltzer F. Theodor Boveri. Science. 1964;144:809–15.

    CAS  PubMed  Google Scholar 

  9. Lander ES, International Human Genome Sequencing Consortium, et al. Initial sequencing and analysis of the human genome. Nature. 2001;409:860–921.

    CAS  PubMed  Google Scholar 

  10. Venter JC, Adams MD, Myers EW, et al. The sequence of the human genome. Science. 2001;291:1304–51.

    CAS  PubMed  Google Scholar 

  11. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646–74.

    CAS  PubMed  Google Scholar 

  12. Loeb KR, Loeb LA. Significance of multiple mutations in cancer. Carcinogenesis. 2000;21(3):379–85.

    CAS  PubMed  Google Scholar 

  13. Barak V, Meirovitz A, Leibovici V, et al. The diagnostic and prognostic value of tumor markers (CEA, SCC, CYFRA 21-1, TPS) in head and neck cancer patients. Anticancer Res. 2015;35(10):5519–24.

    CAS  PubMed  Google Scholar 

  14. Kazarian A, Blyuss O, Metodieva G, et al. Testing breast cancer serum biomarkers for early detection and prognosis in pre-diagnosis samples. Br J Cancer. 2017;116(4):501–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Chistiakov DA, Myasoedova VA, Grechko AV, Melnichenko AA, Orekhov AN. New biomarkers for diagnosis and prognosis of localized prostate cancer. Semin Cancer Biol. 2018;17:30288-2.

    Google Scholar 

  16. Witte ON. Role of the BCR-ABL oncogene in human leukemia: fifteenth Richard and Hinda Rosenthal Foundation Award Lecture. Cancer Res. 1993;53:485–9.

    CAS  PubMed  Google Scholar 

  17. Grossmann V, Kohlmann A, Zenger M, et al. A deep-sequencing study of chronic myeloid leukemia patients in blast crisis (BC-CML) detects mutations in 76.9% of cases. Leukemia. 2011;25:557–61.

    CAS  PubMed  Google Scholar 

  18. Branford S. Monitoring after successful therapy for chronic myeloid leukemia. Hematology Am Soc Hematol Educ Program. 2012;2012:105–10.

    PubMed  Google Scholar 

  19. Hantschel O, Grebien F, Superti-Furga G. The growing arsenal of ATP-competitive and allosteric inhibitors of BCR-ABL. Cancer Res. 2012;72:4890–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Holyoake TL, Vetrie D. The chronic myeloid leukemia stem cell: stemming the tide of persistence. Blood. 2017;129:1595–606.

    CAS  PubMed  Google Scholar 

  21. Kujak C, Kolesar JM. Treatment of chronic myelogenous leukemia. Am J Health Syst Pharm. 2016;73:113–20.

    CAS  PubMed  Google Scholar 

  22. Baccarani M, Deininger M, Rosti G, et al. European LeukemiaNet recommendations for the management of chronic myeloid leukemia. Blood. 2013;122:872–84.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Morotti A, Fava C, Saglio G. Milestones and Monitoring. Curr Hematol Malig Rep. 2015;10:167–72.

    PubMed  PubMed Central  Google Scholar 

  24. NCCN. Clinical practice guidelines in oncology: chronic myelogenous leukemia. Version 1. 2016. http://www.nccn.org. Accessed 19 June 2018.

  25. Goldman JM. Chronic myeloid leukemia: a historical perspective. Semin Hematol. 2010;47:302–11.

    CAS  PubMed  Google Scholar 

  26. Goldman JM, Melo JV. Chronic myeloid leukemia—advances in biology and new approaches to treatment. New Engl J Med. 2003;349:1451–64.

    CAS  PubMed  Google Scholar 

  27. Marum JE, Branford S. Current developments in molecular monitoring in chronic myeloid leukemia. Ther Adv Hematol. 2016;7:237–51.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Deininger MW. Molecular monitoring in CML and the prospects for treatment-free remissions. Hematol Am Soc Hematol Educ Progr. 2015;2015:257–63.

    Google Scholar 

  29. Jabbour E, Kantarjian HM, Saglio G, et al. Early response with dasatinib or imatinib in chronic myeloid leukemia: 3-year follow-up from a randomized phase 3 trial (DASISION). Blood. 2014;123:494–500.

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Hanfstein B, Muller MC, Hehlmann R, et al. Early molecular and cytogenetic response is predictive for long-term progression-free and overall survival in chronic myeloid leukemia (CML). Leukemia. 2012;26:2096–102.

    CAS  PubMed  Google Scholar 

  31. Hughes T, Deininger M, Hochhaus A, et al. Monitoring CML patients responding to treatment with tyrosine kinase inhibitors: review and recommendations for harmonizing current methodology for detecting BCR-ABL transcripts and kinase domain mutations and for expressing results. Blood. 2006;108:28–37.

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Muller MC, Saglio G, Lin F, et al. An international study to standardize the detection and quantitation of BCR-ABL transcripts from stabilized peripheral blood preparations by quantitative RT-PCR. Haematologica. 2007;92:970–3.

    PubMed  Google Scholar 

  33. Cross NC, White HE, Muller MC, Saglio G, Hochhaus A. Standardized definitions of molecular response in chronic myeloid leukemia. Leukemia. 2012;26:2172–5.

    CAS  PubMed  Google Scholar 

  34. Mahon FX, Rea D, Guilhot J, et al. Discontinuation of imatinib in patients with chronic myeloid leukaemia who have maintained complete molecular remission for at least 2 years: the prospective, multicentre Stop Imatinib (STIM) trial. Lancet Oncol. 2010;11:1029–35.

    CAS  PubMed  Google Scholar 

  35. Ross DM, Branford S, Seymour JF, et al. Safety and efficacy of imatinib cessation for CML patients with stable undetectable minimal residual disease: results from the TWISTER study. Blood. 2013;122:515–22.

    CAS  PubMed  Google Scholar 

  36. Rousselot P, Charbonnier A, Cony-Makhoul P, et al. Loss of major molecular response as a trigger for restarting tyrosine kinase inhibitor therapy in patients with chronic-phase chronic myelogenous leukemia who have stopped imatinib after durable undetectable disease. J Clin Oncol Off J Am Soc Clin Oncol. 2014;32:424–30.

    CAS  Google Scholar 

  37. Sweet K, Zhang L, Pinilla-Ibarz J. Biomarkers for determining the prognosis in chronic myelogenous leukemia. J Hematol Oncol. 2013;6(54):1–9.

    Google Scholar 

  38. Weisberg E, Manley PW, Breitenstein W, et al. Characterization of AMN107, a selective inhibitor of native and mutant Bcr-Abl. Cancer Cell. 2005;7:129–41.

    CAS  PubMed  Google Scholar 

  39. Lopes NR, Abreu MTCL. Inibidores de tirosino quinase na leucemia mieloide crônica. Rev Bras Hematol Hemoter. 2009;31:449–53.

    Google Scholar 

  40. Gruber FX, Ernst T, Porkka K, et al. Dynamics of the emergence of dasatinib and nilotinib resistance in imatinib-resistante CML patients. Leukemia. 2012;26(1):172–7.

    CAS  PubMed  Google Scholar 

  41. Saglio G, Fava C. BCR-ABL1 mutation not equal ponatinib resistance. Blood. 2016;127(6):666–7.

    CAS  PubMed  Google Scholar 

  42. Lei H, Jin J, Liu M, et al. Chk1 inhibitors overcome imatinib resistance in chronic myeloid leukemia cells. Leuk Res. 2018;64:17–23.

    CAS  PubMed  Google Scholar 

  43. Golas JM, Arndt K, Etienne C, et al. SKI-606, a 4-anilino-3-quinolinecarbonitrile dual inhibitor of Src and Abl kinases, is a potent antiproliferative agent against chronic myelogenous leukemia cells in culture and causes regression of K562 xenografts in nude mice. Cancer Res. 2003;63:375–81.

    CAS  PubMed  Google Scholar 

  44. Remsing Rix LL, Rix U, Colinge J, et al. Global target profile of the kinase inhibitor bosutinib in primary chronic myeloid leukemia cells. Leukemia. 2009;23:477–85.

    CAS  PubMed  Google Scholar 

  45. Gambacorti-Passerini C, Brummendorf TH, Kim DW, et al. Bosutinib efficacy and safety in chronic phase chronic myeloid leukemia after imatinib resistance or intolerance: minimum 24-month follow-up. Am J Hematol. 2014;89:732–42.

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Isfort S, Brümmendorf TH. Bosutinib in chronic myeloid leukemia: patient selection and perspectives. J Blood Med. 2018;9:43–50.

    PubMed  PubMed Central  Google Scholar 

  47. Müller MC, Cervantes F, Hjorth-Hansen H, Janssen JJWM, Milojkovic D, Rea D, Rosti G. Ponatinib in chronic myeloid leukemia (CML): consensus on patient treatment and management from a European expert panel. Crit Rev Oncol Hematol. 2017;120:52–9.

    PubMed  Google Scholar 

  48. O’Hare T, Shakespeare WC, Zhu X, et al. AP24534, a pan-BCR-ABL inhibitor for chronic myeloid leukemia, potently inhibits the T315I mutant and overcomes mutation-based resistance. Cancer Cell. 2009;16:401–12.

    PubMed  PubMed Central  Google Scholar 

  49. Cortes JE, Kim DW, Pinilla-Ibarz J. A phase 2 trial of ponatinib in Philadelphia chromosome-positive leukemias. New Engl J Med. 2013;369:1783–96.

    CAS  PubMed  Google Scholar 

  50. Corbin AS, Agarwal A, Loriaux M, Cortes J, Deininger MW, Druker BJ. Human chronic myeloid leukemia stem cells are insensitive to imatinib despite inhibition of BCR-ABL activity. J Clin Investig. 2011;121(1):396–409.

    CAS  PubMed  Google Scholar 

  51. Rousselot P, Huguet F, Rea D, Legros L, Cayuela JM, Maarek O, et al. Imatinib mesylate discontinuation in patients with chronic myelogenous leukemia in complete molecular remission for more than 2 years. Blood. 2007;109(1):58–60.

    CAS  PubMed  Google Scholar 

  52. Shah NP, Kantarjian HM, Kim DW, Réa D, DorlhiacLlacer PE, Milone JH, et al. Intermittent target inhibition with dasatinib 100 mg once daily preserves efficacy and improves tolerability in imatinib-resistant and -intolerant chronic-phase chronic myeloid leukemia. J Clin Oncol. 2008;26(19):3204–12.

    CAS  PubMed  Google Scholar 

  53. Rea D, Nicolini FE, Tulliez M, et al. Discontinuation of dasatinib or nilotinib in chronic myeloid leukemia: interim analysis of the STOP 2G-TKI study. Blood. 2017;129:846–54.

    CAS  PubMed  Google Scholar 

  54. Legros L, Nicolini FE, Etienne G, et al. Second tyrosine kinase inhibitor discontinuation attempt in patients with chronic myeloid leukemia. Cancer. 2017;123:4403–10.

    CAS  PubMed  Google Scholar 

  55. Rea D, Cavuela JM. Treatment-free remission in patients with chronic myeloid leukemia. Int J Hematol 2017. https://doi.org/10.1007/s12185-017-2295-0

    Article  PubMed  Google Scholar 

  56. Laneuville P. Stopping second-generation TKIs in CML. Blood. 2017;129(7):805–6.

    CAS  PubMed  Google Scholar 

  57. Lee SE, Choi SY, Song HY, Kim SH, Choi MY, Park JS, et al. Imatinib withdrawal syndrome and longer duration of imatinib have a close association with a lower molecular relapse after 3 treatment discontinuation: the KID study. Haematologica. 2016;101(6):717–23.

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Soverini S, Hochhaus A, Nicolini FE, et al. BCR-ABL kinase domain mutation analysis in chronic myeloid leukemia patients treated with tyrosine kinase inhibitors: recommendations from an expert panel on behalf of European LeukemiaNet. Blood. 2011;118(5):1208–15.

    CAS  PubMed  Google Scholar 

  59. Apperley JF. Part I: mechanisms of resistance to imatinib in chronic myeloid leukaemia. Lancet Oncol. 2007;8:1018–29.

    CAS  PubMed  Google Scholar 

  60. Liu X, Kung A, Malinoski B, Prakash GK, Zhang C. Development of alkyne-containing pyrazolopyrimidines to overcome drug resistance of Bcr-Abl kinase. J Med Chem. 2015;58(23):9228–37.

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Jabbour E, Kantarjian H. Chronic myeloid leukemia: 2016 update on diagnosis, therapy, and monitoring. Am J Hematol. 2016;91(2):252–65.

    CAS  PubMed  Google Scholar 

  62. Cheetham GM, Charlton PA, Golec JM, Pollard JR. Structural basis for potent inhibition of the Aurora kinases and a T315I multi-drug resistant mutant form of Abl kinase by VX-680. Cancer Lett. 2007;251:323–9.

    CAS  PubMed  Google Scholar 

  63. Pollard JR, Mortimore M. Discovery and development of aurora kinase inhibitors as anticancer agents. J Med Chem. 2009;52:2629–51.

    CAS  PubMed  Google Scholar 

  64. Seymour JF, Kim DW, Rubin E, et al. A phase 2 study of MK-0457 in patients with BCR-ABL T315I mutant chronic myelogenous leukemia and philadelphia chromosome-positive acute lymphoblastic leukemia. Blood Cancer J. 2014;4(e238):1–6.

    Google Scholar 

  65. Yan M, Wang C, He B, et al. Aurora-A kinase: a potent oncogene and target for cancer therapy. Med Res Rev. 2016;36:1036–79.

    PubMed  Google Scholar 

  66. Afonso O, Figueiredo AC, Maiato H. Late mitotic functions of Aurora kinases. Chromosoma. 2017;126:93–103.

    CAS  PubMed  Google Scholar 

  67. Carter TA, Wodicka LM, Shah NP, et al. Inhibition of drug-resistant mutants of ABL, KIT, and EGF receptor kinases. Proc Natl Acad Sci USA. 2005;102(31):11011–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Giles FJ, Cortes J, Jones D, Bergstrom D, Kantarjian H, Freedman SJ. MK-0457, a novel kinase inhibitor, is active in patients with chronic myeloid leukemia or acute lymphocytic leukemia with the T315I BCR-ABL mutation. Blood. 2007;109(2):500–2.

    CAS  PubMed  Google Scholar 

  69. Akahane D, Tauchi T, Okabe S, Nunoda K, Ohyashiki K. Activity of a novel Aurora kinase inhibitor against the T315I mutant form of BCR-ABL: in vitro and in vivo studies. Cancer Sci. 2008;99:1251–7.

    CAS  PubMed  Google Scholar 

  70. Yaghoobi M, Rakhshani N, Sadr F, et al. Hereditary risk factors for the development of gastric cancer in younger patients. BMC Gastroenterol. 2004;4(28):1–7.

    Google Scholar 

  71. Antoniou AC, Casadei S, Heikkinen T, et al. Breast-cancer risk in families with mutations in PALB2. New Engl J Med. 2014;371:497–506.

    PubMed  Google Scholar 

  72. Imyanitov EN, Moiseyenko VM. Drug therapy for hereditary cancers. Hered Cancer Clin Pract. 2011;9:1–16.

    Google Scholar 

  73. Dantas ELR, Sá FHL, Carvalho SMF, Arruda AP, Ribeiro EM, Ribeiro EM. Genética do Câncer Hereditário. Rev Bras de Cancerol. 2009;55:263–9.

    Google Scholar 

  74. Howlader N, Noone AM, Krapcho M, Miller D, Bishop K, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). SEER cancer statistics review, 1975–2013. National Cancer Institute. Bethesda, MD, https://seer.cancer.gov/csr/1975_2013/, based on November 2015 SEER data submission, posted to the SEER web site, April 2016. Accessed 10 Mar 2018.

  75. Guilford P, Hopkins J, Harraway J, et al. E-cadherin germline mutations in familial gastric cancer. Nature. 1998;392:402–5.

    CAS  PubMed  Google Scholar 

  76. Dunbier A, Guilford P. Hereditary diffuse gastric cancer. Adv Cancer Res. 2001;83:55–65.

    CAS  PubMed  Google Scholar 

  77. Moran CJ, Joyce M, McAnena OJ. CDH1 associated gastric cancer: a report of a family and review of the literature. EJSO. 2005;31:259–64.

    CAS  PubMed  Google Scholar 

  78. Hansford S, Kaurah P, Li-Chang H, et al. Hereditary diffuse gastric cancer syndrome: CDH1 mutations and beyond. JAMA Oncol. 2015;1(1):23–32.

    PubMed  Google Scholar 

  79. Feroce I, Serrano D, Biffi R, et al. Hereditary diffuse gastric cancer in two families: a case report. Oncol Lett. 2017;14:1671–4.

    PubMed  PubMed Central  Google Scholar 

  80. Oliveira C, Suriano G, Ferreira P, et al. Genetic screening for familial gastric cancer. Hered Cancer Clin Pract. 2004;2:51–64.

    CAS  PubMed  PubMed Central  Google Scholar 

  81. Assumpção PP, Burbano, RR Genética Do Câncer Gástrico In: Linhares E, Lourenço, Sano T (eds) Atualização em Câncer Gástrico. Tecmedd: Ribeirão Preto; 2005. pp. 95-108

  82. Caldas C, Carneiro F, Lynch HT, et al. Familial gastric cancer: overview and guidelines for management. J Med Genet. 1999;36:873–80.

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Fitzgerald RC, Hardwick R, Huntsman D, et al. Hereditary diffuse gastric cancer: updated consensus guidelines for clinical management and directions for future research. J Med Genet. 2010;47:436–44.

    CAS  PubMed  Google Scholar 

  84. Gumbiner B, Stevenson B, Grimaldi A. The role of the cell adhesion molecule uvomorulin in the formation and maintenance of the epithelial junctional complex. J Cell Biol. 1988;107:1575–87.

    CAS  PubMed  Google Scholar 

  85. Green KJ, Getsios S, Troyanovsky S, Godsel LM. Intercellular junction assembly, dynamics, and homeostasis. Cold Spring Harb Perspect Biol. 2010;2(2):1–22.

    Google Scholar 

  86. Mateus AR, Simões-Correia J, Figueiredo J, et al. E-cadherin mutations and cell motility: a genotype–phenotype correlation. Exp Cell Res. 2009;315:1393–402.

    CAS  PubMed  Google Scholar 

  87. Ghaffari SR, Rafati M, Sabokbar T, Dastan J. A novel truncating mutation in the E-cadherin gene in the first Iranian family with hereditary diffuse gastric cancer. EJSO. 2010;36:559–62.

    CAS  PubMed  Google Scholar 

  88. Mayrbaeurla B, Kellerf G, Schauerb W, et al. Germline mutation of the E-cadherin gene in three sibling cases with advanced gastric cancer: clinical consequences for the other family members. Eur J Gastroenterol Hepatol. 2010;22:306–10.

    Google Scholar 

  89. Van der Post RS, Vogelaar IP, Carneiro F, et al. Hereditary diffuse gastric cancer: updated clinical guidelines with an emphasis on germline CDH1 mutation carriers. J Med Genet. 2015;52(6):361–74.

    PubMed  Google Scholar 

  90. Zylberberg HM, Sultan K, Rubin S. Hereditary diffuse gastric cancer: one family’s story. World J Clin Cases. 2018;6(1):1–5.

    PubMed  PubMed Central  Google Scholar 

  91. Knudson AG Jr. Prince Takamatsu memorial lecture. Rare cancers: clues to genetic mechanisms. Princess Takamatsu Symp. 1987;18:221–31.

    PubMed  Google Scholar 

  92. Chen LC, Kurisu W, Ljung BM, Goldman ES, Moore D 2nd, Smith HS. Heterogeneity for allelic loss in human breast cancer. J Natl Cancer Inst. 1992;84:506–10.

    CAS  PubMed  Google Scholar 

  93. Oliveira C, Pinheiro H, Figueiredo J, Seruca R, Carneiro F. Familial gastric cancer: genetic susceptibility, pathology, and implications for management. Lancet Oncol. 2015;16:e60–70.

    PubMed  Google Scholar 

  94. Corso G, Marrelli D, Pascale V, Vindigni C, Roviello F. Frequency of CDH1 germline mutations in gastric carcinoma coming from high- and low-risk areas: metanalysis and systematic review of the literature. BMC Cancer. 2012;12(8):1–10.

    Google Scholar 

  95. Fitzgerald RC, Caldas C. E-cadherin mutations and hereditary gastric cancer: prevention by resection? Dig Dis. 2002;20:23–31.

    CAS  PubMed  Google Scholar 

  96. Guilford P, Humar B, Blair V. Hereditary diffuse gastric cancer: translation of CDH1 germline mutations into clinical practice. Gastric Cancer. 2010;13:1–10.

    CAS  PubMed  Google Scholar 

  97. Corso G, Roviello F, Paredes J, et al. Characterization of the P373L E-cadherin germline missense mutation and implication for clinical management. EJSO. 2007;33:1061–7.

    CAS  PubMed  Google Scholar 

  98. Shinmura K, Kohno T, Takahashi M, et al. Familial gastric cancer: clinicopathological characteristics, RER phenotype and germline p53 and E-cadherin mutations. Carcinogenesis. 1999;20:1127–31.

    CAS  PubMed  Google Scholar 

  99. Oliveira C, Bordin MC, Grehan N, et al. Screening E-cadherin in gastric cancer families reveals germline mutations only in hereditary diffuse gastric cancer kindred. Hum Mutat. 2002;19:510–7.

    CAS  PubMed  Google Scholar 

  100. Moreira-Nunes CA, Barros MB, do Nascimento Borges B, et al. Genetic screening analysis of patients with hereditary diffuse gastric cancer from northern and northeastern Brazil. Hered Cancer Clin Pract. 2014;12(1):1–8.

    Google Scholar 

  101. Figueiredo C, Machado JC, Pharoah P, et al. Helicobacter pylori and interleukin 1 genotyping: an opportunity to identify high-risk individuals for gastric carcinoma. J Natl Cancer Inst. 2002;94:1680–7.

    CAS  PubMed  Google Scholar 

  102. Machado JC, Figueiredo C, Canedo P, et al. A proinflammatory genetic profile increases the risk for chronic atrophic gastritis and gastric carcinoma. Gastroenterology. 2003;125:364–71.

    CAS  PubMed  Google Scholar 

  103. Grady WM, Willis J, Guilford PJ, et al. Methylation of the CDH1 promoter as the second genetic hit in hereditary diffuse gastric cancer. Nat Genet. 2000;26:16–7.

    CAS  PubMed  Google Scholar 

  104. Van Roy F, Berx G. The cell-cell adhesion molecule E-cadherin. Cell Mol Life Sci. 2008;65:3756–88.

    CAS  PubMed  Google Scholar 

  105. Carvalho S, Catarino TA, Dias AM, et al. Preventing E-cadherin aberrant N-glycosylation at Asn-554 improves its critical function in gastric cancer. Oncogene. 2016;35(13):1619–31.

    CAS  PubMed  Google Scholar 

  106. Hannon GJ, Rivas FV, Murchison EP, Steitz JA. The expanding universe of noncoding RNAs. Cold Spring Harb Symp Quant Biol. 2006;71:551–64.

    CAS  PubMed  Google Scholar 

  107. Bannister AJ, Kouzarides T. Regulation of chromatin by histone modifications. Cell Res. 2011;21:381–95.

    CAS  PubMed  PubMed Central  Google Scholar 

  108. Waddington CH. The epigenotype. 1942. Int J Epidemiol. 2012;41:10–3.

    CAS  PubMed  Google Scholar 

  109. Laird PW. Principles and challenges of genome-wide DNA methylation analysis. Nat Rev Genet. 2010;11(3):191–203.

    CAS  PubMed  Google Scholar 

  110. Portela A, Esteller M. Epigenetic modifications and human disease. Nat Biotechnol. 2010;28(10):1057–68.

    CAS  PubMed  Google Scholar 

  111. Virani S, Colacino JA, Kim JH, Rozek LS. Cancer epigenetics: a brief review. ILAR J. 2012;53:359–69.

    PubMed  PubMed Central  Google Scholar 

  112. Santos JC, Ribeiro ML. Epigenetic regulation of DNA repair machinery in Helicobacter pylori-induced gastric carcinogenesis. World J Gastroenterol. 2015;21:9021–37.

    CAS  PubMed  PubMed Central  Google Scholar 

  113. Villano JL, Seery TE, Bressler LR. Temozolomide in malignant gliomas: current use and future targets. Cancer Chemother Pharmacol. 2009;64:647–55.

    CAS  PubMed  Google Scholar 

  114. Roy S, Lahiri D, Maji T, Biswas J. Recurrent Glioblastoma: where we stand. South Asian J Cancer. 2015;4:163–73.

    PubMed  PubMed Central  Google Scholar 

  115. Riemenschneider MJ, Hegi ME, Reifenberger G. MGMT promoter methylation in malignant gliomas. Target Oncol. 2010;5(3):161–5.

    PubMed  Google Scholar 

  116. Jordan JT, Gerstner ER, Batchelor TT, Cahill DP, Plotkin SR. Glioblastoma care in the elderly. Cancer. 2016;122:189–97.

    PubMed  Google Scholar 

  117. Weller M, Stupp R, Reifenberger G, et al. MGMT promoter methylation in malignant gliomas: ready for personalized medicine? Nat Rev Neurol. 2010;6(1):39–51.

    CAS  PubMed  Google Scholar 

  118. Trindade V, Picarelli H, Figueiredo EG, Teixeira MJ. Gliomas: marcadores tumorais e prognóstico. Arq Bras Neurocir. 2012;31:91–4.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratory of Molecular Biology, Ophir Loyola Hospital, Av. Governador Magalhães Barata 992, Belém, Pará, 66063-240, Brazil

    Carla de Castro Sant’ Anna, Alberto Gomes Ferreira Junior, Paulo Soares, Fabricio Tuji, Eric Paschoal, Luiz Cláudio Chaves & Rommel Rodriguez Burbano

  2. João de Barros Barreto University Hospital, Belém, Pará, Brazil

    Carla de Castro Sant’ Anna

Authors
  1. Carla de Castro Sant’ Anna
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alberto Gomes Ferreira Junior
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Paulo Soares
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Fabricio Tuji
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Eric Paschoal
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Luiz Cláudio Chaves
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Rommel Rodriguez Burbano
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Carla de Castro Sant’ Anna.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical standards

As the review study did not include any personal data, the Ophir Loyola Hospital does not require submission to the ethics in research committee or any other form of institutional review.

Informed consent

As this manuscript is a literature review, informed consent is not applicable.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

de Castro Sant’ Anna, C., Junior, A.G.F., Soares, P. et al. Molecular biology as a tool for the treatment of cancer. Clin Exp Med 18, 457–464 (2018). https://doi.org/10.1007/s10238-018-0518-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10238-018-0518-1

Keywords

Search

Navigation