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CRISPR/Cas9 for overcoming drug resistance in solid tumors

  • Ali Saber
  • Bin Liu
  • Pirooz Ebrahimi
  • Hidde J. HaismaEmail author
Review Article

Abstract

Objectives

In this review, we focus on the application of clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated nuclease 9 (Cas9), as a powerful genome editing system, in the identification of resistance mechanisms and in overcoming drug resistance in the most frequent solid tumors.

Data acquisition

Data were collected by conducting systematic searching of scientific English literature using specific keywords such as “cancer”, “CRISPR” and related combinations.

Results

The review findings revealed the importance of CRISPR/Cas9 system in understanding drug resistance mechanisms and identification of resistance-related genes such as PBRM1, SLFN11 and ATPE1 in different cancers. We also provided an overview of genes, including RSF1, CDK5, and SGOL1, whose disruption can synergize with the currently available drugs such as paclitaxel and sorafenib.

Conclusion

The data suggest CRISPR/Cas9 system as a useful tool in elucidating the molecular basis of drug resistance and improving clinical outcomes.

Graphical abstract

The mechanisms of CRISPR/Cas9-mediated genome editing and double-strand breaks (DSBs) repair.

Keywords

Solid tumor CRISPR/Cas9 Targeted therapy Drug resistance Drug response Clinical outcome 

Notes

Compliance with ethical standards

Competing interests

The authors declare that they have no competing interests.

References

  1. 1.
    Yachida S, Jones S, Bozic I, Antal T, Leary R, Fu B, et al. Distant metastasis occurs late during the genetic evolution of pancreatic cancer. Nature. 2010;467:1114–7.CrossRefPubMedGoogle Scholar
  2. 2.
    Torti D, Trusolino L. Oncogene addiction as a foundational rationale for targeted anti-cancer therapy: promises and perils. EMBO Mol Med. 2011;3:623–36.CrossRefPubMedGoogle Scholar
  3. 3.
    van der Wekken AJ, Saber A, Hiltermann TJN, Kok K, van den Berg A, Groen HJM. Resistance mechanisms after tyrosine kinase inhibitors afatinib and crizotinib in non-small cell lung cancer, a review of the literature. Crit Rev Oncol Hematol. 2016;100:107–16.CrossRefPubMedGoogle Scholar
  4. 4.
    Saber A, Van Der Wekken AJ, Kok K, Terpstra MM, Bosman LJ, Mastik MF, et al. Genomic aberrations in crizotinib resistant lung adenocarcinoma samples identified by transcriptome sequencing. PLoS One. 2016;11(4):e0153065.CrossRefPubMedGoogle Scholar
  5. 5.
    Saber A, van der Wekken A, Hiltermann TJN, Kok K, van den Berg A, Groen HJM. Genomic aberrations guiding treatment of non-small cell lung cancer patients. Cancer Treat Commun. 2015;4:23–33.CrossRefGoogle Scholar
  6. 6.
    Mansoori B, Mohammadi A, Davudian S, Shirjang S, Baradaran B. The different mechanisms of Cancer drug resistance: a brief review. Adv Pharm Bull. 2017;7:339–48.CrossRefPubMedGoogle Scholar
  7. 7.
    Saber A, Hiltermann TJN, Kok K, Terpstra MM, de Lange K, Timens W, et al. Mutation patterns in small cell and non-small cell lung cancer patients suggest a different level of heterogeneity between primary and metastatic tumors. Carcinogenesis. 2017;38(2):144–51.PubMedGoogle Scholar
  8. 8.
    Hegge B, Sjøttem E, Mikkola I. Generation of a PAX6 knockout glioblastoma cell line with changes in cell cycle distribution and sensitivity to oxidative stress. BMC Cancer. 2018;18:496.CrossRefPubMedGoogle Scholar
  9. 9.
    Anelli V, Villefranc JA, Chhangawala S, Martinez -McFaline R, Riva E, Nguyen A, et al. Oncogenic BRAF disrupts thyroid morphogenesis and function via twist expression. elife. 2017;6.Google Scholar
  10. 10.
    Maddalo D, Manchado E, Concepcion CP, Bonetti C, Vidigal JA, Han Y-C, et al. In vivo engineering of oncogenic chromosomal rearrangements with the CRISPR/Cas9 system. Nature. 2014;516:423–7.CrossRefPubMedGoogle Scholar
  11. 11.
    Park M-Y, Jung MH, Eo EY, Kim S, Lee SH, Lee YJ, et al. Generation of lung cancer cell lines harboring EGFR T790M mutation by CRISPR/Cas9-mediated genome editing. Oncotarget. 2017;8.Google Scholar
  12. 12.
    Krall EB, Wang B, Munoz DM, Ilic N, Raghavan S, Niederst MJ, et al. KEAP1 loss modulates sensitivity to kinase targeted therapy in lung cancer. elife. 2017;6.Google Scholar
  13. 13.
    Thu KL, Silvester J, Elliott MJ, Ba-alawi W, Duncan MH, Elia AC, et al. Disruption of the anaphase-promoting complex confers resistance to TTK inhibitors in triple-negative breast cancer. Proc Natl Acad Sci. 2018;115:E1570–7.CrossRefPubMedGoogle Scholar
  14. 14.
    Zhan T, Rindtorff N, Betge J, Ebert MP, Boutros M. CRISPR/Cas9 for cancer research and therapy. Semin Cancer Biol. 2018.Google Scholar
  15. 15.
    Chen Y, Zhang Y. Application of the CRISPR/Cas9 system to drug resistance in breast Cancer. Adv Sci. 2018;5:1700964.CrossRefGoogle Scholar
  16. 16.
    Chen P, You L, Lu Y. Applications of CRISPR-Cas9 Technology in Translational Research on solid-tumor cancers. Cris J. 2018;1:47–54.CrossRefGoogle Scholar
  17. 17.
    Xiao-Jie L, Hui-Ying X, Zun-Ping K, Jin-Lian C, Li-Juan J. CRISPR-Cas9: a new and promising player in gene therapy. J Med Genet. 2015;52:289–96.CrossRefPubMedGoogle Scholar
  18. 18.
    Liu B, Xu H, Miao J, Zhang A, Kou X, Li W, et al. CRISPR/Cas: a faster and more efficient gene editing system. J Nanosci Nanotechnol. 2015;15:1946–59.CrossRefPubMedGoogle Scholar
  19. 19.
    Hsu PD, Scott DA, Weinstein JA, Ran FA, Konermann S, Agarwala V, et al. DNA targeting specificity of RNA-guided Cas9 nucleases. Nat Biotechnol. Nature publishing group, a division of Macmillan publishers limited. All Rights Reserved. 2013;31:827.Google Scholar
  20. 20.
    Hu JH, Miller SM, Geurts MH, Tang W, Chen L, Sun N, et al. Evolved Cas9 variants with broad PAM compatibility and high DNA specificity. Nature. Macmillan publishers limited, part of springer nature. All Rights Reserved. 2018;556:57.Google Scholar
  21. 21.
    Vogelstein B, Papadopoulos N, Velculescu VE, Zhou S, Diaz LA, Kinzler KW. Cancer genome landscapes. Science (80- ). 2013;339:1546–58.CrossRefPubMedGoogle Scholar
  22. 22.
    Planchard D. Identification of driver mutations in lung cancer: first step in personalized cancer. Target Oncol. 2013;8:3–14.CrossRefPubMedGoogle Scholar
  23. 23.
    Floc’h N, Martin MJ, Riess JW, Orme JP, Staniszewska AD, Ménard L, et al. Antitumor activity of Osimertinib, an irreversible mutant-selective EGFR tyrosine kinase inhibitor, in NSCLC harboring EGFR exon 20 insertions. Mol Cancer Ther. 2018;17:885–96.CrossRefPubMedGoogle Scholar
  24. 24.
    Terai H, Kitajima S, Potter DS, Matsui Y, Quiceno LG, Chen T, et al. ER stress signaling promotes the survival of Cancer “Persister cells” tolerant to EGFR tyrosine kinase inhibitors. Cancer Res. 2018;78:1044–57.CrossRefPubMedGoogle Scholar
  25. 25.
    Yu J, Zhou J, Xu F, Bai W, Zhang W. High expression of Aurora-B is correlated with poor prognosis and drug resistance in non-small cell lung cancer. Int J Biol Markers. 2018;33:215–21.CrossRefPubMedGoogle Scholar
  26. 26.
    Chen X, Sun X, Guan J, Gai J, Xing J, Fu L, et al. Rsf-1 influences the sensitivity of non-small cell lung Cancer to paclitaxel by regulating NF-κB pathway and its downstream proteins. Cell Physiol Biochem. 2017;44:2322–36.CrossRefPubMedGoogle Scholar
  27. 27.
    Liao S, Davoli T, Leng Y, Li MZ, Xu Q, Elledge SJ. A genetic interaction analysis identifies cancer drivers that modify EGFR dependency. Genes Dev. 2017;31:184–96.CrossRefPubMedGoogle Scholar
  28. 28.
    Hussmann D, Madsen AT, Jakobsen KR, Luo Y, Sorensen BS, Nielsen AL. IGF1R depletion facilitates MET-amplification as mechanism of acquired resistance to erlotinib in HCC827 NSCLC cells. Oncotarget. 2017;8:33300–15.CrossRefPubMedGoogle Scholar
  29. 29.
    Kanwal M, Ding X-J, Song X, Zhou G-B, Cao Y. MUC16 overexpression induced by gene mutations promotes lung cancer cell growth and invasion. Oncotarget. 2018;9:12226–39.CrossRefPubMedGoogle Scholar
  30. 30.
    Biswas K, Sarkar S, Du K, Brautigan DL, Abbas T, Larner JM. The E3 ligase CHIP mediates p21 degradation to maintain Radioresistance. Mol Cancer Res. 2017;15:651–9.CrossRefPubMedGoogle Scholar
  31. 31.
    Lok BH, Gardner EE, Schneeberger VE, Ni A, Desmeules P, Rekhtman N, et al. PARP inhibitor activity correlates with SLFN11 expression and demonstrates synergy with Temozolomide in small cell lung Cancer. Clin Cancer Res. 2017;23:523–35.CrossRefPubMedGoogle Scholar
  32. 32.
    Qin S, Ingle JN, Liu M, Yu J, Wickerham DL, Kubo M, et al. Calmodulin-like protein 3 is an estrogen receptor alpha coregulator for gene expression and drug response in a SNP, estrogen, and SERM-dependent fashion. Breast Cancer Res. 2017;19:95.CrossRefPubMedGoogle Scholar
  33. 33.
    Weyburne ES, Wilkins OM, Sha Z, Williams DA, Pletnev AA, de Bruin G, et al. Inhibition of the proteasome β2 site sensitizes triple-negative breast Cancer cells to β5 inhibitors and suppresses Nrf1 activation. Cell Chem Biol. 2017;24:218–30.CrossRefPubMedGoogle Scholar
  34. 34.
    Bajrami I, Marlow R, van de Ven M, Brough R, Pemberton HN, Frankum J, et al. E-cadherin/ROS1 inhibitor synthetic lethality in breast Cancer. Cancer Discov. 2018;8:498–515.CrossRefPubMedGoogle Scholar
  35. 35.
    Peng W, Huang J, Yang L, Gong A, Mo Y-Y. Linc-RoR promotes MAPK/ERK signaling and confers estrogen-independent growth of breast cancer. Mol Cancer. 2017;16:161.CrossRefPubMedGoogle Scholar
  36. 36.
    Bahreini A, Li Z, Wang P, Levine KM, Tasdemir N, Cao L, et al. Mutation site and context dependent effects of ESR1 mutation in genome-edited breast cancer cell models. Breast Cancer Res. 2017;19:60.CrossRefPubMedGoogle Scholar
  37. 37.
    Harrod A, Fulton J, Nguyen VTM, Periyasamy M, Ramos-Garcia L, Lai C-F, et al. Genomic modelling of the ESR1 Y537S mutation for evaluating function and new therapeutic approaches for metastatic breast cancer. Oncogene. 2017;36:2286–96.CrossRefPubMedGoogle Scholar
  38. 38.
    Mao C, Livezey M, Kim JE, Shapiro DJ. Antiestrogen resistant cell lines expressing estrogen receptor α mutations upregulate the unfolded protein response and are killed by BHPI. Sci Rep. 2016;6:34753.CrossRefPubMedGoogle Scholar
  39. 39.
    Chen T, Liu C, Lu H, Yin M, Shao C, Hu X, et al. The expression of APE1 in triple-negative breast cancer and its effect on drug sensitivity of olaparib. Tumor Biol. 2017;39:101042831771339.CrossRefGoogle Scholar
  40. 40.
    Avivar-Valderas A, McEwen R, Taheri-Ghahfarokhi A, Carnevalli LS, Hardaker EL, Maresca M, et al. Functional significance of co-occurring mutations in PIK3CA and MAP3K1 in breast cancer. Oncotarget. 2018;9:21444–58.CrossRefPubMedGoogle Scholar
  41. 41.
    Merino D, Whittle JR, Vaillant F, Serrano A, Gong J-N, Giner G, et al. Synergistic action of the MCL-1 inhibitor S63845 with current therapies in preclinical models of triple-negative and HER2-amplified breast cancer. Sci Transl Med. 2017;9:eaam7049.CrossRefPubMedGoogle Scholar
  42. 42.
    Barazas M, Annunziato S, Pettitt SJ, de Krijger I, Ghezraoui H, Roobol SJ, et al. The CST complex mediates end protection at double-Strand breaks and promotes PARP inhibitor sensitivity in BRCA1-deficient cells. Cell Rep. 2018;23:2107–18.CrossRefPubMedGoogle Scholar
  43. 43.
    Ardelt MA, Fröhlich T, Martini E, Müller M, Kanitz V, Atzberger C, et al. Inhibition of cyclin-dependent kinase 5 - a novel strategy to improve Sorafenib response in HCC therapy. Hepatology 2019;69:376–93.Google Scholar
  44. 44.
    Gao L, Shay C, Lv F, Wang X, Teng Y. Implications of FGF19 on sorafenib-mediated nitric oxide production in hepatocellular carcinoma cells - a short report. Cell Oncol. 2018;41:85–91.CrossRefGoogle Scholar
  45. 45.
    Wang C, Jin H, Gao D, Lieftink C, Evers B, Jin G, et al. Phospho-ERK is a biomarker of response to a synthetic lethal drug combination of sorafenib and MEK inhibition in liver cancer. J Hepatol. 2018;69:1057–65.CrossRefPubMedGoogle Scholar
  46. 46.
    Sun W, He B, Yang B, Hu W, Cheng S, Xiao H, et al. Genome-wide CRISPR screen reveals SGOL1 as a druggable target of sorafenib-treated hepatocellular carcinoma. Lab Investig. 2018;98:734–44.CrossRefPubMedGoogle Scholar
  47. 47.
    Han B, Cai J, Gao W, Meng X, Gao F, Wu P, et al. Loss of ATRX suppresses ATM dependent DNA damage repair by modulating H3K9me3 to enhance temozolomide sensitivity in glioma. Cancer Lett. 2018;419:280–90.CrossRefPubMedGoogle Scholar
  48. 48.
    Han N, Hu G, Shi L, Long G, Yang L, Xi Q, et al. Notch1 ablation radiosensitizes glioblastoma cells. Oncotarget. 2017;8:88059–68.PubMedGoogle Scholar
  49. 49.
    Hoang-Minh LB, Deleyrolle LP, Nakamura NS, Parker AK, Martuscello RT, Reynolds BA, et al. PCM1 depletion inhibits glioblastoma cell Ciliogenesis and increases cell death and sensitivity to Temozolomide. Transl Oncol. 2016;9:392–402.CrossRefPubMedGoogle Scholar
  50. 50.
    Ranjan A, Srivastava SK. Penfluridol suppresses glioblastoma tumor growth by Akt-mediated inhibition of GLI1. Oncotarget. 2017;8:32960–76.PubMedGoogle Scholar
  51. 51.
    Makvandi M, Pantel A, Schwartz L, Schubert E, Xu K, Hsieh C-J, et al. A PET imaging agent for evaluating PARP-1 expression in ovarian cancer. J Clin Invest. 2018;128:2116–26.CrossRefPubMedGoogle Scholar
  52. 52.
    Zhao G, Wang Q, Gu Q, Qiang W, Wei J-J, Dong P, et al. Lentiviral CRISPR/Cas9 nickase vector mediated BIRC5 editing inhibits epithelial to mesenchymal transition in ovarian cancer cells. Oncotarget 2017;8:94666–80.Google Scholar
  53. 53.
    Pagotto A, Pilotto G, Mazzoldi EL, Nicoletto MO, Frezzini S, Pastò A, et al. Autophagy inhibition reduces chemoresistance and tumorigenic potential of human ovarian cancer stem cells. Cell Death Dis. 2017;8:e2943.CrossRefPubMedGoogle Scholar
  54. 54.
    Zhao Q, Qian Q, Cao D, Yang J, Gui T, Shen K. Role of BMI1 in epithelial ovarian cancer: investigated via the CRISPR/Cas9 system and RNA sequencing. J Ovarian Res. 2018;11:31.CrossRefPubMedGoogle Scholar
  55. 55.
    Hosain SB, Khiste SK, Uddin MB, Vorubindi V, Ingram C, Zhang S, et al. Inhibition of glucosylceramide synthase eliminates the oncogenic function of p53 R273H mutant in the epithelial-mesenchymal transition and induced pluripotency of colon cancer cells. Oncotarget. 2016;7:60575–92.CrossRefPubMedGoogle Scholar
  56. 56.
    Xia D, Ji W, Xu C, Lin X, Wang X, Xia Y, et al. Knockout of MARCH2 inhibits the growth of HCT116 colon cancer cells by inducing endoplasmic reticulum stress. Cell Death Dis. 2017;8:e2957.CrossRefPubMedGoogle Scholar
  57. 57.
    Zhou M, Liu X, Li Z, Huang Q, Li F, Li C-Y. Caspase-3 regulates the migration, invasion and metastasis of colon cancer cells. Int J Cancer. 2018;143:921–30.CrossRefPubMedGoogle Scholar
  58. 58.
    Wu X-Y, Fang J, Wang Z-J, Chen C, Liu J-Y, Wu G-N, et al. Identification of RING-box 2 as a potential target for combating colorectal cancer growth and metastasis. Am J Cancer Res. 2017;7:1238–51.PubMedGoogle Scholar
  59. 59.
    Awuah SG, Riddell IA, Lippard SJ. Repair shielding of platinum-DNA lesions in testicular germ cell tumors by high-mobility group box protein 4 imparts cisplatin hypersensitivity. Proc Natl Acad Sci. 2017;114:950–5.CrossRefPubMedGoogle Scholar
  60. 60.
    Mou H, Moore J, Malonia SK, Li Y, Ozata DM, Hough S, et al. Genetic disruption of oncogenic Kras sensitizes lung cancer cells to Fas receptor-mediated apoptosis. Proc Natl Acad Sci. 2017;114:3648–53.CrossRefPubMedGoogle Scholar
  61. 61.
    Romero R, Sayin VI, Davidson SM, Bauer MR, Singh SX, LeBoeuf SE, et al. Keap1 loss promotes Kras-driven lung cancer and results in dependence on glutaminolysis. Nat Med 2017;23:1362–8.Google Scholar
  62. 62.
    Wright G, Golubeva V, Remsing Rix LL, Berndt N, Luo Y, Ward GA, et al. Dual targeting of WEE1 and PLK1 by AZD1775 elicits single agent cellular anticancer activity. ACS Chem Biol. 2017;12:1883–92.CrossRefPubMedGoogle Scholar
  63. 63.
    Chen Z, Fillmore CM, Hammerman PS, Kim CF, Wong K-K. Non-small-cell lung cancers: a heterogeneous set of diseases. Nat Rev Cancer. 2014;14:535–46.CrossRefPubMedGoogle Scholar
  64. 64.
    Zheng YZ, Xue MZ, Shen HJ, Li XG, Ma D, Gong Y, et al. PHF5A epigenetically inhibits apoptosis to promote breast cancer progression. Cancer Res 2018;78:3190–206.Google Scholar
  65. 65.
    Goldhirsch A, Winer EP, Coates AS, Gelber RD, Piccart-Gebhart M, Thürlimann B, et al. Personalizing the treatment of women with early breast cancer: highlights of the St Gallen international expert consensus on the primary therapy of early breast Cancer 2013. Ann Oncol. 2013;24:2206–23.CrossRefPubMedGoogle Scholar
  66. 66.
    Bledzka K, Schiemann B, Schiemann WP, Fox P, Plow EF, Sossey-Alaoui K. The WAVE3-YB1 interaction regulates cancer stem cells activity in breast cancer. Oncotarget. 2017;8:104072–89.CrossRefPubMedGoogle Scholar
  67. 67.
    Tu C-F, Wu M-Y, Lin Y-C, Kannagi R, Yang R-B. FUT8 promotes breast cancer cell invasiveness by remodeling TGF-β receptor core fucosylation. Breast Cancer Res. 2017;19:111.CrossRefPubMedGoogle Scholar
  68. 68.
    Goossens N, Sun X, Hoshida Y. Molecular classification of hepatocellular carcinoma: potential therapeutic implications. Hepatic Oncol. 2015;2:371–9.CrossRefGoogle Scholar
  69. 69.
    Moyes KW, Lieberman NAP, Kreuser SA, Chinn H, Winter C, Deutsch G, et al. Genetically engineered macrophages: a potential platform for Cancer immunotherapy. Hum Gene Ther. 2017;28:200–15.CrossRefPubMedGoogle Scholar
  70. 70.
    JOVČEVSKA I, KOČEVAR N, KOMEL R. Glioma and glioblastoma - how much do we (not) know? Mol Clin Oncol. 2013;1:935–41.CrossRefPubMedGoogle Scholar
  71. 71.
    Doebele RC, Pilling AB, Aisner DL, Kutateladze TG, Le AT, Weickhardt AJ, et al. Mechanisms of resistance to Crizotinib in patients with ALK gene rearranged non–small cell lung Cancer. Clin Cancer Res. 2012;18:1472–82.CrossRefPubMedGoogle Scholar
  72. 72.
    Rosell R, Bivona TG, Karachaliou N. Genetics and biomarkers in personalisation of lung cancer treatment. Lancet. 2013;382:720–31.CrossRefPubMedGoogle Scholar
  73. 73.
    Liu B, Zhou L, Wang Q, Li K. A mutation-sensitive switch assay to detect five clinically significant epidermal growth factor receptor mutations. Genet Test Mol Biomarkers. 2015;19:316–23.CrossRefPubMedGoogle Scholar
  74. 74.
    Ferronika P, van den Bos H, Taudt A, Spierings DCJ, Saber A, Hiltermann TJN, et al. Copy number alterations assessed at the single-cell level revealed mono- and polyclonal seeding patterns of distant metastasis in a small-cell lung cancer patient. Ann Oncol. 2017;28:1668–70.CrossRefPubMedGoogle Scholar
  75. 75.
    de Bruin EC, McGranahan N, Mitter R, Salm M, Wedge DC, Yates L, et al. Spatial and temporal diversity in genomic instability processes defines lung cancer evolution. Science (80- ). 2014;346:251–6.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Ali Saber
    • 1
  • Bin Liu
    • 1
  • Pirooz Ebrahimi
    • 2
    • 3
  • Hidde J. Haisma
    • 1
    Email author
  1. 1.Department of Chemical and Pharmaceutical Biology, Groningen Research Institute of PharmacyUniversity of GroningenGroningenThe Netherlands
  2. 2.Universal Scientific Education and Research NetworkTehranIran
  3. 3.Parseh Medical Genetics ClinicTehranIran

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