CRISPR/Cas9 Technology Providing the Therapeutic Landscape of Metastatic Prostate Cancer

Overview

Journal Pharmaceuticals (Basel)

Publisher MDPI

Specialty Chemistry

Date 2025 Jan 8

PMID 39770431

Authors

Jieun Park

Jaehong Kim

Affiliations

Soon will be listed here.

Abstract

Prostate cancer (PCa) is the most prevalent malignancy and the second leading cause of cancer-related death in men. Although current therapies can effectively manage the primary tumor, most patients with late-stage disease manifest with metastasis in different organs. From surgery to treatment intensification (TI), several combinations of therapies are administered to improve the prognosis of patients with metastatic PCa. Due to the high frequency of the mutation during the metastatic phase, the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated nuclease 9 (Cas9) genetic engineering tool can accelerate the effects of TI by enhancing targeted gene therapy or immunotherapy. This review describes the genetic background of metastatic PCa and how CRISPR/Cas9 technology can contribute to the field of PCa treatment development. It also discusses the current limitations of conventional PCa therapy and the potential of CRISPR-based PCa therapy.

References

Li T, Li D, Sha J, Sun P, Huang Y . MicroRNA-21 directly targets MARCKS and promotes apoptosis resistance and invasion in prostate cancer cells. Biochem Biophys Res Commun. 2009; 383(3):280-5. DOI: 10.1016/j.bbrc.2009.03.077. View

Maitland N, Collins A . Prostate cancer stem cells: a new target for therapy. J Clin Oncol. 2008; 26(17):2862-70. DOI: 10.1200/JCO.2007.15.1472. View

Abdelaal A, Sohal I, Iyer S, Sudarshan K, Orellana E, Ozcan K . Selective targeting of chemically modified miR-34a to prostate cancer using a small molecule ligand and an endosomal escape agent. Mol Ther Nucleic Acids. 2024; 35(2):102193. PMC: 11091501. DOI: 10.1016/j.omtn.2024.102193. View

Lau W, Weber K, Doucet M, Chou Y, Brady K, Kowalski J . Identification of prospective factors promoting osteotropism in breast cancer: a potential role for CITED2. Int J Cancer. 2009; 126(4):876-84. DOI: 10.1002/ijc.24780. View

Alumkal J, Sun D, Lu E, Beer T, Thomas G, Latour E . Transcriptional profiling identifies an androgen receptor activity-low, stemness program associated with enzalutamide resistance. Proc Natl Acad Sci U S A. 2020; 117(22):12315-12323. PMC: 7275746. DOI: 10.1073/pnas.1922207117. View

Kobayashi A, Okuda H, Xing F, Pandey P, Watabe M, Hirota S . Bone morphogenetic protein 7 in dormancy and metastasis of prostate cancer stem-like cells in bone. J Exp Med. 2011; 208(13):2641-55. PMC: 3244043. DOI: 10.1084/jem.20110840. View

Robinson D, Van Allen E, Wu Y, Schultz N, Lonigro R, Mosquera J . Integrative clinical genomics of advanced prostate cancer. Cell. 2015; 161(5):1215-1228. PMC: 4484602. DOI: 10.1016/j.cell.2015.05.001. View

Liu C, Kelnar K, Liu B, Chen X, Calhoun-Davis T, Li H . The microRNA miR-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44. Nat Med. 2011; 17(2):211-5. PMC: 3076220. DOI: 10.1038/nm.2284. View

Tsujino T, Takai T, Hinohara K, Gui F, Tsutsumi T, Bai X . CRISPR screens reveal genetic determinants of PARP inhibitor sensitivity and resistance in prostate cancer. Nat Commun. 2023; 14(1):252. PMC: 9845315. DOI: 10.1038/s41467-023-35880-y. View

10.

Camargo J, Viana N, Pimenta R, Guimaraes V, Santos G, Candido P . The Effect of Gene Editing by CRISPR-Cas9 of miR-21 and the Indirect Target MMP9 in Metastatic Prostate Cancer. Int J Mol Sci. 2023; 24(19). PMC: 10573678. DOI: 10.3390/ijms241914847. View

11.

Ding Y, Li N, Dong B, Guo W, Wei H, Chen Q . Chromatin remodeling ATPase BRG1 and PTEN are synthetic lethal in prostate cancer. J Clin Invest. 2018; 129(2):759-773. PMC: 6355211. DOI: 10.1172/JCI123557. View

12.

Hussain M, Mateo J, Fizazi K, Saad F, Shore N, Sandhu S . Survival with Olaparib in Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2020; 383(24):2345-2357. DOI: 10.1056/NEJMoa2022485. View

13.

Quigley D, Dang H, Zhao S, Lloyd P, Aggarwal R, Alumkal J . Genomic Hallmarks and Structural Variation in Metastatic Prostate Cancer. Cell. 2018; 174(3):758-769.e9. PMC: 6425931. DOI: 10.1016/j.cell.2018.06.039. View

14.

Nishimura H, Minato N, Nakano T, Honjo T . Immunological studies on PD-1 deficient mice: implication of PD-1 as a negative regulator for B cell responses. Int Immunol. 1998; 10(10):1563-72. DOI: 10.1093/intimm/10.10.1563. View

15.

Vaday G, Hua S, Peehl D, Pauling M, Lin Y, Zhu L . CXCR4 and CXCL12 (SDF-1) in prostate cancer: inhibitory effects of human single chain Fv antibodies. Clin Cancer Res. 2004; 10(16):5630-9. DOI: 10.1158/1078-0432.CCR-03-0633. View

16.

Lord C, Ashworth A . PARP inhibitors: Synthetic lethality in the clinic. Science. 2017; 355(6330):1152-1158. PMC: 6175050. DOI: 10.1126/science.aam7344. View

17.

Cai H, Zhang B, Ahrenfeldt J, Joseph J, Riedel M, Gao Z . CRISPR/Cas9 model of prostate cancer identifies Kmt2c deficiency as a metastatic driver by Odam/Cabs1 gene cluster expression. Nat Commun. 2024; 15(1):2088. PMC: 10920892. DOI: 10.1038/s41467-024-46370-0. View

18.

Pettersson A, Graff R, Bauer S, Pitt M, Lis R, Stack E . The TMPRSS2:ERG rearrangement, ERG expression, and prostate cancer outcomes: a cohort study and meta-analysis. Cancer Epidemiol Biomarkers Prev. 2012; 21(9):1497-509. PMC: 3671609. DOI: 10.1158/1055-9965.EPI-12-0042. View

19.

Davis I, Martin A, Stockler M, Begbie S, Chi K, Chowdhury S . Enzalutamide with Standard First-Line Therapy in Metastatic Prostate Cancer. N Engl J Med. 2019; 381(2):121-131. DOI: 10.1056/NEJMoa1903835. View

20.

Dorff T, Blanchard M, Adkins L, Luebbert L, Leggett N, Shishido S . PSCA-CAR T cell therapy in metastatic castration-resistant prostate cancer: a phase 1 trial. Nat Med. 2024; 30(6):1636-1644. PMC: 11186768. DOI: 10.1038/s41591-024-02979-8. View