Genome Editing in Cancer Research and Cure

  • Sabin AslamEmail author
  • Sarmad Mehmood


With the advent of genome-editing technologies, targeting genome engineering is no longer a hypothetical abstract. As application area of genome-editing tools is extending beyond the limits of research and biomedical remedies, specific ethical apprehensions are prevalent around the global community about the appropriate scope of genome-editing tools to be used. Genome-editing tools, i.e., meganucleases, zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and clustered regularly interspersed short palindromic repeats (CRISPR/Cas system), accelerate cancer research not only in its base study as well as in its cure by dissecting the mechanism of tumor development, categorizing targets for drug progression, and identifying arm cells for cell-dependent therapies. Current applications of cancer research and cure are discussed in this chapter. Moreover, it has also been discussed that genome editing is the possible cause of enhancing the risk of cancer development.


Genome editing Meganucleases ZFN TALENs CRISPR/Cas system 


  1. 1.
    Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68(6):394–424CrossRefGoogle Scholar
  2. 2.
    Pan F, Pan D, Pardoll DM, Barbi J, Fu J (2019) Compositions and methods for targeting activin signaling to treat cancer. Google PatentsGoogle Scholar
  3. 3.
    Singer M, Wang C, Cong L, Marjanovic ND, Kowalczyk MS, Zhang H, Nyman J, Sakuishi K, Kurtulus S, Gennert D (2016) A distinct gene module for dysfunction uncoupled from activation in tumor-infiltrating T cells. Cell 166(6):1500–1511.e9PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Beloribi-Djefaflia S, Vasseur S, Guillaumond F (2016) Lipid metabolic reprogramming in cancer cells. Oncogene 5(1):e189CrossRefGoogle Scholar
  5. 5.
    Beguin E (2018) Sonodynamic therapy of hypoxic tumours. University of Oxford, OxfordGoogle Scholar
  6. 6.
    Grossman DC, Curry SJ, Owens DK, Barry MJ, Davidson KW, Doubeni CA, Epling JW, Kemper AR, Krist AH, Kurth AE (2018) Screening for ovarian cancer: US preventive services task force recommendation statement. JAMA 319(6):588–594PubMedCrossRefGoogle Scholar
  7. 7.
    Sasieni PD, Parkin DM (2018) Global perspectives surrounding cancer prevention and screening. In: Cancer prevention and screening: concepts, principles and controversies, p 1Google Scholar
  8. 8.
    Thompson R, Mitrou G, Brown S, Almond E, Bandurek I, Brockton N, Kälfors M, McGinley-Gieser D, Sinclair B, Meincke L (2018) Major new review of global evidence on diet, nutrition and physical activity: a blueprint to reduce cancer risk. Nutr Bull 43(3):269–283CrossRefGoogle Scholar
  9. 9.
    Knoll LJ, Hogan DA, Leong JM, Heitman J, Condit RC (2018) Pearls collections: what we can learn about infectious disease and cancer. PLoS Pathog 14(3):e1006915. Scholar
  10. 10.
    Siegel RL, Miller KD, Jemal A (2019) Cancer statistics, 2019. CA Cancer J Clin 69(1):7–34CrossRefGoogle Scholar
  11. 11.
    Fitzmaurice C, Akinyemiju TF, Al Lami FH, Alam T, Alizadeh-Navaei R, Allen C, Alsharif U, Alvis-Guzman N, Amini E, Anderson BO (2018) Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 29 cancer groups, 1990 to 2016: a systematic analysis for the global burden of disease study. JAMA Oncol 4(11):1553–1568CrossRefGoogle Scholar
  12. 12.
    Doubeni CA, Gabler NB, Wheeler CM, McCarthy AM, Castle PE, Halm EA, Schnall MD, Skinner CS, Tosteson AN, Weaver DL (2018) Timely follow-up of positive cancer screening results: a systematic review and recommendations from the PROSPR consortium. CA Cancer J Clin 68(3):199–216PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Gapstur SM, Drope JM, Jacobs EJ, Teras LR, McCullough ML, Douglas CE, Patel AV, Wender RC, Brawley OW (2018) A blueprint for the primary prevention of cancer: targeting established modifiable risk factors. CA Cancer J Clin 68(6):446–470PubMedCrossRefPubMedCentralGoogle Scholar
  14. 14.
    Forman D, Bauld L, Bonanni B, Brenner H, Brown K, Dillner J, Kampman E, Manczuk M, Riboli E, Steindorf K (2018) Time for a European initiative for research to prevent cancer: a manifesto for Cancer Prevention Europe (CPE). J Cancer Policy 17:15–23CrossRefGoogle Scholar
  15. 15.
    Vargo JA, Moiseenko V, Grimm J, Caudell J, Clump DA, Yorke E, Xue J, Vinogradskiy Y, Moros EG, Mavroidis P (2018) Head and neck tumor control probability: radiation dose–volume effects in stereotactic body radiation therapy for locally recurrent previously-irradiated head and neck cancer: report of the AAPM working group. Int J Radiat Oncol Biol Phys.
  16. 16.
    Alam A, Farooq U, Singh R, Dubey V, Kumar S, Kumari R, Kumar K, Naik B, Dhar K (2018) Chemotherapy treatment and strategy schemes: a review. J Toxicol 2(7):555600. Scholar
  17. 17.
    Miller KD, Siegel RL, Lin CC, Mariotto AB, Kramer JL, Rowland JH, Stein KD, Alteri R, Jemal A (2016) Cancer treatment and survivorship statistics, 2016. CA Cancer J Clin 66(4):271–289CrossRefGoogle Scholar
  18. 18.
    Perkins A, Liu G (2016) Primary brain tumors in adults: diagnosis and treatment. Am Fam Physician 93(3):211–217PubMedPubMedCentralGoogle Scholar
  19. 19.
    Hecht SS, Carmella SG, Murphy SE, Stepanov I, Balbo S, Hatsukami DK, Yuan J-M, Park SL, Stram DO, Haiman C (2016) Tobacco smoke toxicant and carcinogen biomarkers and lung cancer susceptibility in smokers. J Thorac Oncol 11(2):S7–S8CrossRefGoogle Scholar
  20. 20.
    Gazdar AF, Zhou C (2018) Lung cancer in never-smokers: a different disease. In: IASLC thoracic oncology. Elsevier, pp 23–29.e23Google Scholar
  21. 21.
    Kuper H, Adami HO, Boffetta P (2002) Tobacco use, cancer causation and public health impact. J Intern Med 251(6):455–466PubMedCrossRefPubMedCentralGoogle Scholar
  22. 22.
    Kushi LH, Byers T, Doyle C, Bandera EV, McCullough M, Gansler T, Andrews KS, Thun MJ (2006) American Cancer Society guidelines on nutrition and physical activity for cancer prevention: reducing the risk of cancer with healthy food choices and physical activity. CA Cancer J Clin 56(5):254–281PubMedCrossRefPubMedCentralGoogle Scholar
  23. 23.
    Park S, Bae J, Nam B-H, Yoo K-Y (2008) Aetiology of cancer in Asia. Asian Pac J Cancer Prev 9(3):371–380PubMedPubMedCentralGoogle Scholar
  24. 24.
    Pagano JS, Blaser M, Buendia M-A, Damania B, Khalili K, Raab-Traub N, Roizman B (2004) Infectious agents and cancer: criteria for a causal relation. In: Seminars in cancer biology, vol 6. Elsevier, Amsterdam, pp 453–471Google Scholar
  25. 25.
    Sonker P, Tewari AK, Chaube SK, Kumar R, Sharma VP, Sonker A, Yadav P (2018) A study on cancer and its drugs with their molecular structure and mechanism of action: A Review. World J Pharm Sci 6(7):13–34Google Scholar
  26. 26.
    Samaras V, Rafailidis PI, Mourtzoukou EG, Peppas G, Falagas ME (2010) Chronic bacterial and parasitic infections and cancer: a review. J Infect Dev Ctries 4(05):267–281PubMedCrossRefPubMedCentralGoogle Scholar
  27. 27.
    Brenner DJ, Hall EJ (2007) Computed tomography—an increasing source of radiation exposure. N Engl J Med 357(22):2277–2284PubMedCrossRefPubMedCentralGoogle Scholar
  28. 28.
    Roukos DH (2009) Genome-wide association studies: how predictable is a person’s cancer risk? Expert Rev Anticancer Ther 9(4):389–392PubMedCrossRefPubMedCentralGoogle Scholar
  29. 29.
    Green J, Cairns BJ, Casabonne D, Wright FL, Reeves G, Beral V, collaborators MWS (2011) Height and cancer incidence in the Million Women Study: prospective cohort, and meta-analysis of prospective studies of height and total cancer risk. Lancet Oncol 12(8):785–794PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Forschungsgemeinschaft D (2015) Carcinogenic substances. In: List of MAK and BAT values 2015: permanent senate commission for the investigation of health hazards of chemical compounds in the work area, pp 163–181Google Scholar
  31. 31.
    Jeon S-Y, Hwang K-A, Choi K-C (2016) Effect of steroid hormones, estrogen and progesterone, on epithelial mesenchymal transition in ovarian cancer development. J Steroid Biochem Mol Biol 158:1–8PubMedCrossRefGoogle Scholar
  32. 32.
    Breitling R, Takano E (2016) Synthetic biology of natural products. Cold Spring Harb Perspect Biol 8(10):a023994PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Carroll D, Golic MM, Bibikova M, Drews G, Golic KG (2016) Targeted chromosomal mutagenesis using zinc finger nucleases. Google PatentsGoogle Scholar
  34. 34.
    Forsyth A, Weeks T, Richael C, Duan H (2016) Transcription activator-like effector nucleases (TALEN)-mediated targeted DNA insertion in potato plants. Front Plant Sci 7:1572PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Huang M, Zhou X, Wang H, Xing D (2018) Clustered regularly interspaced short palindromic repeats/Cas9 triggered isothermal amplification for site-specific nucleic acid detection. Anal Chem 90(3):2193–2200PubMedCrossRefPubMedCentralGoogle Scholar
  36. 36.
    Smith JJ, Jantz D, Hellinga HW (2011) Rationally-designed meganucleases with altered sequence specificity and DNA-binding affinity. Google PatentsGoogle Scholar
  37. 37.
    Baker M (2011) Gene-editing nucleases. Nature Publishing Group, LondonGoogle Scholar
  38. 38.
    Bosley KS, Botchan M, Bredenoord AL, Carroll D, Charo RA, Charpentier E, Cohen R, Corn J, Doudna J, Feng G (2015) CRISPR germline engineering—the community speaks. Nat Biotechnol 33(5):478PubMedCrossRefGoogle Scholar
  39. 39.
    Stoddard BL (2005) Homing endonuclease structure and function. Q Rev Biophys 38(1):49–95PubMedCrossRefPubMedCentralGoogle Scholar
  40. 40.
    Loong SLE (2005) Late Radiation Morbidity Incidence in a South-East Scottish cohort and investigation into abnormalities in DNA double-strand break repair and damage response. Edinburgh Medical School thesis.
  41. 41.
    De Souza N (2011) Primer: genome editing with engineered nucleases. Nat Methods 9(1):27CrossRefGoogle Scholar
  42. 42.
    Smith J, Grizot S, Arnould S, Duclert A, Epinat J-C, Chames P, Prieto J, Redondo P, Blanco FJ, Bravo J (2006) A combinatorial approach to create artificial homing endonucleases cleaving chosen sequences. Nucleic Acids Res 34(22):e149–e149PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Seligman LM, Chisholm KM, Chevalier BS, Chadsey MS, Edwards ST, Savage JH, Veillet AL (2002) Mutations altering the cleavage specificity of a homing endonuclease. Nucleic Acids Res 30(17):3870–3879PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Chevalier BS, Kortemme T, Chadsey MS, Baker D, Monnat RJ Jr, Stoddard BL (2002) Design, activity, and structure of a highly specific artificial endonuclease. Mol Cell 10(4):895–905PubMedCrossRefPubMedCentralGoogle Scholar
  45. 45.
    Arnould S, Chames P, Perez C, Lacroix E, Duclert A, Epinat J-C, Stricher F, Petit A-S, Patin A, Guillier S (2006) Engineering of large numbers of highly specific homing endonucleases that induce recombination on novel DNA targets. J Mol Biol 355(3):443–458PubMedCrossRefPubMedCentralGoogle Scholar
  46. 46.
    Ashworth J, Taylor GK, Havranek JJ, Quadri SA, Stoddard BL, Baker D (2010) Computational reprogramming of homing endonuclease specificity at multiple adjacent base pairs. Nucleic Acids Res 38(16):5601–5608PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Redondo P, Prieto J, Munoz IG, Alibés A, Stricher F, Serrano L, Cabaniols J-P, Daboussi F, Arnould S, Perez C (2008) Molecular basis of xeroderma pigmentosum group C DNA recognition by engineered meganucleases. Nature 456(7218):107PubMedCrossRefPubMedCentralGoogle Scholar
  48. 48.
    Aslam S, Khan SH, Ahmed A, Dandekar AM (2019) Genome editing tools: need of the current era. Am J Mol Biol 9(3):85–109CrossRefGoogle Scholar
  49. 49.
    Rebar EJ, Huang Y, Hickey R, Nath AK, Meoli D, Nath S, Chen B, Xu L, Liang Y, Jamieson AC (2002) Induction of angiogenesis in a mouse model using engineered transcription factors. Nat Med 8(12):1427PubMedCrossRefPubMedCentralGoogle Scholar
  50. 50.
    Kim Y-G, Cha J, Chandrasegaran S (1996) Hybrid restriction enzymes: zinc finger fusions to Fok I cleavage domain. Proc Natl Acad Sci 93(3):1156–1160PubMedCrossRefPubMedCentralGoogle Scholar
  51. 51.
    Cox DBT, Platt RJ, Zhang F (2015) Therapeutic genome editing: prospects and challenges. Nat Med 21(2):121PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Reik A, Zhou Y, Wagner J, Hamlett A, Mendel M, Liu P-Q, Lee G, Paschon D, Rebar E, Ando D (2008) Zinc finger nucleases targeting the glucocorticoid receptor allow IL-13 zetakine transgenic CTLs to kill glioblastoma cells in vivo in the presence of immunosuppressing glucocorticoids. AACR Annual Meeting, San Diego, CAGoogle Scholar
  53. 53.
    Holt N, Wang J, Kim K, Friedman G, Wang X, Taupin V, Crooks GM, Kohn DB, Gregory PD, Holmes MC (2010) Human hematopoietic stem/progenitor cells modified by zinc-finger nucleases targeted to CCR5 control HIV-1 in vivo. Nat Biotechnol 28(8):839PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Gaj T, Gersbach CA, Barbas CF III (2013) ZFN, TALEN, and CRISPR/Cas-based methods for genome engineering. Trends Biotechnol 31(7):397–405PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Pérez-Quintero AL, Rodriguez-R LM, Dereeper A, López C, Koebnik R, Szurek B, Cunnac S (2013) An improved method for TAL effectors DNA-binding sites prediction reveals functional convergence in TAL repertoires of Xanthomonas oryzae strains. PLoS One 8(7):e68464PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Aliyari R, Ding SW (2009) RNA-based viral immunity initiated by the dicer family of host immune receptors. Immunol Rev 227(1):176–188PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Barrangou R (2015) The roles of CRISPR–Cas systems in adaptive immunity and beyond. Curr Opin Immunol 32:36–41PubMedCrossRefPubMedCentralGoogle Scholar
  58. 58.
    Zhang F, Wen Y, Guo X (2014) CRISPR/Cas9 for genome editing: progress, implications and challenges. Hum Mol Genet 23(R1):R40–R46PubMedCrossRefPubMedCentralGoogle Scholar
  59. 59.
    Sternberg SH, Doudna JA (2015) Expanding the biologist’s toolkit with CRISPR-Cas9. Mol Cell 58(4):568–574PubMedCrossRefPubMedCentralGoogle Scholar
  60. 60.
    Barrangou R, Fremaux C, Deveau H, Richards M, Boyaval P, Moineau S, Romero DA, Horvath P (2007) CRISPR provides acquired resistance against viruses in prokaryotes. Science 315(5819):1709–1712CrossRefGoogle Scholar
  61. 61.
    Marraffini LA, Sontheimer EJ (2008) CRISPR interference limits horizontal gene transfer in staphylococci by targeting DNA. Science 322(5909):1843–1845PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Mohanraju P, Makarova KS, Zetsche B, Zhang F, Koonin EV, Van der Oost J (2016) Diverse evolutionary roots and mechanistic variations of the CRISPR-Cas systems. Science 353(6299):aad5147PubMedCrossRefPubMedCentralGoogle Scholar
  63. 63.
    Hille F, Richter H, Wong SP, Bratovič M, Ressel S, Charpentier E (2018) The biology of CRISPR-Cas: backward and forward. Cell 172(6):1239–1259PubMedCrossRefPubMedCentralGoogle Scholar
  64. 64.
    Makarova KS, Wolf YI, Alkhnbashi OS, Costa F, Shah SA, Saunders SJ, Barrangou R, Brouns SJ, Charpentier E, Haft DH (2015) An updated evolutionary classification of CRISPR–Cas systems. Nat Rev Microbiol 13(11):722PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Wright AV, Nuñez JK, Doudna JA (2016) Biology and applications of CRISPR systems: harnessing nature’s toolbox for genome engineering. Cell 164(1–2):29–44CrossRefGoogle Scholar
  66. 66.
    Westra ER, Dowling AJ, Broniewski JM, van Houte S (2016) Evolution and ecology of CRISPR. Annu Rev Ecol Evol Syst 47:307–331CrossRefGoogle Scholar
  67. 67.
    Dugar G, Herbig A, Förstner KU, Heidrich N, Reinhardt R, Nieselt K, Sharma CM (2013) High-resolution transcriptome maps reveal strain-specific regulatory features of multiple Campylobacter jejuni isolates. PLoS Genet 9(5):e1003495PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Hatoum-Aslan A, Maniv I, Marraffini LA (2011) Mature clustered, regularly interspaced, short palindromic repeats RNA (crRNA) length is measured by a ruler mechanism anchored at the precursor processing site. Proc Natl Acad Sci 108(52):21218–21222PubMedCrossRefPubMedCentralGoogle Scholar
  69. 69.
    Yosef I, Goren MG, Qimron U (2012) Proteins and DNA elements essential for the CRISPR adaptation process in Escherichia coli. Nucleic Acids Res 40(12):5569–5576PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Swarts DC, Mosterd C, Van Passel MW, Brouns SJ (2012) CRISPR interference directs strand specific spacer acquisition. PLoS One 7(4):e35888PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Mussolino C, Alzubi J, Fine EJ, Morbitzer R, Cradick TJ, Lahaye T, Bao G, Cathomen T (2014) TALENs facilitate targeted genome editing in human cells with high specificity and low cytotoxicity. Nucleic Acids Res 42(10):6762–6773PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Rinaldo AR, Ayliffe M (2015) Gene targeting and editing in crop plants: a new era of precision opportunities. Mol Breed 35(1):40CrossRefGoogle Scholar
  73. 73.
    Regalado A (2015) CRISPR gene editing to be tested on people by 2017, says Editas. MIT Technol Rev:1–3Google Scholar
  74. 74.
    Cromwell CR, Sung K, Park J, Krysler AR, Jovel J, Kim SK, Hubbard BP (2018) Incorporation of bridged nucleic acids into CRISPR RNAs improves Cas9 endonuclease specificity. Nat Commun 9(1):1448PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Charpentier M, Khedher A, Menoret S, Brion A, Lamribet K, Dardillac E, Boix C, Perrouault L, Tesson L, Geny S (2018) CtIP fusion to Cas9 enhances transgene integration by homology-dependent repair. Nat Commun 9(1):1133PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Chen JS, Dagdas YS, Kleinstiver BP, Welch MM, Sousa AA, Harrington LB, Sternberg SH, Joung JK, Yildiz A, Doudna JA (2017) Enhanced proofreading governs CRISPR–Cas9 targeting accuracy. Nature 550(7676):407PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Hu JH, Miller SM, Geurts MH, Tang W, Chen L, Sun N, Zeina CM, Gao X, Rees HA, Lin Z (2018) Evolved Cas9 variants with broad PAM compatibility and high DNA specificity. Nature 556(7699):57PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Sakuma T, Yamamoto T (2018) Acceleration of cancer science with genome editing and related technologies. Cancer Sci 109(12):3679PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Haapaniemi E, Botla S, Persson J, Schmierer B, Taipale J (2018) CRISPR–Cas9 genome editing induces a p53-mediated DNA damage response. Nat Med 24(7):927PubMedCrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2020

Authors and Affiliations

  1. 1.Department of Plant ScienceUniversity of California, DavisDavisUSA
  2. 2.University of Agriculture FaisalabadFaisalabadPakistan
  3. 3.Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and TechnologyIslamabadPakistan
  4. 4.Department of Pathology, CMH Institute of Medical SciencesBahawalpurPakistan

Personalised recommendations