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Treatment of Castration-Resistant Prostate Cancer

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Prostate Cancer

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Abstract

Castration-resistant prostate cancer (CRPC) is a major therapeutic problem. Resistance to androgen deprivation therapy occurs in many patients after initial therapeutic success. The tumor develops genetic and epigenetic mechanisms by which it successfully bypasses the effects of the applied therapy (mutation of the gene for the receptor and enzymes of androgen synthesis, splice forms of the receptor, loss of production of antitumor proteins, and/or increased the creation of proteins that stimulate the formation of tumors, etc.). As for drugs, in CRPC, we have second-generation androgen receptor antagonists such as darolutamide, followed by abiraterone, and newer options like pembrolizumab and olaparib.

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References

  1. Denmeade SR, Isaacs JT (2002) A history of prostate cancer treatment. Nat Rev Cancer 2(5):389–396. https://doi.org/10.1038/nrc801

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Adams J (1853) The case of scirrhous of the prostate gland with corresponding affliction of the lymphatic glands in the lumbar region and in the pelvis. Lancet 1:393

    Google Scholar 

  3. Zhao J, Guercio BJ, Sahasrabudhe D (2023) Current trends in chemotherapy in the treatment of metastatic prostate cancer. Cancers (Basel) 15(15):3969. https://doi.org/10.3390/cancers15153969

    Article  CAS  PubMed  Google Scholar 

  4. Huggins C, Hodges CV (1941) Studies on prostate center: the effect of castration, of estrogen and of androgen injection on serum phosphatases on adenocarcinoma of the prostate. Cancer Res 1:293–297

    CAS  Google Scholar 

  5. Rajaram P, Rivera A, Muthima K, Olveda N, Muchalski H, Chen QH (2020) Second-generation androgen receptor antagonists as hormonal therapeutics for three forms of prostate cancer. Molecules 25(10):2448. https://doi.org/10.3390/molecules25102448

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Vellky JE, Ricke WA (2020) Development and prevalence of castration-resistant prostate cancer subtypes. Neoplasia 22(11):566–575. https://doi.org/10.1016/j.neo.2020.09.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Schmid S, Omlin A, Higano C et al (2020) Activity of platinum-based chemotherapy in patients with advanced prostate cancer with and without DNA repair gene aberrations. JAMA Netw Open 3(10):e2021692. https://doi.org/10.1001/jamanetworkopen.2020.21692

    Article  PubMed  PubMed Central  Google Scholar 

  8. Lowrance W, Dreicer R, Jarrard DF et al (2023) Updates to advanced prostate cancer: AUA/SUO guideline (2023). J Urol 209(6):1082–1090. https://doi.org/10.1097/JU.0000000000003452

    Article  PubMed  Google Scholar 

  9. Haapala K, Kuukasjärvi T, Hyytinen E, Rantala I, Helin HJ, Koivisto PA (2007) Androgen receptor amplification is associated with increased cell proliferation in prostate cancer. Hum Pathol 38(3):474–478. https://doi.org/10.1016/j.humpath.2006.09.008

    Article  CAS  PubMed  Google Scholar 

  10. Merson S, Yang ZH, Brewer D et al (2014) Focal amplification of the androgen receptor gene in hormone-naive human prostate cancer. Br J Cancer 110(6):1655–1662. https://doi.org/10.1038/bjc.2014.13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Köhler A, Demir U, Kickstein E et al (2014) A hormone-dependent feedback-loop controls androgen receptor levels by limiting MID1, a novel translation enhancer and promoter of oncogenic signaling. Mol Cancer 13:146. https://doi.org/10.1186/1476-4598-13-146

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Barbieri CE, Baca SC, Lawrence MS et al (2012) Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer. Nat Genet 44(6):685–689. https://doi.org/10.1038/ng.2279

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Pejčić T, Todorović Z, Đurašević S, Popović L (2023) Mechanisms of prostate cancer cells survival and their therapeutic targeting. Int J Mol Sci 24(3):2939. https://doi.org/10.3390/ijms24032939

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Chmelar R, Buchanan G, Need EF, Tilley W, Greenberg NM (2007) Androgen receptor coregulators and their involvement in the development and progression of prostate cancer. Int J Cancer 120(4):719–733. https://doi.org/10.1002/ijc.22365

    Article  CAS  PubMed  Google Scholar 

  15. Burd CJ, Morey LM, Knudsen KE (2006) Androgen receptor corepressors and prostate cancer. Endocr Relat Cancer 13(4):979–994. https://doi.org/10.1677/erc.1.01115

    Article  CAS  PubMed  Google Scholar 

  16. Chen EJ, Sowalsky AG, Gao S et al (2015) Abiraterone treatment in castration-resistant prostate cancer selects for progesterone responsive mutant androgen receptors. Clin Cancer Res 21(6):1273–1280. https://doi.org/10.1158/1078-0432.CCR-14-1220

    Article  CAS  PubMed  Google Scholar 

  17. Sobhani N, Neeli PK, D’Angelo A (2021) AR-V7 in metastatic prostate cancer: a strategy beyond redemption. Int J Mol Sci 22(11):5515. https://doi.org/10.3390/ijms22115515

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Hörnberg E, Ylitalo EB, Crnalic S et al (2011) Expression of androgen receptor splice variants in prostate cancer bone metastases is associated with castration-resistance and short survival. PLoS One 6(4):e19059. https://doi.org/10.1371/journal.pone.0019059

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Liu YF, Fu SQ, Yan YC et al (2021) Progress in clinical research on gonadotropin-releasing hormone receptor antagonists for the treatment of prostate cancer. Drug Des Devel Ther 15:639–649. https://doi.org/10.2147/DDDT.S291369

    Article  PubMed  PubMed Central  Google Scholar 

  20. Alyamani M, Li Z, Berk M et al (2017) Steroidogenic metabolism of Galeterone reveals a diversity of biochemical activities. Cell Chem Biol 24(7):825–832.e6. https://doi.org/10.1016/j.chembiol.2017.05.020

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Zurth C, Koskinen M, Fricke R et al (2019) Drug-drug interaction potential of darolutamide: in vitro and clinical studies. Eur J Drug Metab Pharmacokinet 44(6):747–759. https://doi.org/10.1007/s13318-019-00577-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Maurice-Dror C, Le Moigne R, Vaishampayan U et al (2022) A phase 1 study to assess the safety, pharmacokinetics, and anti-tumor activity of the androgen receptor n-terminal domain inhibitor epi-506 in patients with metastatic castration-resistant prostate cancer. Investig New Drugs 40(2):322–329. https://doi.org/10.1007/s10637-021-01202-6

    Article  CAS  Google Scholar 

  23. Eastham JA, Auffenberg GB, Barocas DA et al (2022) Clinically localized prostate cancer: AUA/ASTRO guideline, part II: principles of active surveillance, principles of surgery, and follow-up. J Urol 208(1):19–25. https://doi.org/10.1097/JU.0000000000002758

    Article  PubMed  Google Scholar 

  24. Antonarakis ES, Piulats JM, Gross-Goupil M et al (2020) Pembrolizumab for treatment-refractory metastatic castration-resistant prostate cancer: multicohort, open-label phase II KEYNOTE-199 study. J Clin Oncol 38(5):395–405. https://doi.org/10.1200/JCO.19.01638

    Article  CAS  PubMed  Google Scholar 

  25. Tisseverasinghe S, Bahoric B, Anidjar M, Probst S, Niazi T (2023) Advances in PARP inhibitors for prostate cancer. Cancers (Basel) 15(6):1849. https://doi.org/10.3390/cancers15061849

    Article  CAS  PubMed  Google Scholar 

  26. Radulovic S, Bjelogrlic S, Todorovic Z, Prostran M (2006) Chemosensitisation by poly(ADP-ribose) polymerase-1 (PARP-1) inhibitor 5-aminoisoquinoline (5-AIQ) on various melanoma cell lines. J Clin Oncol 24:12019

    Article  Google Scholar 

  27. Todorović Z, Đurašević S, Stojković M et al (2021) Lipidomics provides new insight into pathogenesis and therapeutic targets of the ischemia-reperfusion injury. Int J Mol Sci 22(6):2798. https://doi.org/10.3390/ijms22062798

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Saad F, Clarke NW, Oya M et al (2023) Olaparib plus abiraterone versus placebo plus abiraterone in metastatic castration-resistant prostate cancer (PROpel): final prespecified overall survival results of a randomised, double-blind, phase 3 trial. Lancet Oncol 24(10):1094–1108. https://doi.org/10.1016/S1470-2045(23)00382-0

    Article  CAS  PubMed  Google Scholar 

  29. Nyquist MD, Corella A, Coleman I et al (2020) Combined TP53 and RB1 loss promotes prostate cancer resistance to a spectrum of therapeutics and confers vulnerability to replication stress. Cell Rep 31(8):107669. https://doi.org/10.1016/j.celrep.2020.107669

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Author information

Authors and Affiliations

  1. Faculty of Medicine, University of Belgrade, Belgrade, Serbia

    Zoran Todorović

  2. University Clinical Hospital Center Bezanijska Kosa, Belgrade, Serbia

    Zoran Todorović

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  1. Zoran Todorović
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Editors and Affiliations

  1. Department of Biochemistry, Medical Faculty University of Nis, Nis, Serbia

    Gordana Kocic

  2. Serbian Academy of Science and Arts, Belgrade, Serbia

    Jovan Hadzi-Djokic

  3. Faculty of Medicine, University of Belgrade, Belgrade, Serbia

    Tatjana Simic

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© 2024 The Author(s), under exclusive license to Springer Nature Switzerland AG

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Todorović, Z. (2024). Treatment of Castration-Resistant Prostate Cancer. In: Kocic, G., Hadzi-Djokic, J., Simic, T. (eds) Prostate Cancer. Springer, Cham. https://doi.org/10.1007/978-3-031-51712-9_19

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