{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T18:36:48Z","timestamp":1792175808420,"version":"4.4.0"},"reference-count":179,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,4,27]],"date-time":"2025-04-27T00:00:00Z","timestamp":1745712000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NATIONAL CANCER CENTER","award":["2211880-3"],"award-info":[{"award-number":["2211880-3"]}]},{"name":"NATIONAL CANCER CENTER","award":["1941760-1"],"award-info":[{"award-number":["1941760-1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Metastatic prostate cancer (mPCa) remains a significant cause of cancer-related mortality in men. Advances in molecular profiling have demonstrated that the androgen receptor (AR) axis, DNA damage repair pathways, and the PI3K\/AKT\/mTOR pathway are critical drivers of disease progression and therapeutic resistance. Despite the established benefits of hormone therapy, chemotherapy, and bone-targeting agents, mPCa commonly becomes treatment-resistant. Recent breakthroughs have highlighted the importance of identifying actionable genetic alterations, such as BRCA2 or ATM defects, that render tumors sensitive to poly-ADP ribose polymerase (PARP) inhibitors. Parallel efforts have refined imaging\u2014particularly prostate-specific membrane antigen (PSMA) positron emission tomography-computed tomography\u2014to detect and localize metastatic lesions with high sensitivity, thereby guiding patient selection for PSMA-targeted radioligand therapies. Multi-omics innovations, including liquid biopsy technologies, enable the real-time tracking of emergent AR splice variants or reversion mutations, supporting adaptive therapy paradigms. Nonetheless, the complexity of mPCa necessitates combination strategies, such as pairing AR inhibition with PI3K\/AKT blockade or PARP inhibitors, to inhibit tumor plasticity. Immuno-oncological approaches remain challenging for unselected patients; however, subsets with mismatch repair deficiency or neuroendocrine phenotypes may benefit from immune checkpoint blockade or targeted epigenetic interventions. We present these pivotal advances, and discuss how biomarker-guided integrative treatments can improve mPCa management.<\/jats:p>","DOI":"10.3390\/biom15050625","type":"journal-article","created":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T08:28:11Z","timestamp":1746174491000},"page":"625","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Precision Targeting in Metastatic Prostate Cancer: Molecular Insights to Therapeutic Frontiers"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7833-5981","authenticated-orcid":false,"given":"Whi-An","family":"Kwon","sequence":"first","affiliation":[{"name":"Department of Urology, Hanyang University College of Medicine, Myongji Hospital, Goyang 10475, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae Young","family":"Joung","sequence":"additional","affiliation":[{"name":"Department of Urology, Urological Cancer Center, National Cancer Center, Goyang 10408, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.eururo.2023.04.021","article-title":"2022 Update on Prostate Cancer Epidemiology and Risk Factors-A Systematic Review","volume":"84","author":"Bergengren","year":"2023","journal-title":"Eur. Urol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Lv, Z., Wang, X., Zhu, C., and Wang, K. (2022). The global status of research in prostate cancer bone metastasis: A bibliometric and visualized analysis. Front. Med., 9.","DOI":"10.3389\/fmed.2022.931422"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Chen, H., Lyu, F., and Gao, X. (2024). Advances in ferroptosis for castration-resistant prostate cancer treatment: Novel drug targets and combination therapy strategies. Prostate Cancer Prostatic Dis.","DOI":"10.1038\/s41391-024-00933-w"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1038\/s41388-024-03036-x","article-title":"Alternative splicing in prostate cancer progression and therapeutic resistance","volume":"43","author":"Rawat","year":"2024","journal-title":"Oncogene"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Vitorino, R. (2024). Transforming Clinical Research: The Power of High-Throughput Omics Integration. Proteomes, 12.","DOI":"10.3390\/proteomes12030025"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"4341","DOI":"10.1038\/s41467-024-48629-y","article-title":"Integrative multi-region molecular profiling of primary prostate cancer in men with synchronous lymph node metastasis","volume":"15","author":"Singhal","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Taylor, A.K., Kosoff, D., Emamekhoo, H., Lang, J.M., and Kyriakopoulos, C.E. (2023). PARP inhibitors in metastatic prostate cancer. Front. Oncol., 13.","DOI":"10.3389\/fonc.2023.1159557"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"290","DOI":"10.5534\/wjmh.230177","article-title":"PARP Inhibitors in the Treatment of Prostate Cancer: From Scientific Rationale to Clinical Development","volume":"42","author":"Kwon","year":"2024","journal-title":"World J. Mens. Health"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2113","DOI":"10.1016\/j.ccell.2024.10.015","article-title":"Elucidating acquired PARP inhibitor resistance in advanced prostate cancer","volume":"42","author":"Seed","year":"2024","journal-title":"Cancer Cell"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Srivastava, T.P., Ajmeriya, S., Goel, I., Talukdar, J., Srivastava, A., Parshad, R., Deo, S.V.S., Mathur, S.R., Gogia, A., and Rai, A. (2024). Prognostic role of Androgen Receptor splice variant 7 (AR-V7) in the pathogenesis of breast cancer. BMC Cancer, 24.","DOI":"10.1186\/s12885-024-13165-x"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1053\/j.semnuclmed.2021.12.008","article-title":"The Impact of PSMA PET\/CT Imaging in Prostate Cancer Radiation Treatment","volume":"52","author":"Mena","year":"2022","journal-title":"Semin. Nucl. Med."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Zhu, S., Chen, J., and Zeng, H. (2023). Our Current Understanding of the Heterogeneity in Prostate Cancer and Renal Cell Carcinoma. J. Clin. Med., 12.","DOI":"10.3390\/jcm12041526"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1426","DOI":"10.1038\/s41467-021-21615-4","article-title":"Inter- and intra-tumor heterogeneity of metastatic prostate cancer determined by digital spatial gene expression profiling","volume":"12","author":"Brady","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"5070","DOI":"10.1038\/s41467-020-18843-5","article-title":"Prostate cancer evolution from multilineage primary to single lineage metastases with implications for liquid biopsy","volume":"11","author":"Woodcock","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Bruni, S., Mercogliano, M.F., Mauro, F.L., Cordo Russo, R.I., and Schillaci, R. (2023). Cancer immune exclusion: Breaking the barricade for a successful immunotherapy. Front. Oncol., 13.","DOI":"10.3389\/fonc.2023.1135456"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Tiwari, A., Oravecz, T., Dillon, L.A., Italiano, A., Audoly, L., Fridman, W.H., and Clifton, G.T. (2023). Towards a consensus definition of immune exclusion in cancer. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1084887"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1038\/s41419-023-06110-6","article-title":"Stromal cells in the tumor microenvironment: Accomplices of tumor progression?","volume":"14","author":"Zhao","year":"2023","journal-title":"Cell Death Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e006773","DOI":"10.1136\/jitc-2023-006773","article-title":"Developing a definition of immune exclusion in cancer: Results of a modified Delphi workshop","volume":"11","author":"Clifton","year":"2023","journal-title":"J. Immunother. Cancer"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1038\/s41392-020-00449-4","article-title":"Advantages of targeting the tumor immune microenvironment over blocking immune checkpoint in cancer immunotherapy","volume":"6","author":"Tang","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e125","DOI":"10.1017\/cts.2023.537","article-title":"Recent innovations in adaptive trial designs: A review of design opportunities in translational research","volume":"7","author":"Kaizer","year":"2023","journal-title":"J. Clin. Transl. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/s41392-024-01760-0","article-title":"New clinical trial design in precision medicine: Discovery, development and direction","volume":"9","author":"Duan","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.1016\/j.annonc.2020.06.004","article-title":"The forefront of ovarian cancer therapy: Update on PARP inhibitors","volume":"31","author":"Mirza","year":"2020","journal-title":"Ann. Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1007\/s11912-022-01278-0","article-title":"Integration of Liquid Biopsies in Clinical Management of Metastatic Prostate Cancer","volume":"24","author":"Tulpule","year":"2022","journal-title":"Curr. Oncol. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1394","DOI":"10.1038\/s41416-022-01881-9","article-title":"Blood-based liquid biopsies for prostate cancer: Clinical opportunities and challenges","volume":"127","author":"Trujillo","year":"2022","journal-title":"Br. J. Cancer"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1002\/cncr.35173","article-title":"Charles Brenton Huggins: A historical review of the Nobel laureate\u2019s pioneering discoveries","volume":"130","author":"Benadada","year":"2024","journal-title":"Cancer"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1038\/s41392-022-01042-7","article-title":"Targeting signaling pathways in prostate cancer: Mechanisms and clinical trials","volume":"7","author":"He","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Jacob, A., Raj, R., Allison, D.B., and Myint, Z.W. (2021). Androgen Receptor Signaling in Prostate Cancer and Therapeutic Strategies. Cancers, 13.","DOI":"10.20944\/preprints202110.0016.v1"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2279235","DOI":"10.1080\/07853890.2023.2279235","article-title":"Molecular classifications of prostate cancer: Basis for individualized risk stratification and precision therapy","volume":"55","author":"Ge","year":"2023","journal-title":"Ann. Med."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Li, C., Cheng, D., and Li, P. (2025). Androgen receptor dynamics in prostate cancer: From disease progression to treatment resistance. Front. Oncol., 15.","DOI":"10.3389\/fonc.2025.1542811"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"288","DOI":"10.5534\/wjmh.180040","article-title":"Role of Androgen Receptor in Prostate Cancer: A Review","volume":"37","author":"Fujita","year":"2019","journal-title":"World J. Mens. Health"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e168649","DOI":"10.1172\/JCI168649","article-title":"Androgen receptor splice variants drive castration-resistant prostate cancer metastasis by activating distinct transcriptional programs","volume":"134","author":"Han","year":"2024","journal-title":"J. Clin. Investig."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1158\/1538-7445.AM2019-1292","article-title":"Abstract 1292: A new generation of N-terminal domain androgen receptor inhibitors, with improved pharmaceutical properties, in castration-resistant prostate cancer models","volume":"79","author":"Moigne","year":"2019","journal-title":"Cancer Res."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Hung, C.L., Liu, H.H., Fu, C.W., Yeh, H.H., Hu, T.L., Kuo, Z.K., Lin, Y.C., Jhang, M.R., Hwang, C.S., and Hsu, H.C. (2023). Targeting androgen receptor and the variants by an orally bioavailable Proteolysis Targeting Chimeras compound in castration resistant prostate cancer. EBioMedicine, 90.","DOI":"10.1016\/j.ebiom.2023.104500"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Gokbayrak, B., Altintas, U.B., Lingadahalli, S., Morova, T., Huang, C.-C.F., Ersoy Fazlioglu, B., Pak Lok Yu, I., Kalkan, B.M., Cejas, P., and Kung, S.H.Y. (2025). Identification of selective SWI\/SNF dependencies in enzalutamide-resistant prostate cancer. Commun. Biol., 8.","DOI":"10.1038\/s42003-024-07413-w"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Wu, F., Zhang, H., and Hao, M. (2025). Interactions between key genes and pathways in prostate cancer progression and therapy resistance. Front. Oncol., 15.","DOI":"10.3389\/fonc.2025.1467540"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Zhou, L., Zhang, C., Zhang, Y., and Shi, C. (2021). Application of Organoid Models in Prostate Cancer Research. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.736431"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e2300057","DOI":"10.1200\/CCI.23.00057","article-title":"Multi-Omic Integration of Blood-Based Tumor-Associated Genomic and Lipidomic Profiles Using Machine Learning Models in Metastatic Prostate Cancer","volume":"7","author":"Fang","year":"2023","journal-title":"JCO Clin. Cancer Inform."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1038\/s41571-018-0055-6","article-title":"Synthetic lethal therapies for cancer: What\u2019s next after PARP inhibitors?","volume":"15","author":"Ashworth","year":"2018","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Catalano, M., Generali, D., Gatti, M., Riboli, B., Paganini, L., Nesi, G., and Roviello, G. (2023). DNA repair deficiency as circulating biomarker in prostate cancer. Front. Oncol., 13.","DOI":"10.3389\/fonc.2023.1115241"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Gong, X., Liu, C., Tang, H., Wu, S., and Yang, Q. (2024). Application and research progress of synthetic lethality in the development of anticancer therapeutic drugs. Front. Oncol., 14.","DOI":"10.3389\/fonc.2024.1460412"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Lukashchuk, N., Barnicle, A., Adelman, C.A., Armenia, J., Kang, J., Barrett, J.C., and Harrington, E.A. (2023). Impact of DNA damage repair alterations on prostate cancer progression and metastasis. Front. Oncol., 13.","DOI":"10.3389\/fonc.2023.1162644"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Harrision, D., Gravells, P., Thompson, R., and Bryant, H.E. (2020). Poly(ADP-Ribose) Glycohydrolase (PARG) vs. Poly(ADP-Ribose) Polymerase (PARP)\u2014Function in Genome Maintenance and Relevance of Inhibitors for Anti-cancer Therapy. Front. Mol. Biosci., 7.","DOI":"10.3389\/fmolb.2020.00191"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1038\/s41416-020-01114-x","article-title":"Genetic aberrations in DNA repair pathways: A cornerstone of precision oncology in prostate cancer","volume":"124","author":"Lozano","year":"2021","journal-title":"Br. J. Cancer"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1038\/s41416-023-02326-7","article-title":"PARP inhibitors: Enhancing efficacy through rational combinations","volume":"129","author":"Bhamidipati","year":"2023","journal-title":"Br. J. Cancer"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e390384","DOI":"10.1200\/EDBK_390384","article-title":"Genetic and Genomic Testing for Prostate Cancer: Beyond DNA Repair","volume":"43","author":"Herberts","year":"2023","journal-title":"Am. Soc. Clin. Oncol. Educ. Book"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/s41391-019-0153-2","article-title":"Role of the DNA damage response in prostate cancer formation, progression and treatment","volume":"23","author":"Zhang","year":"2020","journal-title":"Prostate Cancer Prostatic Dis."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Qian, J., Liao, G., Chen, M., Peng, R.-W., Yan, X., Du, J., Huang, R., Pan, M., Lin, Y., and Gong, X. (2024). Advancing cancer therapy: New frontiers in targeting DNA damage response. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1474337"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1038\/s41698-024-00526-9","article-title":"Convergent evolution of BRCA2 reversion mutations under therapeutic pressure by PARP inhibition and platinum chemotherapy","volume":"8","author":"Walmsley","year":"2024","journal-title":"npj Precis. Oncol."},{"key":"ref_49","first-page":"94","article-title":"TMPRSS2\u2013ERG Fusion Gene Expression in Prostate Tumor Cells and Its Clinical and Biological Significance in Prostate Cancer Progression","volume":"4","author":"Powell","year":"2012","journal-title":"J. Cancer Sci. Ther."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Lorenzin, F., and Demichelis, F. (2022). Past, Current, and Future Strategies to Target ERG Fusion-Positive Prostate Cancer. Cancers, 14.","DOI":"10.3390\/cancers14051118"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Scaravilli, M., Koivukoski, S., and Latonen, L. (2021). Androgen-Driven Fusion Genes and Chimeric Transcripts in Prostate Cancer. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.623809"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"5251","DOI":"10.1038\/s41467-019-13084-7","article-title":"The genomic landscape of metastatic castration-resistant prostate cancers reveals multiple distinct genotypes with potential clinical impact","volume":"10","author":"Smits","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"He, J., Zhang, C., Ozkan, A., Feng, T., Duan, P., Wang, S., Yang, X., Xie, J., and Liu, X. (2023). Patient-derived tumor models and their distinctive applications in personalized drug therapy. Mechanobiol. Med., 1.","DOI":"10.1016\/j.mbm.2023.100014"},{"key":"ref_54","first-page":"410","article-title":"Association between TMPRSS2: ERG fusion gene and the prostate cancer: Systematic review and meta-analysis","volume":"71","author":"Chaves","year":"2018","journal-title":"Cent. Eur. J. Urol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1038\/onc.2015.109","article-title":"The oncogene ERG: A key factor in prostate cancer","volume":"35","author":"Adamo","year":"2016","journal-title":"Oncogene"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1690","DOI":"10.1038\/sj.bjc.6604054","article-title":"Expression of the TMPRSS2: ERG fusion gene predicts cancer recurrence after surgery for localised prostate cancer","volume":"97","author":"Nam","year":"2007","journal-title":"Br. J. Cancer"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Turnham, D.J., Bullock, N., Dass, M.S., Staffurth, J.N., and Pearson, H.B. (2020). The PTEN Conundrum: How to Target PTEN-Deficient Prostate Cancer. Cells, 9.","DOI":"10.3390\/cells9112342"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1007\/s12079-022-00702-1","article-title":"Targeting PI3K\/Akt signaling in prostate cancer therapy","volume":"17","author":"Hashemi","year":"2023","journal-title":"J. Cell Commun. Signal"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Raith, F., O\u2019Donovan, D.H., Lemos, C., Politz, O., and Haendler, B. (2023). Addressing the Reciprocal Crosstalk between the AR and the PI3K\/AKT\/mTOR Signaling Pathways for Prostate Cancer Treatment. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24032289"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"e175949","DOI":"10.1172\/JCI175949","article-title":"Interruption of KLF5 acetylation promotes PTEN-deficient prostate cancer progression by reprogramming cancer-associated fibroblasts","volume":"134","author":"Zhang","year":"2024","journal-title":"J. Clin. Investig."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"e2300562","DOI":"10.1200\/PO.23.00562","article-title":"Real-World Overall Survival and Treatment Patterns by PTEN Status in Metastatic Castration-Resistant Prostate Cancer","volume":"8","author":"Gupta","year":"2024","journal-title":"JCO Precis. Oncol."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Shorning, B.Y., Dass, M.S., Smalley, M.J., and Pearson, H.B. (2020). The PI3K-AKT-mTOR Pathway and Prostate Cancer: At the Crossroads of AR, MAPK, and WNT Signaling. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21124507"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1038\/s41388-023-02875-4","article-title":"PTEN-regulated PI3K-p110 and AKT isoform plasticity controls metastatic prostate cancer progression","volume":"43","author":"Miller","year":"2024","journal-title":"Oncogene"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1334","DOI":"10.1038\/s43018-024-00787-0","article-title":"Tumor evolution metrics predict recurrence beyond 10 years in locally advanced prostate cancer","volume":"5","author":"Cresswell","year":"2024","journal-title":"Nat. Cancer"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"4823","DOI":"10.1038\/s41467-023-40315-9","article-title":"Copy number architectures define treatment-mediated selection of lethal prostate cancer clones","volume":"14","author":"Hasan","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Imamura, J., Ganguly, S., Muskara, A., Liao, R.S., Nguyen, J.K., Weight, C., Wee, C.E., Gupta, S., and Mian, O.Y. (2023). Lineage plasticity and treatment resistance in prostate cancer: The intersection of genetics, epigenetics, and evolution. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1191311"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1186\/s13073-021-00895-x","article-title":"Modeling clonal structure over narrow time frames via circulating tumor DNA in metastatic breast cancer","volume":"13","author":"Weber","year":"2021","journal-title":"Genome Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"6605","DOI":"10.1038\/ncomms7605","article-title":"Tracking the origins and drivers of subclonal metastatic expansion in prostate cancer","volume":"6","author":"Hong","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1038\/s41698-022-00272-w","article-title":"Tumor microenvironment heterogeneity an important mediator of prostate cancer progression and therapeutic resistance","volume":"6","author":"Ge","year":"2022","journal-title":"npj Precis. Oncol."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Peter, M.R., Bilenky, M., Davies, A., Isserlin, R., Bader, G.D., Fleshner, N.E., Hirst, M., Zoubeidi, A., and Bapat, B. (2021). Distinct DNA methylation patterns associated with treatment resistance in metastatic castration resistant prostate cancer. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-85812-3"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"e167440","DOI":"10.1172\/jci.insight.167440","article-title":"LSD1 promotes prostate cancer reprogramming by repressing TP53 signaling independently of its demethylase function","volume":"8","author":"Kumaraswamy","year":"2023","journal-title":"JCI Insight"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Koushyar, S., Meniel, V.S., Phesse, T.J., and Pearson, H.B. (2022). Exploring the Wnt Pathway as a Therapeutic Target for Prostate Cancer. Biomolecules, 12.","DOI":"10.3390\/biom12020309"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"367","DOI":"10.4143\/crt.2023.446","article-title":"Utilizing Plasma Circulating Tumor DNA Sequencing for Precision Medicine in the Management of Solid Cancers","volume":"55","author":"Cha","year":"2023","journal-title":"Cancer Res. Treat."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.omto.2023.04.007","article-title":"New insights and options into the mechanisms and effects of combined targeted therapy and immunotherapy in prostate cancer","volume":"29","author":"Lin","year":"2023","journal-title":"Mol. Ther. Oncolytics"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Wang, H.-C., Xia, R., Chang, W.-H., Hsu, S.-W., Wu, C.-T., Chen, C.-H., and Shih, T.-C. (2024). Improving cancer immunotherapy in prostate cancer by modulating T cell function through targeting the galectin-1. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1372956"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Ren, X., Chen, X., Zhang, X., Jiang, S., Zhang, T., Li, G., Lu, Z., Zhang, D., Wang, S., and Qin, C. (2021). Immune Microenvironment and Response in Prostate Cancer Using Large Population Cohorts. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.686809"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1038\/s41467-023-36325-2","article-title":"Dissecting the immune suppressive human prostate tumor microenvironment via integrated single-cell and spatial transcriptomic analyses","volume":"14","author":"Hirz","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000541881","article-title":"The Immune Microenvironment in Prostate Cancer: A Comprehensive Review","volume":"9","author":"Novysedlak","year":"2024","journal-title":"Oncology"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"van Genderen, M.N.G., Kneppers, J., Zaalberg, A., Bekers, E.M., Bergman, A.M., Zwart, W., and Eduati, F. (2024). Agent-based modeling of the prostate tumor microenvironment uncovers spatial tumor growth constraints and immunomodulatory properties. npj Syst. Biol. Appl., 10.","DOI":"10.1038\/s41540-024-00344-6"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1038\/s41391-021-00340-5","article-title":"How to turn up the heat on the cold immune microenvironment of metastatic prostate cancer","volume":"24","author":"Stultz","year":"2021","journal-title":"Prostate Cancer Prostatic Dis."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.trecan.2024.01.004","article-title":"Epigenetic underpinnings of tumor-immune dynamics in prostate cancer immune suppression","volume":"10","author":"Angappulige","year":"2024","journal-title":"Trends Cancer"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"694","DOI":"10.37349\/etat.2022.00108","article-title":"The tumor innate immune microenvironment in prostate cancer: An overview of soluble factors and cellular effectors","volume":"3","author":"Palano","year":"2022","journal-title":"Explor. Target. Anti-Tumor Ther."},{"key":"ref_83","first-page":"199","article-title":"Singling out the immune-suppressive TME in prostate cancer","volume":"20","author":"Stone","year":"2023","journal-title":"Nat. Rev. Urol."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Liang, H., Liu, Y., Guo, J., Dou, M., Zhang, X., Hu, L., and Chen, J. (2023). Progression in immunotherapy for advanced prostate cancer. Front. Oncol., 13.","DOI":"10.3389\/fonc.2023.1126752"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Kobayashi, T., Nagata, M., Hachiya, T., Wakita, H., Ikehata, Y., Takahashi, K., China, T., Shimizu, F., Lu, J., and Jin, Y. (2024). Increased circulating polymorphonuclear myeloid-derived suppressor cells are associated with prognosis of metastatic castration-resistant prostate cancer. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1372771"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1038\/s41586-024-08290-3","article-title":"Evolution of myeloid-mediated immunotherapy resistance in prostate cancer","volume":"637","author":"Lyu","year":"2025","journal-title":"Nature"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1743","DOI":"10.1172\/JCI132031","article-title":"Genomics of lethal prostate cancer at diagnosis and castration resistance","volume":"130","author":"Mateo","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1200\/OP.21.00206","article-title":"Recent Advances in the Management of Metastatic Prostate Cancer","volume":"18","author":"Sayegh","year":"2022","journal-title":"JCO Oncol. Pract."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1016\/j.cell.2015.05.001","article-title":"Integrative clinical genomics of advanced prostate cancer","volume":"161","author":"Robinson","year":"2015","journal-title":"Cell"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1856","DOI":"10.1038\/s12276-024-01288-x","article-title":"Clinical application of whole-genome sequencing of solid tumors for precision oncology","volume":"56","author":"Kim","year":"2024","journal-title":"Exp. Mol. Med."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Satam, H., Joshi, K., Mangrolia, U., Waghoo, S., Zaidi, G., Rawool, S., Thakare, R.P., Banday, S., Mishra, A.K., and Das, G. (2023). Next-Generation Sequencing Technology: Current Trends and Advancements. Biology, 12.","DOI":"10.3390\/biology12070997"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"S86","DOI":"10.1002\/pros.24354","article-title":"Future directions for precision oncology in prostate cancer","volume":"82","author":"Mizuno","year":"2022","journal-title":"Prostate"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1016\/j.cell.2016.12.015","article-title":"Implementing Genome-Driven Oncology","volume":"168","author":"Hyman","year":"2017","journal-title":"Cell"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"e2300654","DOI":"10.1200\/PO.23.00654","article-title":"Toward Informed Selection and Interpretation of Clinical Genomic Tests in Prostate Cancer","volume":"8","author":"Vandekerkhove","year":"2024","journal-title":"JCO Precis. Oncol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"3432","DOI":"10.3390\/curroncol30030260","article-title":"Future of Artificial Intelligence Applications in Cancer Care: A Global Cross-Sectional Survey of Researchers","volume":"30","author":"Cabral","year":"2023","journal-title":"Curr. Oncol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"3509","DOI":"10.1158\/1078-0432.CCR-22-0851","article-title":"Assessment of Androgen Receptor Splice Variant-7 as a Biomarker of Clinical Response in Castration-Sensitive Prostate Cancer","volume":"28","author":"Sowalsky","year":"2022","journal-title":"Clin. Cancer Res."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1038\/s12276-023-00934-0","article-title":"Superenhancers as master gene regulators and novel therapeutic targets in brain tumors","volume":"55","author":"Zhuang","year":"2023","journal-title":"Exp. Mol. Med."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1038\/s41467-021-27322-4","article-title":"Single-cell analysis of human primary prostate cancer reveals the heterogeneity of tumor-associated epithelial cell states","volume":"13","author":"Song","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Ruprecht, N.A., Kennedy, J.D., Bansal, B., Singhal, S., Sens, D., Maggio, A., Doe, V., Hawkins, D., Campbel, R., and O\u2019Connell, K. (2024). Transcriptomics and epigenetic data integration learning module on Google Cloud. Brief. Bioinform., 25.","DOI":"10.1093\/bib\/bbae352"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1007\/s00439-019-01970-5","article-title":"Translating cancer genomics into precision medicine with artificial intelligence: Applications, challenges and future perspectives","volume":"138","author":"Xu","year":"2019","journal-title":"Hum. Genet."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"9949","DOI":"10.1038\/s41467-024-54364-1","article-title":"Single cell and spatial transcriptomics highlight the interaction of club-like cells with immunosuppressive myeloid cells in prostate cancer","volume":"15","author":"Kiviaho","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1038\/s41416-024-02935-w","article-title":"Semi-mechanistic efficacy model for PARP\u2009+\u2009ATR inhibitors\u2014Application to rucaparib and talazoparib in combination with gartisertib in breast cancer PDXs","volume":"132","author":"Villette","year":"2025","journal-title":"Br. J. Cancer"},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Ragupathi, A., Singh, M., Perez, A.M., and Zhang, D. (2023). Targeting the BRCA1\/2 deficient cancer with PARP inhibitors: Clinical outcomes and mechanistic insights. Front. Cell Dev. Biol., 11.","DOI":"10.3389\/fcell.2023.1133472"},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Miller, K.J., Henry, I., Maylin, Z., Smith, C., Arunachalam, E., Pandha, H., and Asim, M. (2023). A compendium of Androgen Receptor Variant 7 target genes and their role in Castration Resistant Prostate Cancer. Front. Oncol., 13.","DOI":"10.3389\/fonc.2023.1129140"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"e433138","DOI":"10.1200\/EDBK_433138","article-title":"Advancing Prostate Cancer Care: Treatment Approaches to Precision Medicine, Biomarker Innovations, and Equitable Access","volume":"44","author":"Fenton","year":"2024","journal-title":"Am. Soc. Clin. Oncol. Educ. Book"},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Vidovi\u0107, V., Davidov, I., Ru\u017ei\u0107, Z., Erdeljan, M., Galfi Vukomanovi\u0107, A., and Blagojevi\u0107, B. (2025). Androgen Receptors in Human Breast Cancer and Female Canine Mammary Tumors. Molecules, 30.","DOI":"10.3390\/molecules30071411"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1186\/s12967-022-03765-1","article-title":"Integration of CRISPR\/Cas9 with artificial intelligence for improved cancer therapeutics","volume":"20","author":"Bhat","year":"2022","journal-title":"J. Transl. Med."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"831","DOI":"10.3892\/ol.2021.13092","article-title":"Ratio of the expression levels of androgen receptor splice variant 7 to androgen receptor in castration refractory prostate cancer","volume":"22","author":"Sekine","year":"2021","journal-title":"Oncol. Lett."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"S1441","DOI":"10.21037\/tcr.2017.10.49","article-title":"The evolving role of molecular profiling in prostate cancer: Basal and luminal subtyping transcends tissue of origin","volume":"6","author":"Mian","year":"2017","journal-title":"Transl. Cancer Res."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1016\/S0140-6736(20)30314-7","article-title":"Prostate-specific membrane antigen PET-CT in patients with high-risk prostate cancer before curative-intent surgery or radiotherapy (proPSMA): A prospective, randomised, multicentre study","volume":"395","author":"Hofman","year":"2020","journal-title":"Lancet"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1001\/jamaoncol.2019.0096","article-title":"Assessment of 68Ga-PSMA-11 PET Accuracy in Localizing Recurrent Prostate Cancer: A Prospective Single-Arm Clinical Trial","volume":"5","author":"Fendler","year":"2019","journal-title":"JAMA Oncol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"266","DOI":"10.2214\/AJR.18.20699","article-title":"Single-Center Prospective Evaluation of (68)Ga-PSMA-11 PET in Biochemical Recurrence of Prostate Cancer","volume":"213","author":"Flavell","year":"2019","journal-title":"AJR Am. J. Roentgenol."},{"key":"ref_113","first-page":"S38","article-title":"Disparities in prostate cancer","volume":"115","author":"Burnett","year":"2023","journal-title":"J. Natl. Med. Assoc."},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Wang, Q., Ketteler, S., Bagheri, S., Ebrahimifard, A., Luster, M., Librizzi, D., and Yousefi, B.H. (2024). Diagnostic efficacy of [99mTc]Tc-PSMA SPECT\/CT for prostate cancer: A meta-analysis. BMC Cancer, 24.","DOI":"10.1186\/s12885-024-12734-4"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"801","DOI":"10.2967\/jnumed.119.227967","article-title":"(68)Ga-FAPI PET\/CT: Tracer Uptake in 28 Different Kinds of Cancer","volume":"60","author":"Kratochwil","year":"2019","journal-title":"J. Nucl. Med."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"e722","DOI":"10.1002\/mco2.722","article-title":"Radiogenomics: Bridging the gap between imaging and genomics for precision oncology","volume":"5","author":"He","year":"2024","journal-title":"MedComm"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.1007\/s00259-016-3419-0","article-title":"Radiation dosimetry of (68)Ga-PSMA-11 (HBED-CC) and preliminary evaluation of optimal imaging timing","volume":"43","author":"Hetzheim","year":"2016","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1080\/23808993.2016.1164013","article-title":"Radiomics: A new application from established techniques","volume":"1","author":"Parekh","year":"2016","journal-title":"Expert. Rev. Precis. Med. Drug Dev."},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"von Stauffenberg, F., Poyet, C., Beintner-Skawran, S., Maurer, A., and Schmid, F.A. (2024). Current Clinical Applications of PSMA-PET for Prostate Cancer Diagnosis, Staging, and Treatment. Cancers, 16.","DOI":"10.3390\/cancers16244263"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1636","DOI":"10.1038\/s41591-024-02979-8","article-title":"PSCA-CAR T cell therapy in metastatic castration-resistant prostate cancer: A phase 1 trial","volume":"30","author":"Dorff","year":"2024","journal-title":"Nat. Med."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s12943-023-01925-5","article-title":"Comprehensive review of CRISPR-based gene editing: Mechanisms, challenges, and applications in cancer therapy","volume":"23","author":"Chehelgerdi","year":"2024","journal-title":"Mol. Cancer"},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Ozaki, Y., Broughton, P., Abdollahi, H., Valafar, H., and Blenda, A.V. (2024). Integrating Omics Data and AI for Cancer Diagnosis and Prognosis. Cancers, 16.","DOI":"10.20944\/preprints202406.0657.v1"},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Allen, T.A. (2024). The Role of Circulating Tumor Cells as a Liquid Biopsy for Cancer: Advances, Biology, Technical Challenges, and Clinical Relevance. Cancers, 16.","DOI":"10.3390\/cancers16071377"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1038\/s41392-024-01938-6","article-title":"Circulating tumor cells: From new biological insights to clinical practice","volume":"9","author":"Gu","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1111\/iju.15441","article-title":"Prostate cancer and liquid biopsies: Clinical applications and challenges","volume":"31","author":"Urabe","year":"2024","journal-title":"Int. J. Urol."},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Wang, X., Wang, L., Lin, H., Zhu, Y., Huang, D., Lai, M., Xi, X., Huang, J., Zhang, W., and Zhong, T. (2024). Research progress of CTC, ctDNA, and EVs in cancer liquid biopsy. Front. Oncol., 14.","DOI":"10.3389\/fonc.2024.1303335"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"2745","DOI":"10.1158\/1078-0432.CCR-23-1043","article-title":"Circulating Tumor DNA Biomarkers for Response Assessment in Prostate Cancer","volume":"29","author":"Sartor","year":"2023","journal-title":"Clin. Cancer Res."},{"key":"ref_128","doi-asserted-by":"crossref","unstructured":"Liu, C., Xia, C., and Xia, C. (2023). Biology and function of exosomes in tumor immunotherapy. Biomed. Pharmacother., 169.","DOI":"10.1016\/j.biopha.2023.115853"},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Zheng, Z., Li, J., Liu, Y., Shi, Z., Xuan, Z., Yang, K., Xu, C., Bai, Y., Fu, M., and Xiao, Q. (2022). The Crucial Role of AR-V7 in Enzalutamide-Resistance of Castration-Resistant Prostate Cancer. Cancers, 14.","DOI":"10.3390\/cancers14194877"},{"key":"ref_130","doi-asserted-by":"crossref","unstructured":"Crocetto, F., Russo, G., Di Zazzo, E., Pisapia, P., Mirto, B.F., Palmieri, A., Pepe, F., Bellevicine, C., Russo, A., and La Civita, E. (2022). Liquid Biopsy in Prostate Cancer Management-Current Challenges and Future Perspectives. Cancers, 14.","DOI":"10.3390\/cancers14133272"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"2695","DOI":"10.3390\/cimb44060184","article-title":"Current and Future Perspectives of Cell-Free DNA in Liquid Biopsy","volume":"44","author":"Liu","year":"2022","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1200\/EDBK_359650","article-title":"Global Challenges in Access to and Implementation of Precision Oncology: The Health Care Manager and Health Economist Perspective","volume":"42","author":"Shih","year":"2022","journal-title":"Am. Soc. Clin. Oncol. Educ. Book"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1016\/j.ccell.2022.09.012","article-title":"Artificial intelligence for multimodal data integration in oncology","volume":"40","author":"Lipkova","year":"2022","journal-title":"Cancer Cell"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/s12943-024-02215-4","article-title":"Emerging role of exosomes in cancer therapy: Progress and challenges","volume":"24","author":"Li","year":"2025","journal-title":"Mol. Cancer"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1038\/s41392-024-02021-w","article-title":"Liquid biopsy in cancer: Current status, challenges and future prospects","volume":"9","author":"Ma","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"e2454253","DOI":"10.1001\/jamanetworkopen.2024.54253","article-title":"Androgen Receptor Pathway Inhibitor Therapy for Advanced Prostate Cancer: Secondary Analysis of a Randomized Clinical Trial","volume":"8","author":"Bastos","year":"2025","journal-title":"JAMA Netw. Open"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"17588359231221337","DOI":"10.1177\/17588359231221337","article-title":"Development of PARP inhibitors in advanced prostate cancer","volume":"16","author":"Bourlon","year":"2024","journal-title":"Ther. Adv. Med. Oncol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1200\/JCO.20.02759","article-title":"TRANSFORMER: A Randomized Phase II Study Comparing Bipolar Androgen Therapy Versus Enzalutamide in Asymptomatic Men With Castration-Resistant Metastatic Prostate Cancer","volume":"39","author":"Denmeade","year":"2021","journal-title":"J. Clin. Oncol."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1038\/s41467-023-44514-2","article-title":"Bipolar androgen therapy plus nivolumab for patients with metastatic castration-resistant prostate cancer: The COMBAT phase II trial","volume":"15","author":"Markowski","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"551","DOI":"10.21873\/anticanres.14807","article-title":"PARP Inhibitors in Prostate Cancer","volume":"41","author":"Grewal","year":"2021","journal-title":"Anticancer. Res."},{"key":"ref_141","doi-asserted-by":"crossref","unstructured":"Chen, Q.H., Munoz, E., and Ashong, D. (2024). Insight into Recent Advances in Degrading Androgen Receptor for Castration-Resistant Prostate Cancer. Cancers, 16.","DOI":"10.3390\/cancers16030663"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"107234","DOI":"10.1016\/j.phrs.2024.107234","article-title":"PROTACs targeting androgen receptor signaling: Potential therapeutic agents for castration-resistant prostate cancer","volume":"205","author":"Zhang","year":"2024","journal-title":"Pharmacol. Res."},{"key":"ref_143","doi-asserted-by":"crossref","unstructured":"Merlin, J.P.J., and Abrahamse, H. (2024). Optimizing CRISPR\/Cas9 precision: Mitigating off-target effects for safe integration with photodynamic and stem cell therapies in cancer treatment. Biomed. Pharmacother., 180.","DOI":"10.1016\/j.biopha.2024.117516"},{"key":"ref_144","doi-asserted-by":"crossref","unstructured":"Serrano, D.R., Luciano, F.C., Anaya, B.J., Ongoren, B., Kara, A., Molina, G., Ramirez, B.I., S\u00e1nchez-Guirales, S.A., Simon, J.A., and Tomietto, G. (2024). Artificial Intelligence (AI) Applications in Drug Discovery and Drug Delivery: Revolutionizing Personalized Medicine. Pharmaceutics, 16.","DOI":"10.3390\/pharmaceutics16101328"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"e390166","DOI":"10.1200\/EDBK_390166","article-title":"Metastatic Hormone-Sensitive Prostate Cancer: Toward an Era of Adaptive and Personalized Treatment","volume":"43","author":"Hamid","year":"2023","journal-title":"Am. Soc. Clin. Oncol. Educ. Book"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"405","DOI":"10.32604\/or.2023.028310","article-title":"Targeting DNA repair for cancer treatment: Lessons from PARP inhibitor trials","volume":"31","author":"Nambiar","year":"2023","journal-title":"Oncol. Res."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"e54086","DOI":"10.2196\/54086","article-title":"Carboplatin in Patients With Metastatic Castration-Resistant Prostate Cancer Harboring Somatic or Germline Homologous Recombination Repair Gene Mutations: Phase II Single-Arm Trial","volume":"13","author":"Jain","year":"2024","journal-title":"JMIR Res. Protoc."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1200\/JCO.2025.43.5_suppl.403","article-title":"Genomic alterations and their pathologic responses in high-risk localized prostate cancer (HRLPC) in subprotocol 1 of the Genomic Umbrella Neoadjuvant study (GUNS)","volume":"43","author":"Gleave","year":"2025","journal-title":"J. Clin. Oncol."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"TPS279","DOI":"10.1200\/JCO.2025.43.5_suppl.TPS279","article-title":"Phase III, double-blind, placebo-controlled, 2-cohort, randomized study of saruparib (AZD5305) in combination with androgen receptor pathway inhibitors in patients with metastatic hormone-sensitive prostate cancer with and without homologous recombination repair mutation (EvoPAR-Prostate01)","volume":"43","author":"Azad","year":"2025","journal-title":"J. Clin. Oncol."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"TPS178","DOI":"10.1200\/JCO.2021.39.6_suppl.TPS178","article-title":"A phase III trial of capivasertib and abiraterone versus placebo and abiraterone in patients with de novo metastatic hormone-sensitive prostate cancer characterized by PTEN deficiency (CAPItello-281)","volume":"39","author":"Fizazi","year":"2021","journal-title":"J. Clin. Oncol."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/S0140-6736(21)00580-8","article-title":"Ipatasertib plus abiraterone and prednisolone in metastatic castration-resistant prostate cancer (IPATential150): A multicentre, randomised, double-blind, phase 3 trial","volume":"398","author":"Sweeney","year":"2021","journal-title":"Lancet"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1158\/0008-5472.CAN-22-1890","article-title":"Stromal Reprogramming through Dual PDGFR\u03b1\/\u03b2 Blockade Boosts the Efficacy of Anti\u2013PD-1 Immunotherapy in Fibrotic Tumors","volume":"83","author":"Akiyama","year":"2023","journal-title":"Cancer Res."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"R35","DOI":"10.1530\/ERC-19-0420","article-title":"The epigenetic and transcriptional landscape of neuroendocrine prostate cancer","volume":"27","author":"Davies","year":"2020","journal-title":"Endocr. -Relat. Cancer"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"3200","DOI":"10.1158\/1078-0432.CCR-24-0400","article-title":"Evaluating Immune Checkpoint Blockade in Metastatic Castration-Resistant Prostate Cancers with Deleterious CDK12 Alterations in the Phase 2 IMPACT Trial","volume":"30","author":"Nguyen","year":"2024","journal-title":"Clin. Cancer Res."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1158\/2326-6066.CIR-22-0306","article-title":"Randomized Phase II Study Evaluating the Addition of Pembrolizumab to Radium-223 in Metastatic Castration-resistant Prostate Cancer","volume":"12","author":"Choudhury","year":"2024","journal-title":"Cancer Immunol. Res."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"2041","DOI":"10.1038\/s41467-023-37874-2","article-title":"Targeting advanced prostate cancer with STEAP1 chimeric antigen receptor T cell and tumor-localized IL-12 immunotherapy","volume":"14","author":"Bhatia","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1038\/s41392-024-01853-w","article-title":"Antitumor efficacy and potential mechanism of FAP-targeted radioligand therapy combined with immune checkpoint blockade","volume":"9","author":"Zhao","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"1756287220951404","DOI":"10.1177\/1756287220951404","article-title":"Immunotherapy in prostate cancer: Current state and future perspectives","volume":"12","author":"Handa","year":"2020","journal-title":"Ther. Adv. Urol."},{"key":"ref_159","doi-asserted-by":"crossref","unstructured":"Nakamura, H., Arihara, Y., and Takada, K. (2023). Targeting STEAP1 as an anticancer strategy. Front. Oncol., 13.","DOI":"10.3389\/fonc.2023.1285661"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1158\/2159-8290.CD-23-0964","article-title":"Xaluritamig, a STEAP1 \u00d7 CD3 XmAb 2+1 Immune Therapy for Metastatic Castration-Resistant Prostate Cancer: Results from Dose Exploration in a First-in-Human Study","volume":"14","author":"Kelly","year":"2024","journal-title":"Cancer Discov."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"e17061","DOI":"10.1200\/JCO.2024.42.16_suppl.e17061","article-title":"Efficacy and toxicity of [177Lu]Lu-PSMA-617 for metastatic castration-resistant prostate cancer in a real-world setting: Results from the U.S. Expanded Access Program and comparisons with phase 3 VISION data","volume":"42","author":"Calais","year":"2024","journal-title":"J. Clin. Oncol."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"e24857","DOI":"10.1002\/pros.24857","article-title":"The Safety and Efficacy of Targeted Alpha Therapy, Ac-225 Prostate-Specific Membrane Antigen, in Patients With Metastatic Castration-Resistant Prostate Cancer: A Systematic Review and Meta-Analysis","volume":"85","author":"Besiroglu","year":"2025","journal-title":"Prostate"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.2967\/jnumed.124.267650","article-title":"Clinical Trial Protocol for VIOLET: A Single-Center, Phase I\/II Trial Evaluation of Radioligand Treatment in Patients with Metastatic Castration-Resistant Prostate Cancer with [161Tb]Tb-PSMA-I&T","volume":"65","author":"Buteau","year":"2024","journal-title":"J. Nucl. Med."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"TPS289","DOI":"10.1200\/JCO.2025.43.5_suppl.TPS289","article-title":"CONVERGE-01: Dosimetry, randomized dose optimization, dose escalation, and efficacy of ac-225 rosopatamab tetraxetan in participants with PSMA-positive castration-resistant prostate cancer","volume":"43","author":"Morris","year":"2025","journal-title":"J. Clin. Oncol."},{"key":"ref_165","unstructured":"(2025, February 28). ClinicalTrials.gov. Phase I\/II Study of [225Ac]Ac-PSMA-R2 in PSMA-Positive Prostate Cancer, with\/Without Prior 177Lu-PSMA RLT. Identifier: NCT05983198. Updated [31 January 2025], Available online: https:\/\/clinicaltrials.gov\/study\/NCT05983198."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"TPS271","DOI":"10.1200\/JCO.2023.41.6_suppl.TPS271","article-title":"Evolution: Phase II study of radionuclide 177Lu-PSMA-617 therapy versus 177Lu-PSMA-617 in combination with ipilimumab and nivolumab for men with metastatic castration-resistant prostate cancer (mCRPC.; ANZUP 2001)","volume":"41","author":"Sandhu","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"TPS280","DOI":"10.1200\/JCO.2023.41.6_suppl.TPS280","article-title":"AlphaBet: A phase I\/II trial evaluating the combination of radium-223 and [177Lu]Lu-PSMA-I&T in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC)","volume":"41","author":"Kostos","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_168","doi-asserted-by":"crossref","unstructured":"Ruigrok, E.A.M., Verkaik, N.S., de Blois, E., de Ridder, C., Stuurman, D., Roobol, S.J., Van Gent, D.C., de Jong, M., Van Weerden, W.M., and Nonnekens, J. (2022). Preclinical Assessment of the Combination of PSMA-Targeting Radionuclide Therapy with PARP Inhibitors for Prostate Cancer Treatment. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23148037"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"102699","DOI":"10.1016\/j.ctrv.2024.102699","article-title":"177Lu-PSMA therapy in metastatic prostate cancer: An updated review of prognostic and predictive biomarkers","volume":"125","author":"Giunta","year":"2024","journal-title":"Cancer Treat. Rev."},{"key":"ref_170","doi-asserted-by":"crossref","unstructured":"Perrone, E., Giordano, A., Calcagni, M.L., Leccisotti, L., Moretti, R., Eismant, A., Ghai, K., Parkar, T., Mishra, A., and Heidenreich, A. (2025). Long-Term Safety and Survival Outcomes of [(225)Ac]Ac-PSMA (Prostate-Specific Membrane Antigen) and [(225)Ac]Ac-\/[(177)Lu]Lu-PSMA (TANDEM) Radioligand Therapy (PRLT) in Metastatic Castration-Resistant Prostate Cancer. Cancers, 17.","DOI":"10.3390\/cancers17030405"},{"key":"ref_171","doi-asserted-by":"crossref","unstructured":"Wang, H., Li, G., Zhao, J., Eiber, M., and Tian, R. (2024). Current status of PSMA-targeted imaging and therapy. Front. Oncol., 13.","DOI":"10.3389\/fonc.2023.1230251"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"100164","DOI":"10.1016\/j.ctarc.2020.100164","article-title":"Emerging treatments for metastatic castration-resistant prostate cancer: Immunotherapy, PARP inhibitors, and PSMA-targeted approaches","volume":"23","author":"Marshall","year":"2020","journal-title":"Cancer Treat. Res. Commun."},{"key":"ref_173","doi-asserted-by":"crossref","unstructured":"Karimzadeh, A., Lehnert, W., Koehler, D., Shenas, F., Kisters, A., Apostolova, I., Klutmann, S., Adam, G., and Sauer, M. (2025). Overview of selected completed prospective studies on PSMA-targeted radioligand therapy with [177Lu]Lu-PSMA-617 in metastatic castration-resistant prostate cancer. Rofo.","DOI":"10.1055\/a-2514-4523"},{"key":"ref_174","doi-asserted-by":"crossref","unstructured":"Hachem, S., Yehya, A., El Masri, J., Mavingire, N., Johnson, J.R., Dwead, A.M., Kattour, N., Bouchi, Y., Kobeissy, F., and Rais-Bahrami, S. (2024). Contemporary Update on Clinical and Experimental Prostate Cancer Biomarkers: A Multi-Omics-Focused Approach to Detection and Risk Stratification. Biology, 13.","DOI":"10.3390\/biology13100762"},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"2091","DOI":"10.1056\/NEJMoa1911440","article-title":"Olaparib for Metastatic Castration-Resistant Prostate Cancer","volume":"382","author":"Bono","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1056\/NEJMoa2107322","article-title":"Lutetium-177\u2013PSMA-617 for Metastatic Castration-Resistant Prostate Cancer","volume":"385","author":"Sartor","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/j.ccell.2020.08.007","article-title":"Nivolumab Plus Ipilimumab for Metastatic Castration-Resistant Prostate Cancer: Preliminary Analysis of Patients in the CheckMate 650 Trial","volume":"38","author":"Sharma","year":"2020","journal-title":"Cancer Cell"},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1200\/JCO.19.01638","article-title":"Pembrolizumab for Treatment-Refractory Metastatic Castration-Resistant Prostate Cancer: Multicohort, Open-Label Phase II KEYNOTE-199 Study","volume":"38","author":"Antonarakis","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.eururo.2020.08.011","article-title":"Apalutamide and Overall Survival in Prostate Cancer","volume":"79","author":"Smith","year":"2021","journal-title":"Eur. 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