Skip to content
2000
Volume 32, Issue 13
  • ISSN: 1381-6128
  • E-ISSN: 1873-4286

Abstract

The use of CRISPR-Cas9 to engineer cancer cell lines has made it possible to precisely examine how cancer cells react to different drugs and therapies. Some of the key improvements are in the use of Mediator Complex Subunit 12 (MED12)-knockout cells to study cell resistance to BRAF inhibitors, CRISPR models of epithelial-mesenchymal transition for breast cancer, and pharmacogenomic analysis in various cancer cell lines. CRISPR is used in immunotherapy to help Chimeric Antigen Receptor T (CAR-T) cells function better by disrupting the immune checkpoints like Programmed Cell Death Protein 1 (PD-1) and Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and to adapt T cells to react with various antigens. As a result of these innovations, it is now possible to track how cancers like non-small cell lung cancer (NSCLC) and ovarian cancer evolve, change their epigenetic features, and find strategies to reverse their resistance. Moving forward, integrating AI analytics, single-cell multi-omics, patient-derived organoids, and CRISPR mechanisms will help improve precision oncology and speed up effective treatment planning.

© 2026 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cpd/10.2174/0113816128413220250728182852
2025-08-13
2026-02-28

  • From This Site

    /content/journals/cpd/10.2174/0113816128413220250728182852
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. SwartjesT. StaalsR.H.J. van der OostJ. Editor’s cut: DNA cleavage by CRISPR RNA-guided nucleases Cas9 and Cas12a.Biochem Soc Trans202048120721910.1042/BST2019056331872209
     [Google Scholar]
  2. DeviV. HarjaiK. ChhibberS. CRISPR-Cas systems: Role in cellular processes beyond adaptive immunity.Folia Microbiol202267683785010.1007/s12223‑022‑00993‑235854181
     [Google Scholar]
  3. NieY. LiD. PengY. WangS. HuS. LiuM. DingJ. ZhouW. Metal organic framework coated MnO2 nanosheets delivering doxorubicin and self-activated DNAzyme for chemo-gene combinatorial treatment of cancer.Int J Pharm202058511951310.1016/j.ijpharm.2020.11951332526334
     [Google Scholar]
  4. CharpentierE. MarraffiniL.A. Harnessing CRISPR-Cas9 immunity for genetic engineering.Curr Opin Microbiol20141911411910.1016/j.mib.2014.07.00125048165
     [Google Scholar]
  5. LiZ. FanJ. XiaoY. WangW. ZhenC. PanJ. WuW. LiuY. ChenZ. YanQ. ZengH. LuoS. LiuL. TuZ. ZhaoX. HouY. Essential role of Dhx16-mediated ribosome assembly in maintenance of hematopoietic stem cells.Leukemia202438122699270810.1038/s41375‑024‑02423‑339333759
     [Google Scholar]
  6. HuangH. HuangF. LiangX. FuY. ChengZ. HuangY. ChenZ. DuanY. ChenY. Afatinib reverses emt via inhibiting cd44-stat3 axis to promote radiosensitivity in nasopharyngeal carcinoma.Pharmaceuticals20221613710.3390/ph1601003736678534
     [Google Scholar]
  7. KhajuriaO. SharmaN. Epigenetic targeting for lung cancer treatment via CRISPR/Cas9 technology.Advances in Cancer Biology - Metastasis2021310001210.1016/j.adcanc.2021.100012
     [Google Scholar]
  8. BalonK. SheriffA. JackówJ. ŁaczmańskiŁ. Targeting cancer with crispr/cas9-based therapy.Int J Mol Sci202223157310.3390/ijms2301057335008996
     [Google Scholar]
  9. QianF.C. ZhouL.W. LiY.Y. YuZ.M. LiL.D. WangY.Z. XuM.C. WangQ.Y. LiC.Q. SEanalysis 2.0: A comprehensive super-enhancer regulatory network analysis tool for human and mouse.Nucleic Acids Res202351W1W520W52710.1093/nar/gkad40837194711
     [Google Scholar]
  10. YangH. HeC. BiY. ZhuX. DengD. RanT. JiX. Synergistic effect of VEGF and SDF-1α in endothelial progenitor cells and vascular smooth muscle cells.Front Pharmacol20221391434710.3389/fphar.2022.91434735910392
     [Google Scholar]
  11. ModellA.E. LimD. NguyenT.M. SreekanthV. ChoudharyA. CRISPR-based therapeutics: Current challenges and future applications.Trends Pharmacol Sci202243215116110.1016/j.tips.2021.10.01234952739
     [Google Scholar]
  12. WengerA. KarlssonI. KlingT. CarénH. CRISPR-Cas9 knockout screen identifies novel treatment targets in childhood high-grade glioma.Clin Epigenetics20231518010.1186/s13148‑023‑01498‑637161535
     [Google Scholar]
  13. LinK.H. Using CRISPR/Cas9 screens to define organizing principles that govern drug sensitivity in acute myeloid leukemia.Duke University2020
     [Google Scholar]
  14. HultonC.H. CostaE.A. ShahN.S. Quintanal-VillalongaA. HellerG. de StanchinaE. RudinC.M. PoirierJ.T. Direct genome editing of patient-derived xenografts using CRISPR-Cas9 enables rapid in vivo functional genomics.Nat Can20201335936910.1038/s43018‑020‑0040‑833345196
     [Google Scholar]
  15. YangZ. LiuX. XuH. TeschendorffA.E. XuL. LiJ. FuM. LiuJ. ZhouH. WangY. ZhangL. HeY. LvK. YangH. Integrative analysis of genomic and epigenomic regulation reveals miRNA mediated tumor heterogeneity and immune evasion in lower grade glioma.Commun Biol20247182410.1038/s42003‑024‑06488‑938971948
     [Google Scholar]
  16. YangH. ZhouH. FuM. XuH. HuangH. ZhongM. ZhangM. HuaW. LvK. ZhuG. TMEM64 aggravates the malignant phenotype of glioma by activating the Wnt/β-catenin signaling pathway.Int J Biol Macromol2024260Pt 112933210.1016/j.ijbiomac.2024.12933238232867
     [Google Scholar]
  17. ZychA.O. BajorM. ZagozdzonR. Application of genome editing techniques in immunology.Arch Immunol Ther Exp201866428929810.1007/s00005‑018‑0504‑z29344676
     [Google Scholar]
  18. MeissnerT.B. MandalP.K. FerreiraL.M.R. RossiD.J. CowanC.A. Genome editing for human gene therapy.Methods Enzymol201454627329510.1016/B978‑0‑12‑801185‑0.00013‑125398345
     [Google Scholar]
  19. QasimW. AmroliaP.J. SamarasingheS. GhorashianS. ZhanH. StaffordS. ButlerK. AhsanG. GilmourK. AdamsS. PinnerD. ChiesaR. ChattersS. SwiftS. GouldenN. PeggsK. ThrasherA.J. VeysP. PuleM. First clinical application of Talen Engineered Universal CAR19 T cells in B-ALL.Blood201512623204610.1182/blood.V126.23.2046.2046
     [Google Scholar]
  20. WuX. FuM. GeC. ZhouH. HuangH. ZhongM. ZhangM. XuH. ZhuG. HuaW. LvK. YangH. m6A-Mediated upregulation of lncrna chaserr promotes the progression of glioma by modulating the miR-6893-3p/TRIM14 Axis.Mol Neurobiol20246185418544010.1007/s12035‑023‑03911‑w38193984
     [Google Scholar]
  21. SynN.L. TengM.W.L. MokT.S.K. SooR.A. De-novo and acquired resistance to immune checkpoint targeting.Lancet Oncol20171812e731e74110.1016/S1470‑2045(17)30607‑129208439
     [Google Scholar]
  22. SchumannK. LinS. BoyerE. SimeonovD.R. SubramaniamM. GateR.E. HaliburtonG.E. YeC.J. BluestoneJ.A. DoudnaJ.A. MarsonA. Generation of knock-in primary human T cells using Cas9 ribonucleoproteins.Proc Natl Acad Sci USA201511233104371044210.1073/pnas.151250311226216948
     [Google Scholar]
  23. SuS. HuB. ShaoJ. ShenB. DuJ. DuY. ZhouJ. YuL. ZhangL. ChenF. ShaH. ChengL. MengF. ZouZ. HuangX. LiuB. CRISPR-Cas9 mediated efficient PD-1 disruption on human primary T cells from cancer patients.Sci Rep2016612007010.1038/srep2007026818188
     [Google Scholar]
  24. BaylisF. McLeodM. First-in-human phase 1 CRISPR gene editing cancer trials: Are we ready?Curr Gene Ther201717430931929173170
     [Google Scholar]
  25. YouL. TongR. LiM. LiuY. XueJ. LuY. Advancements and obstacles of crispr-cas9 technology in translational research.Mol Ther Methods Clin Dev20191335937010.1016/j.omtm.2019.02.00830989086
     [Google Scholar]
  26. RothT.L. Puig-SausC. YuR. ShifrutE. CarnevaleJ. LiP.J. HiattJ. SacoJ. KrystofinskiP. LiH. TobinV. NguyenD.N. LeeM.R. PutnamA.L. FerrisA.L. ChenJ.W. SchickelJ.N. PellerinL. CarmodyD. Alkorta-AranburuG. del GaudioD. MatsumotoH. MorellM. MaoY. ChoM. QuadrosR.M. GurumurthyC.B. SmithB. HaugwitzM. HughesS.H. WeissmanJ.S. SchumannK. EsenstenJ.H. MayA.P. AshworthA. KupferG.M. GreeleyS.A.W. BacchettaR. MeffreE. RoncaroloM.G. RombergN. HeroldK.C. RibasA. LeonettiM.D. MarsonA. Reprogramming human T cell function and specificity with non-viral genome targeting.Nature2018559771440540910.1038/s41586‑018‑0326‑529995861
     [Google Scholar]
  27. StadtmauerE.A. FraiettaJ.A. DavisM.M. CohenA.D. WeberK.L. LancasterE. ManganP.A. KulikovskayaI. GuptaM. ChenF. TianL. GonzalezV.E. XuJ. JungI. MelenhorstJ.J. PlesaG. SheaJ. MatlawskiT. CerviniA. GaymonA.L. DesjardinsS. LamontagneA. Salas-MckeeJ. FesnakA. SiegelD.L. LevineB.L. JadlowskyJ.K. YoungR.M. ChewA. HwangW.T. HexnerE.O. CarrenoB.M. NoblesC.L. BushmanF.D. ParkerK.R. QiY. SatpathyA.T. ChangH.Y. ZhaoY. LaceyS.F. JuneC.H. CRISPR-engineered T cells in patients with refractory cancer.Science20203676481eaba736510.1126/science.aba736532029687
     [Google Scholar]
  28. MirabelliP. CoppolaL. SalvatoreM. Cancer cell lines are useful model systems for medical research.Cancers2019118109810.3390/cancers1108109831374935
     [Google Scholar]
  29. SunW. JangM.S. ZhanS. LiuC. ShengL. LeeJ.H. FuY. YangH.Y. Tumor-targeting and redox-responsive photo-cross-linked nanogel derived from multifunctional hyaluronic acid-lipoic acid conjugates for enhanced in vivo protein delivery.Int J Biol Macromol202531414444410.1016/j.ijbiomac.2025.14444440403518
     [Google Scholar]
  30. ZhangG. SongC. YinM. LiuL. ZhangY. LiY. ZhangJ. GuoM. LiC. TRAPT: A multi-stage fused deep learning framework for predicting transcriptional regulators based on large-scale epigenomic data.Nat Commun2025161361110.1038/s41467‑025‑58921‑040240358
     [Google Scholar]
  31. ZhangL. LiY. ChenQ. XiaY. ZhengW. JiangX. The construction of drug-resistant cancer cell lines by CRISPR/Cas9 system for drug screening.Sci Bull201863211411141910.1016/j.scib.2018.09.02436658981
     [Google Scholar]
  32. GonçalvesE. Segura-CabreraA. PaciniC. PiccoG. BehanF.M. JaaksP. CokerE.A. van der MeerD. BarthorpeA. LightfootH. MironenkoT. BeckA. RichardsonL. YangW. LleshiE. HallJ. TolleyC. HallC. MaliI. ThomasF. MorrisJ. LeachA.R. LynchJ.T. SiddersB. CrafterC. IorioF. FawellS. GarnettM.J. Drug mechanism-of-action discovery through the integration of pharmacological and CRISPR screens.Mol Syst Biol2020167e940510.15252/msb.2019940532627965
     [Google Scholar]
  33. BehanF.M. IorioF. PiccoG. GonçalvesE. BeaverC.M. MigliardiG. SantosR. RaoY. SassiF. PinnelliM. AnsariR. HarperS. JacksonD.A. McRaeR. PooleyR. WilkinsonP. van der MeerD. DowD. Buser-DoepnerC. BertottiA. TrusolinoL. StronachE.A. Saez-RodriguezJ. YusaK. GarnettM.J. Prioritization of cancer therapeutic targets using CRISPR–Cas9 screens.Nature2019568775351151610.1038/s41586‑019‑1103‑930971826
     [Google Scholar]
  34. ShuW. KumariS. DouglasD. RodriguezL.G. NewmanR. Abstract 1885: CRISPR/Cas9 engineered immortalized breast epithelial MCF10A reporter line for EMT studies and anti-cancer drug discovery.Cancer Res20197913_Supplement188510.1158/1538‑7445.AM2019‑1885
     [Google Scholar]
  35. Nguyen DD. Targeted modification of major histocompatibility complex class 1 molecules via CRISPR-CAS9. United Kingdom: University of Northumbria at Newcastle 2022.
  36. DasK. EiselD. LenklC. GoyalA. DiederichsS. DickesE. OsenW. EichmüllerS.B. Correction: Generation of murine tumor cell lines deficient in MHC molecule surface expression using the CRISPR/Cas9 system.PLoS One20181312e020971910.1371/journal.pone.020971930566524
     [Google Scholar]
  37. GengC. RajapaksheK. ShahS.S. ShouJ. EedunuriV.K. FoleyC. FiskusW. RajendranM. ChewS.A. ZimmermannM. BondR. HeB. CoarfaC. MitsiadesN. Correction: Androgen receptor is the key transcriptional mediator of the tumor suppressor spop in prostate cancer.Cancer Res20197917455210.1158/0008‑5472.CAN‑19‑198131481421
     [Google Scholar]
  38. DrostJ. van JaarsveldR.H. PonsioenB. ZimberlinC. van BoxtelR. BuijsA. SachsN. OvermeerR.M. OfferhausG.J. BegthelH. KorvingJ. van de WeteringM. SchwankG. LogtenbergM. CuppenE. SnippertH.J. MedemaJ.P. KopsG.J.P.L. CleversH. Sequential cancer mutations in cultured human intestinal stem cells.Nature20155217550434710.1038/nature1441525924068
     [Google Scholar]
  39. MatanoM. DateS. ShimokawaM. TakanoA. FujiiM. OhtaY. WatanabeT. KanaiT. SatoT. Modeling colorectal cancer using CRISPR-Cas9–mediated engineering of human intestinal organoids.Nat Med201521325626210.1038/nm.380225706875
     [Google Scholar]
  40. LinM. YangZ. YangY. PengY. LiJ. DuY. SunQ. GaoD. YuanQ. ZhouY. ChenX. QiX. CRISPR-based in situ engineering tumor cells to reprogram macrophages for effective cancer immunotherapy.Nano Today20224210135910.1016/j.nantod.2021.101359
     [Google Scholar]
  41. SmithJ. BanerjeeR. WalyR. UrbanoA. GimenezG. DayR. EcclesM.R. WeeksR.J. ChatterjeeA. Locus-specific DNA methylation editing in melanoma cell lines using a CRISPR-based system.Cancers20211321543310.3390/cancers1321543334771597
     [Google Scholar]
  42. XuC. JiangS. MaX. JiangZ. PanY. LiX. ZhangL. ZhouH. ChenS. XingX. ChenL. FuW. WangQ. ChenW. LiD. CRISPR-based DNA methylation editing of NNT rescues the cisplatin resistance of lung cancer cells by reducing autophagy.Arch Toxicol202397244145610.1007/s00204‑022‑03404‑036336710
     [Google Scholar]
  43. WaltonJ. BlagihJ. EnnisD. LeungE. DowsonS. FarquharsonM. TookmanL.A. OrangeC. AthineosD. MasonS. StevensonD. BlythK. StrathdeeD. BalkwillF.R. VousdenK. LockleyM. McNeishI.A. CRISPR/Cas9-Mediated Trp53 and Brca2 knockout to generate improved murine models of ovarian high-grade serous carcinoma.Cancer Res201676206118612910.1158/0008‑5472.CAN‑16‑127227530326
     [Google Scholar]
  44. EleveldT.F. BakaliC. EijkP.P. StathiP. VriendL.E. PoddigheP.J. YlstraB. Engineering large-scale chromosomal deletions by CRISPR-Cas9.Nucleic Acids Res20214921120071201610.1093/nar/gkab55734230973
     [Google Scholar]
  45. ParkM.Y. JungM.H. EoE.Y. KimS. LeeS.H. LeeY.J. ParkJ.S. ChoY.J. ChungJ.H. KimC.H. Il YoonH. LeeJ.H. LeeC.T. Generation of lung cancer cell lines harboring EGFR T790M mutation by CRISPR/Cas9-mediated genome editing.Oncotarget2017822363313633810.18632/oncotarget.1675228422737
     [Google Scholar]
  46. Norouzi-BaroughL. SarookhaniM. SalehiR. SharifiM. MoghbelinejadS. CRISPR/Cas9, a new approach to successful knockdown of ABCB1/P-glycoprotein and reversal of chemosensitivity in human epithelial ovarian cancer cell line.Iran J Basic Med Sci201821218118729456815
     [Google Scholar]
  47. BressanR.B. DewariP.S. KalantzakiM. GangosoE. MatjusaitisM. Garcia-DiazC. BlinC. GrantV. BulstrodeH. GogolokS. SkarnesW.C. PollardS.M. Efficient CRISPR/Cas9-assisted gene targeting enables rapid and precise genetic manipulation of mammalian neural stem cells.Development2017144463564810.1242/dev.14085528096221
     [Google Scholar]
  48. RaynerE. DurinM.A. ThomasR. MoralliD. O’CathailS.M. TomlinsonI. GreenC.M. LewisA. CRISPR-Cas9 causes chromosomal instability and rearrangements in cancer cell lines, detectable by cytogenetic methods.CRISPR J20192640641610.1089/crispr.2019.000631742432
     [Google Scholar]
  49. ChenF ZhangK WangM HeZ YuB WangX VEGF-FGF signaling activates quiescent cd63+ liver stem cells to proliferate and differentiate.Adv Sci20241133e230871110.1002/advs.20230871138881531PMC11434209
     [Google Scholar]
  50. GuoC. MaX. GaoF. GuoY. Off-target effects in CRISPR/Cas9 gene editing.Front Bioeng Biotechnol202311114315710.3389/fbioe.2023.114315736970624
     [Google Scholar]
  51. LiberalF.D.C.G. McMahonS.J. Characterization of intrinsic radiation sensitivity in a diverse panel of normal, cancerous and crispr- modified cell lines.Int J Mol Sci2023249786110.3390/ijms2409786137175568
     [Google Scholar]
  52. BaeJ. ChoiY.S. ChoG. JangS.J. The patient-derived cancer organoids: Promises and challenges as platforms for cancer discovery.Cancers2022149214410.3390/cancers1409214435565273
     [Google Scholar]
  53. BoyleW.S. TwaroskiK. WoskaE.C. TolarJ. ReinekeT.M. Molecular additives significantly enhance glycopolymer-mediated transfection of large plasmids and functional crispr-cas9 transcription activation ex vivo in primary human fibroblasts and induced pluripotent stem cells.Bioconjug Chem201930241843110.1021/acs.bioconjchem.8b0076030525482
     [Google Scholar]
  54. RamalingamP.S. PremkumarT. SundararajanV. HussainM.S. ArumugamS. Design and development of dual targeting CAR protein for the development of CAR T-cell therapy against KRAS mutated pancreatic ductal adenocarcinoma using computational approaches.Discover Oncology202415159210.1007/s12672‑024‑01455‑639453574
     [Google Scholar]
  55. CarpenterM.A. LawE.K. SerebrenikA. BrownW.L. HarrisR.S. A lentivirus-based system for Cas9/gRNA expression and subsequent removal by Cre-mediated recombination.Methods2019156798410.1016/j.ymeth.2018.12.00630578845
     [Google Scholar]
  56. LuB. Javidi-ParsijaniP. MakaniV. Mehraein-GhomiF. SarhanW.M. SunD. YooK.W. AtalaZ.P. LyuP. AtalaA. Delivering SaCas9 mRNA by lentivirus-like bionanoparticles for transient expression and efficient genome editing.Nucleic Acids Res2019478e4410.1093/nar/gkz09330759231
     [Google Scholar]
  57. MangeotP.E. RissonV. FusilF. MarnefA. LaurentE. BlinJ. MournetasV. MassouridèsE. SohierT.J.M. CorbinA. AubéF. TeixeiraM. PinsetC. SchaefferL. LegubeG. CossetF.L. VerhoeyenE. OhlmannT. RicciE.P. Genome editing in primary cells and in vivo using viral-derived Nanoblades loaded with Cas9-sgRNA ribonucleoproteins.Nat Commun20191014510.1038/s41467‑018‑07845‑z30604748
     [Google Scholar]
  58. MaqboolM. HussainM.S. ShaikhN.K. SultanaA. BishtA.S. AgrawalM. Noncoding RNAs in the COVID-19 Saga: An Untold Story.Viral Immunol202437626928610.1089/vim.2024.002638968365
     [Google Scholar]
  59. MadiganV. ZhangF. DahlmanJ.E. Drug delivery systems for CRISPR-based genome editors.Nat Rev Drug Discov2023221187589410.1038/s41573‑023‑00762‑x37723222
     [Google Scholar]
  60. LiY. YangC. LiuZ. DuS. CanS. ZhangH. ZhangL. HuangX. XiaoZ. LiX. FangJ. QinW. SunC. WangC. ChenJ. ChenH. Integrative analysis of CRISPR screening data uncovers new opportunities for optimizing cancer immunotherapy.Mol Cancer2022211210.1186/s12943‑021‑01462‑z34980132
     [Google Scholar]
  61. ZhangY. LiuC. ChenX. ZhangY. LiY. HuX. Effects of web-based acceptance and commitment therapy on health-related outcomes among patients with lung cancer: A feasibility randomized controlled trial.Psychooncology20243312e7004510.1002/pon.7004539681977
     [Google Scholar]
  62. ZhuZ. ShenJ. HoP.C.L. HuY. MaZ. WangL. Transforming cancer treatment: Integrating patient-derived organoids and CRISPR screening for precision medicine.Front Pharmacol202516156319810.3389/fphar.2025.156319840201690
     [Google Scholar]
  63. LiS. LingS. WangD. WangX. HaoF. YinL. YuanZ. LiuL. ZhangL. LiY. ChenY. LuoL. DaiY. ZhangL. ChenL. DengD. TangW. ZhangS. WangS. CaiY. Modified lentiviral globin gene therapy for pediatric β/β transfusion-dependent β-thalassemia: A single-center, single-arm pilot trial.Cell Stem Cell2024317961973.e810.1016/j.stem.2024.04.02138759653
     [Google Scholar]
  64. YinM. FengC. YuZ. ZhangY. LiY. WangX. SongC. GuoM. LiC. sc2GWAS: A comprehensive platform linking single cell and GWAS traits of human.Nucleic Acids Res202553D1D1151D116110.1093/nar/gkae100839565208
     [Google Scholar]
/content/journals/cpd/10.2174/0113816128413220250728182852
Loading
CRISPR-Edited Cell Lines: A New Era in Functional Oncology Research
Curr. Pharm. Des. 32, 1027 (2026); https://doi.org/10.2174/0113816128413220250728182852
/content/journals/cpd/10.2174/0113816128413220250728182852
/content/journals/cpd/10.2174/0113816128413220250728182852
Loading

Data & Media loading...


  • Article Type:     Review Article
Keyword(s): Cancer cell lines; CRISPR/Cas9; drug resistance; gene editing; precision oncology; tumor progression

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test