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Recent advances in the molecular targeted drugs for prostate cancer

  • Urology - Review
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Abstract

Context

Prostate cancer (PCa) is the second largest male tumor in the world and one of the most common malignant tumors in the urinary system. In recent years, the incidence rate of PCa in China has been increasing year by year. Meanwhile, refractory hormone resistance and adverse drug reactions of advanced PCa cause serious harm to patients.

Objective

The present study aims to systematically review the recent advances in molecularly targeted drugs for prostate cancer and to use the retrieval and analysis of the literature library to summarize the adverse effects of different drugs so as to maximize the treatment benefits of targeted therapies.

Evidence acquisition

We performed a systematic literature search of the Medline, EMBASE, PubMed, and Cochrane databases up to March 2022 in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Medical Subject Heading (MeSH) terms and keywords such as (prostate cancer) AND (molecular target drugs) AND (side effect) were used. No language restrictions were set on the search process, and all these results were processed independently by two authors. Consensus was reached through discussion once met with any disagreements. The primary endpoint was differential features between different molecular targeted drugs. Secondary endpoints were side effects of different drugs on the body and corresponding prognostic values.

Evidence synthesis

The Cochrane Collaboration risk of bias tool was used to assess the study quality in terms of sequence generation, allocation concealment, blinding, the completeness of outcome data, selective reporting and other biases. We retrieved 332 articles, of which 49 met the criteria for inclusion. Included studies show that prostatic tumor cells, tumor neovascularization and immune checkpoints are the main means for targeted therapy. Common drugs include 177 Lu-PSMA, Olaparib, Rucaparib, Bevacizumab, Pazopanib, Sorafenib, Cabozantinib, Aflibercept, Ipilimumab, Atezolizumab, Avelumab, Durvalumab. A series of publicly available data suitable for further analysis of side effects. An over-representation analysis of these datasets revealed reasonable dosage and usage is the key to controlling the side effects of targeted drugs. Important information such as the publication year, the first author, location and outcome observation of adverse effects was extracted from the original article. If the study data has some insufficient data, contacting the corresponding authors is necessary. All the studies included prospective nonrandomized and randomized research. Retrospective reviews were also screened according to the relevant to the purpose of this study. Meeting abstracts as well as letters to the editor and editorials were excluded.

Statistical analysis

Data analysis was based on Cochrane's risk of bias tools to obtain the quality assessment. The included randomized studies used RoB2 and non-randomized ones corresponded to ROBINS-I. Standardized mean differences (SMD) were used to determine relative risk (RR) and side effects between groups. The eggers’ test was used to check the publication bias from variable information in the included studies. All p < 0.05 were considered to be significant, and 95% was set as the confidence interval.

Conclusions

With the approval of a variety of targeted drugs, targeted therapy will be widely used in the treatment of advanced or metastatic prostate cancer. Despite the existence of adverse reactions related to targeted drug treatment, it is still meaningful to adjust the drug dosage or treatment cycle to reduce the occurrence of adverse reactions, improving the treatment benefits of patients.

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Data availability

Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.

References

  1. Rawla P (2019) Epidemiology of prostate cancer. World j oncol 10(2):63

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Ilic D, Neuberger MM, Djulbegovic M, Dahm P (2013) Screening for prostate cancer. Cochrane data syst reviews. https://doi.org/10.1002/14651858.CD004720.pub3

    Article  Google Scholar 

  3. Feng RM, Zong YN, Cao SM, Xu RH (2019) Current cancer situation in China: good or bad news from the 2018 Global Cancer Statistics? Cancer Commun 39(1):1–12

    Article  CAS  Google Scholar 

  4. Litwin MS, Tan H-J (2017) The diagnosis and treatment of prostate cancer: a review. JAMA 317(24):2532–2542

    Article  PubMed  Google Scholar 

  5. Saad F, Cella D, Basch E et al (2018) Effect of apalutamide on health-related quality of life in patients with non-metastatic castration-resistant prostate cancer: an analysis of the SPARTAN randomised, placebo-controlled, phase 3 trial. Lancet Oncol 19(10):1404–1416

    Article  CAS  PubMed  Google Scholar 

  6. Crawford ED, Heidenreich A, Lawrentschuk N et al (2019) Androgen-targeted therapy in men with prostate cancer: evolving practice and future considerations. Prostate Cancer Prostatic Dis 22(1):24–38

    Article  PubMed  Google Scholar 

  7. Slootbeek PH, Kloots IS, Smits M et al (2022) Impact of molecular tumour board discussion on targeted therapy allocation in advanced prostate cancer. Br J Cancer 126(6):907–916

    Article  CAS  PubMed  Google Scholar 

  8. Nuhn P, De Bono JS, Fizazi K et al (2019) Update on systemic prostate cancer therapies: management of metastatic castration-resistant prostate cancer in the era of precision oncology. Eur Urol 75(1):88–99

    Article  PubMed  Google Scholar 

  9. Lee YT, Tan YJ, Oon CE (2018) Molecular targeted therapy: Treating cancer with specificity. Eur J Pharmacol 834:188–196

    Article  CAS  PubMed  Google Scholar 

  10. Hutson TE (2011) Targeted therapies for the treatment of metastatic renal cell carcinoma: clinical evidence. Oncologist 16(S2):14–22

    Article  PubMed  PubMed Central  Google Scholar 

  11. Arsenault F, Beauregard J-M, Pouliot F (2018) Prostate-specific membrane antigen for prostate cancer theranostics: from imaging to targeted therapy. Curr Opin Support Palliat Care 12(3):359–365

    Article  PubMed  Google Scholar 

  12. Feldmann A, Arndt C, Bergmann R et al (2017) Retargeting of T lymphocytes to PSCA-or PSMA positive prostate cancer cells using the novel modular chimeric antigen receptor platform technology “UniCAR.” Oncotarget 8(19):31368

    Article  PubMed  PubMed Central  Google Scholar 

  13. Bravaccini S, Puccetti M, Bocchini M et al (2018) PSMA expression: a potential ally for the pathologist in prostate cancer diagnosis. Sci Rep 8(1):1–8

    Article  CAS  Google Scholar 

  14. Bernacki KD, Fields KL, Roh MH (2014) The utility of PSMA and PSA immunohistochemistry in the cytologic diagnosis of metastatic prostate carcinoma. Diagn Cytopathol 42(7):570–575

    Article  PubMed  Google Scholar 

  15. Hofman MS, Violet J, Hicks RJ et al (2018) [177Lu]-PSMA-617 radionuclide treatment in patients with metastatic castration-resistant prostate cancer (LuPSMA trial): a single-centre, single-arm, phase 2 study. Lancet Oncol 19(6):825–833

    Article  CAS  PubMed  Google Scholar 

  16. Yadav MP, Ballal S, Sahoo RK, Dwivedi SN, Bal C (2019) Radioligand therapy with 177Lu-PSMA for metastatic castration-resistant prostate cancer: a systematic review and meta-analysis. Am J Roentgenol 213(2):275–285

    Article  Google Scholar 

  17. Seifert R, Kessel K, Schlack K et al (2021) PSMA PET total tumor volume predicts outcome of patients with advanced prostate cancer receiving [177Lu] Lu-PSMA-617 radioligand therapy in a bicentric analysis. Eur J Nucl Med Mol Image 48(4):1200–1210

    Article  CAS  Google Scholar 

  18. Sartor O, De Bono J, Chi KN et al (2021) Lutetium-177–PSMA-617 for metastatic castration-resistant prostate cancer. N Engl J Med 385(12):1091–1103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Olson WC, Israel RJ (2014) Antibody-drug conjugates targeting prostate-specific membrane antigen. Front Biosci-Land 19(1):12–33

    Article  Google Scholar 

  20. Lin P, Davis I, Chua W et al (2021) [(177) Lu] Lu-PSMA-617 versus cabazitaxel in patients with metastatic castration-resistant prostate cancer (TheraP): a randomised, open-label, phase 2 trial. Lancet 44:665

    Google Scholar 

  21. Minchom A, Aversa C, Lopez J (2018) Dancing with the DNA damage response: next-generation anti-cancer therapeutic strategies. Therapeutic advances in medical oncology 10:1758835918786658

    Article  PubMed  PubMed Central  Google Scholar 

  22. Lang SH, Swift SL, White H, Misso K, Kleijnen J, Quek RG (2019) A systematic review of the prevalence of DNA damage response gene mutations in prostate cancer. Int J Oncol 55(3):597–616

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Taylor RA, Fraser M, Rebello RJ et al (2019) The influence of BRCA2 mutation on localized prostate cancer. Nat Rev Urol 16(5):281–290

    Article  PubMed  Google Scholar 

  24. Antonarakis ES, Gomella LG, Petrylak DP (2020) When and how to use PARP inhibitors in prostate cancer: a systematic review of the literature with an update on on-going trials. Euro urol oncol 3(5):594–611

    Article  Google Scholar 

  25. Hussain M, Mateo J, Fizazi K et al (2019) PROfound: Phase III study of olaparib versus enzalutamide or abiraterone for metastatic castration-resistant prostate cancer (mCRPC) with homologous recombination repair (HRR) gene alterations. Ann Oncol 30:v881–v882

    Article  Google Scholar 

  26. Rao A, Moka N, Hamstra DA, Ryan CJ (2022) Co-inhibition of androgen receptor and parp as a novel treatment paradigm in prostate cancer—where are we now? Cancers 14(3):801

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Schaeffer E, Srinivas S, Antonarakis ES et al (2021) NCCN guidelines insights: Prostate cancer, version 1 2021: Featured updates to the NCCN guidelines. J National Comp Cancer Net. 19(2):134–143

    Article  CAS  Google Scholar 

  28. Egevad L, Delahunt B, Srigley JR, Samaratunga H (2016) International Society of Urological Pathology (ISUP) grading of prostate cancer–An ISUP consensus on contemporary grading. Wiley Online Lib. 124:433–435

    Google Scholar 

  29. Canete-Portillo S, Velazquez EF, Kristiansen G, et al. 2020 Report from the International Society of Urological Pathology (ISUP) Consultation Conference on Molecular Pathology of Urogenital Cancers V Recommendations on the use of and molecular biomarkers in penile cancer. Amer J Surg Pathol. 44: 88

  30. Pacey S, Linch MD, Kynaston H et al (2019) A study into the pharmacodynamic biomarker effects of olaparib (PARP Inhibitor)±degarelix (GnRH antagonist) given prior to radical prostatectomy (RP) CANCAP03. Amer Soc Clin Oncol. https://doi.org/10.1200/JCO.2019.37.7_suppl.35

    Article  Google Scholar 

  31. Labadie BW, Morris DS, Bryce AH et al (2022) Guidelines for Management of Treatment-Emergent Adverse Events During Rucaparib Treatment of Patients with Metastatic Castration-Resistant Prostate Cancer. Cancer Management Res 14:673

    Article  CAS  Google Scholar 

  32. Aggarwal R, Huang J, Alumkal JJ et al (2018) Clinical and genomic characterization of treatment-emergent small-cell neuroendocrine prostate cancer: a multi-institutional prospective study. J Clin Oncol 36(24):2492

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Zhang X, Hu Q, Chen Y et al (2017) PSCA rs1045531 polymorphism and the risk of prostate cancer in a Chinese population undergoing prostate biopsy. Technol Cancer Res Treat 16(6):1168–1172

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Zhao Z, Li E, Luo L et al (2020) A PSCA/PGRN–NF-κB–Integrin–α4 Axis promotes prostate cancer cell adhesion to bone marrow endothelium and enhances metastatic potentialpsca/pgrn promotes prostate cancer bone metastasis. Mol Cancer Res 18(3):501–513

    Article  CAS  PubMed  Google Scholar 

  35. Farahani MS, Saraygord-Afshari N, Farajollahi MM (2021) Optimizing the preparation procedure of recombinant psca, as a practical biomarker in prostate cancer. Iran J Biotechnol 19(2):e2631

    Google Scholar 

  36. Yu S, Feng F, Wang K et al (2013) The therapeutic efficacy of I131-PSCA-mAb in orthotopic mouse models of prostate cancer. Eur J Med Res 18(1):1–7

    Article  Google Scholar 

  37. Benko A, Medina-Cruz D, Vernet-Crua A et al (2021) Nanocarrier drug resistant tumor interactions: Novel approaches to fight drug resistance in cancer. Cancer Drug Resist 4(2):264

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Jamaspishvili T, Berman DM, Ross AE et al (2018) Clinical implications of PTEN loss in prostate cancer. Nat Rev Urol 15(4):222–234

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Zhang S, Yu J, Sun B-f, Hou G-z, Yu Z-J, Luo H (2020) MicroRNA-92a targets SERTAD3 and regulates the growth, invasion, and migration of prostate cancer cells via the P53 pathway. OncoTargets therapy. 13:5495

    Article  PubMed  PubMed Central  Google Scholar 

  40. Huang H, Qing XY, Zhou Q, Li HD, Hu ZY (2021) Silencing of microRNA-3175 represses cell proliferation and invasion in prostate cancer by targeting the potential tumor-suppressor SCN4B. Kaohsiung J Med Sci 37(1):20–26

    Article  CAS  PubMed  Google Scholar 

  41. Niemira M, Borowa-Mazgaj B, Bader SB et al (2020) Anticancer imidazoacridinone C-1311 is effective in androgen-dependent and androgen-independent prostate cancer cells. Biomedicines 8(9):292

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Genovesi S, Moro R, Vignoli B et al (2022) Trpm8 Expression in Human and Mouse Castration Resistant Prostate Adenocarcinoma Paves the Way for the Preclinical Development of TRPM8-Based Targeted Therapies. Biomolecules 12(2):193

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Alaimo A, Lorenzoni M, Ambrosino P et al (2020) Calcium cytotoxicity sensitizes prostate cancer cells to standard-of-care treatments for locally advanced tumors. Cell Death Dis 11(12):1–17

    Article  Google Scholar 

  44. Azzouzi A-R, Vincendeau S, Barret E et al (2017) Padeliporfin vascular-targeted photodynamic therapy versus active surveillance in men with low-risk prostate cancer (CLIN1001 PCM301): an open-label, phase 3, randomised controlled trial. Lancet Oncol 18(2):181–191

    Article  CAS  PubMed  Google Scholar 

  45. Karaki S, Benizri S, Mejías R et al (2017) Lipid-oligonucleotide conjugates improve cellular uptake and efficiency of TCTP-antisense in castration-resistant prostate cancer. J Control Release 258:1–9

    Article  CAS  PubMed  Google Scholar 

  46. Wang Y, Alahdal M, Ye J et al (2019) Inhibition of RM-1 prostate carcinoma and eliciting robust immune responses in the mouse model by using VEGF-M2-GnRH3-hinge-MVP vaccine. Genes Immun 20(3):245–254

    Article  PubMed  Google Scholar 

  47. Itatani Y, Kawada K, Yamamoto T, Sakai Y (2018) Resistance to anti-angiogenic therapy in cancer—alterations to anti-VEGF pathway. Int J Mol Sci 19(4):1232

    Article  PubMed  PubMed Central  Google Scholar 

  48. Sun S, Gong F, Liu P, Miao Q (2018) Metformin combined with quercetin synergistically repressed prostate cancer cells via inhibition of VEGF/PI3K/Akt signaling pathway. Gene 664:50–57

    Article  CAS  PubMed  Google Scholar 

  49. Zou W, Tang Z, Long Y, Xiao Z, Ouyang B, Liu M (2021) Kochiae fructus, the fruit of common potherb Kochia scoparia (L.) Schrad: a review on phytochemistry, pharmacology, toxicology, quality control, and pharmacokinetics. Evidence-Based Complement Alter Med. 2021:1–17

    Google Scholar 

  50. Cereda V, Formica V, Roselli M (2018) Issues and promises of bevacizumab in prostate cancer treatment. Expert Opin Biol Ther 18(6):707–717

    Article  CAS  PubMed  Google Scholar 

  51. Hussain M, Rathkopf DE, Liu G et al (2012) A phase II randomized study of cixutumumab (IMC-A12: CIX) or ramucirumab (IMC‐1121B: RAM) plus mitoxantrone (M) and prednisone (P) in patients (pts) with metastatic castrate-resistant prostate cancer (mCRPC) following disease progression (PD) on docetaxel (DCT) therapy. J Clin Oncol 30:97–97

    Article  Google Scholar 

  52. Sridhar SS, Joshua AM, Gregg R et al (2015) A phase II study of GW786034 (pazopanib) with or without bicalutamide in patients with castration-resistant prostate cancer. Clin Genitourin Cancer 13(2):124–129

    Article  PubMed  Google Scholar 

  53. GuneyEskiler G, Deveci AO, Bilir C, Kaleli S (2019) Synergistic effects of nobiletin and sorafenib combination on metastatic prostate cancer cells. Nutr Cancer 71(8):1299–1312

    Article  CAS  Google Scholar 

  54. Smith M, De Bono J, Sternberg C et al (2016) Phase III study of cabozantinib in previously treated metastatic castration-resistant prostate cancer: COMET-1. J Clin Oncol 34(25):3005–3013

    Article  CAS  PubMed  Google Scholar 

  55. Tannock IF, Fizazi K, Ivanov S et al (2013) Aflibercept versus placebo in combination with docetaxel and prednisone for treatment of men with metastatic castration-resistant prostate cancer (VENICE): a phase 3, double-blind randomised trial. Lancet Oncol 14(8):760–768

    Article  CAS  PubMed  Google Scholar 

  56. Papadopoulos N, Lennartsson J (2018) The PDGF/PDGFR pathway as a drug target. Mol Aspects Med 62:75–88

    Article  CAS  PubMed  Google Scholar 

  57. Sun D-Y, Wu J-Q, He Z-H, He M-F, Sun H-B (2019) Cancer-associated fibroblast regulate proliferation and migration of prostate cancer cells through TGF-β signaling pathway. Life Sci 235:116791

    Article  CAS  PubMed  Google Scholar 

  58. Fischer A, Wolf I, Fuchs H, Masilamani AP, Wolf P (2020) Pseudomonas exotoxin A based toxins targeting epidermal growth factor receptor for the treatment of prostate cancer. Toxins 12(12):753

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Tapia JC, Niechi I (2019) Endothelin-converting enzyme-1 in cancer aggressiveness. Cancer Lett 452:152–157

    Article  CAS  PubMed  Google Scholar 

  60. Zhang X (2019) Interactions between cancer cells and bone microenvironment promote bone metastasis in prostate cancer. Cancer Commun 39(1):1–10

    Article  Google Scholar 

  61. Sugawara T, NGuyen H, Corey E, et al (2022) Combination of the androgen receptor inhibitor darolutamide and the PI3K inhibitor copanlisib leads to improved anti-tumor efficacy and apoptosis in prostate cancer models. Cancer Res 82:651–651

    Article  Google Scholar 

  62. Elgendy M, Ciro M, Hosseini A et al (2019) Combination of hypoglycemia and metformin impairs tumor metabolic plasticity and growth by modulating the PP2A-GSK3β-MCL-1 axis. Cancer Cell 35(5):798–815

    Article  CAS  PubMed  Google Scholar 

  63. Venkatachalam S, McFarland TR, Agarwal N, Swami U (2021) Immune checkpoint inhibitors in prostate cancer. Cancers 13(9):2187

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Shin MH, Kim J, Lim SA, Kim J, Lee K-M (2020) Current insights into combination therapies with MAPK inhibitors and immune checkpoint blockade. Int J Mol Sci 21(7):2531

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Huff WX, Kwon JH, Henriquez M, Fetcko K, Dey M (2019) The evolving role of CD8+ CD28− immunosenescent T cells in cancer immunology. Int J Mol Sci 20(11):2810

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Hoekstra ME, Bornes L, Dijkgraaf FE et al (2020) Long-distance modulation of bystander tumor cells by CD8+ T-cell-secreted IFN-γ. Nature Cancer 1(3):291–301

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Hofman MS, Emmett L, Sandhu SK et al (2021) 177Lu-PSMA-617 (LuPSMA) versus cabazitaxel in metastatic castration-resistant prostate cancer (mCRPC) progressing after docetaxel: Updated results including progression-free survival (PFS) and patient-reported outcomes (PROs)(TheraP ANZUP 1603). Amer Soc Clinical Oncol. https://doi.org/10.1200/JCO.2021.39.6_suppl.6

    Article  Google Scholar 

  68. Mansfield AS, Park SS, Dong H (2015) Synergy of cancer immunotherapy and radiotherapy. Aging (Albany NY) 7(3):144

    Article  CAS  PubMed  Google Scholar 

  69. Sweeney CJ, Gillessen S, Rathkopf D et al (2020) Abstract CT014: IMbassador250: A phase III trial comparing atezolizumab with enzalutamide vs enzalutamide alone in patients with metastatic castration-resistant prostate cancer (mCRPC). Cancer Res 80:14–24

    Article  Google Scholar 

  70. Tucker MD, Zhu J, Marin D et al (2019) Pembrolizumab in men with heavily treated metastatic castrate-resistant prostate cancer. Cancer Med 8(10):4644–4655

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Ross AE, Hurley PJ, Tran PT et al (2020) A pilot trial of pembrolizumab plus prostatic cryotherapy for men with newly diagnosed oligometastatic hormone-sensitive prostate cancer. Prostate Cancer Prostatic Dis 23(1):184–193

    Article  CAS  PubMed  Google Scholar 

  72. Kwan EM, Spain L, Anton A et al (2022) Avelumab combined with stereotactic ablative body radiotherapy in metastatic castration-resistant prostate cancer: the phase 2 ICE-PAC clinical trial. Eur Urol 81(3):253–262

    Article  CAS  PubMed  Google Scholar 

  73. Patnaik A, Duttagupta P, Chaudagar K et al (2020) A phase Ib/IIa study of rucaparib (PARP inhibitor) combined with nivolumab in metastatic castrate-resistant prostate cancer. Amer Soc Clinical Oncol. https://doi.org/10.1200/JCO.2020.38.6_suppl.TPS270

    Article  Google Scholar 

  74. Subudhi SK, Siddiqui BA, Aparicio AM et al (2021) Combined CTLA-4 and PD-L1 blockade in patients with chemotherapy-naive metastatic castration-resistant prostate cancer is associated with increased myeloid and neutrophil immune subsets in the bone microenvironment. J immun cancer. 9(10):e002919

    Article  Google Scholar 

  75. Brown LC, Halabi S, Humeniuk MS et al (2021) Efficacy of the PD-L1 inhibitor avelumab in neuroendocrine or aggressive variant prostate cancer: Results from a phase II, single-arm study. Amer Soc Clin Oncol. 39:89

    Article  Google Scholar 

  76. Lampert EJ, Zimmer A, Padget M et al (2020) Combination of PARP inhibitor olaparib, and pd-l1 inhibitor durvalumab, in recurrent ovarian cancer: a proof-of-concept phase ii studyphase ii study of olaparib with durvalumab in ovarian cancer. Clin Cancer Res 26(16):4268–4279

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Powles T, Yuen KC, Gillessen S et al (2022) Atezolizumab with enzalutamide versus enzalutamide alone in metastatic castration-resistant prostate cancer: A randomized phase 3 trial. Nat Med 28(1):144–153

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Kontos F, Michelakos T, Kurokawa T et al (2021) B7–H3: An attractive target for antibody-based immunotherapyb7-h3: an attractive target for antibody-based immunotherapy. Clin Cancer Res 27(5):1227–1235

    Article  CAS  PubMed  Google Scholar 

  79. Lucarelli G, Loizzo D, Ferro M et al (2019) Metabolomic profiling for the identification of novel diagnostic markers and therapeutic targets in prostate cancer: An update. Expert Rev Mol Diagn 19(5):377–387

    Article  CAS  PubMed  Google Scholar 

  80. Lucarelli G, Rutigliano M, Galleggiante V et al (2015) Metabolomic profiling for the identification of novel diagnostic markers in prostate cancer. Expert Rev Mol Diagn 15(9):1211–1224

    Article  CAS  PubMed  Google Scholar 

  81. Grossi V, Lucarelli G, Forte G et al (2015) Loss of STK11 expression is an early event in prostate carcinogenesis and predicts therapeutic response to targeted therapy against MAPK/p38. Autophagy 11:2102

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Loizzo D, Pandolfo SD, Rogers D et al (2022) Novel insights into autophagy and prostate cancer: a comprehensive review. Int J Mol Sci 23(7):3826

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Leconet W, Liu H, Guo M et al (2018) Anti-PSMA/CD3 Bispecific Antibody Delivery and Antitumor Activity Using a Polymeric Depot FormulationPolymeric Formulation and Delivery of a Small BiTE. Mol Cancer Ther 17(9):1927–1940

    Article  CAS  PubMed  Google Scholar 

  84. Patel M, Lum LG, Deol A et al (2020) Phase II trial of a novel immunotherapy combination of pembrolizumab and HER2 bi-armed activated T cells (BATs) in metastatic castrate resistant prostate cancer. Amer Soc Clin Oncol. 38:97

    Article  Google Scholar 

  85. Boettcher AN, Usman A, Morgans A, VanderWeele DJ, Sosman J, Wu JD (2019) Past, current, and future of immunotherapies for prostate cancer. Front Oncol 9:884

    Article  PubMed  PubMed Central  Google Scholar 

  86. Thomas-Jardin SE, Dahl H, Nawas AF, Bautista M, Delk NA (2020) NF-κB signaling promotes castration-resistant prostate cancer initiation and progression. Pharmacol Ther 211:107538

    Article  CAS  PubMed  Google Scholar 

  87. Saad F, Sternberg CN, Mulders PF, Niepel D, Tombal BF (2018) The role of bisphosphonates or denosumab in light of the availability of new therapies for prostate cancer. Cancer Treat Rev 68:25–37

    Article  CAS  PubMed  Google Scholar 

  88. Iikuni S, Tarumizu Y, Nakashima K et al (2021) Radiotheranostics using a novel 225Ac-labeled radioligand with improved pharmacokinetics targeting prostate-specific membrane antigen. J Med Chem 64(18):13429–13438

    Article  CAS  PubMed  Google Scholar 

  89. Kratochwil C, Haberkorn U, Giesel FL (2020) 225Ac-PSMA-617 for therapy of prostate cancer. Elsevier 50:133–140

    Google Scholar 

  90. Ablin RJ (2011) The need for personalized therapy and companion diagnostics in prostate cancer. Biomark Med 5(3):281–283

    Article  PubMed  Google Scholar 

  91. Kim SB, Song IH, Kim SY et al (2022) Preclinical evaluation of a companion diagnostic radiopharmaceutical,[18F] PSMA-1007, in a subcutaneous prostate cancer xenograft mouse model. Mol Pharma. https://doi.org/10.1021/acs.molpharmaceut.2c00788

    Article  Google Scholar 

  92. Kim SB, Song IH, Song YS et al (2021) Biodistribution and internal radiation dosimetry of a companion diagnostic radiopharmaceutical,[68Ga] PSMA-11, in subcutaneous prostate cancer xenograft model mice. Sci Rep 11(1):1–11

    Google Scholar 

  93. Fu Z, Yuan Y (2022) The role of tumor neogenesis pipelines in tumor progression and their therapeutic potential. Cancer Med 12:1558

    Article  PubMed  PubMed Central  Google Scholar 

  94. Mazzarella L, Duso BA, Trapani D et al (2019) The evolving landscape of ‘next-generation’immune checkpoint inhibitors: A review. Eur J Cancer 117:14–31

    Article  CAS  PubMed  Google Scholar 

  95. Vanella V, Festino L, Strudel M, Simeone E, Grimaldi AM, Ascierto PA (2018) PD-L1 inhibitors in the pipeline: promise and progress. Oncoimmunology 7(1):e1365209

    Article  Google Scholar 

  96. Jakob T, Tesfamariam YM, Macherey S et al (2020) Bisphosphonates or RANK-ligand-inhibitors for men with prostate cancer and bone metastases: a network meta-analysis. Cochrane Data Systemat Reviews. https://doi.org/10.1002/14651858.CD013020.pub2

    Article  Google Scholar 

  97. Zhao H, Ma J, Lei T, Ma W, Zhang M (2019) The bispecific anti-CD3× anti-CD155 antibody mediates T cell immunotherapy for human prostate cancer. Invest New Drugs 37(5):810–817

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors thank for the help from the medical research fund of Guizhou Provincial People's Hospital and the Affiliated Hospital of Guizhou Medical University.

Funding

This work received financial support from the medical research fund of Guizhou Provincial People's Hospital and the Affiliated Hospital of Guizhou Medical University.

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GL Methodology, Writing–review & editing, Funding acquisition, Supervision TL Funding acquisition, Conceptualization. KZ Data curation, Writing–review & editing PG Methodology, Data curation, Writing–original draft.

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Correspondence to Guangheng Luo.

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Gao, P., Li, T., Zhang, K. et al. Recent advances in the molecular targeted drugs for prostate cancer. Int Urol Nephrol 55, 777–789 (2023). https://doi.org/10.1007/s11255-023-03487-3

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  • Issue Date:

  • DOI: https://doi.org/10.1007/s11255-023-03487-3

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