{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T21:33:58Z","timestamp":1792704838003,"version":"4.5.0"},"reference-count":80,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T00:00:00Z","timestamp":1761523200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Despite advances in diagnostic and therapeutic technology, prostate cancer remains a leading cause of morbidity and mortality among men. While androgen deprivation therapy and next-generation androgen receptor pathway inhibitors offer durable responses, the emergence of the lethal phenotype, metastatic castration-resistant prostate cancer (mCRPC) eventually develops for most. A growing body of evidence points to the tumor microenvironment (TME) as a key driver of immune evasion and therapeutic failure. This review focuses on the current knowledge of immune suppression in the prostate TME, including cancer-associated fibroblasts, myeloid-derived suppressor cells, tumor-associated macrophages, immune checkpoint pathways, and several associated key metabolic alterations. These cellular and molecular networks contribute to therapeutic resistance and disease progression and may be used as therapeutic targets. We will also examine emerging treatment strategies aimed at reprogramming the TME, as well as combination approaches incorporating immunotherapies with other signaling inhibitors. Future success in clinical therapeutic development for mCRPC will depend on rational combinations that address both tumor-intrinsic resistance and extrinsic immune suppression, with emphasis on biomarker-driven patient and treatment selection.<\/jats:p>","DOI":"10.3390\/cancers17213441","type":"journal-article","created":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T17:02:01Z","timestamp":1761670921000},"page":"3441","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Overcoming Immune Evasion in the Prostate Tumor Microenvironment: Novel Targeted Strategies to Improve Treatment Outcomes"],"prefix":"10.3390","volume":"17","author":[{"given":"Jing","family":"Huang","sequence":"first","affiliation":[{"name":"Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ademola","family":"Ojo","sequence":"additional","affiliation":[{"name":"Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"Tsao","sequence":"additional","affiliation":[{"name":"Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amir","family":"Horowitz","sequence":"additional","affiliation":[{"name":"Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"},{"name":"Department of Immunology & Immunotherapy, Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"},{"name":"Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8713-3599","authenticated-orcid":false,"given":"Natasha","family":"Kyprianou","sequence":"additional","affiliation":[{"name":"Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"},{"name":"Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"},{"name":"Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Che-Kai","family":"Tsao","sequence":"additional","affiliation":[{"name":"Northwell Cancer Institute, New Hyde Park, New York, NY 11042, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,27]]},"reference":[{"key":"ref_1","first-page":"209","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clinicians."},{"key":"ref_2","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_3","doi-asserted-by":"crossref","unstructured":"Noori, M., Azizi, S., Mahjoubfar, A., Varaki, F.A., Fayyaz, F., Mousavian, A.-H., Bashash, D., Parizi, M.K., and Kasaeian, A. (2023). Efficacy and safety of immune checkpoint inhibitors for patients with prostate cancer: A systematic review and meta-analysis. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1181051"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/s41391-022-00615-5","article-title":"Circulating myeloid-derived suppressor cells and survival in prostate cancer patients: Systematic review and meta-analysis","volume":"26","author":"Bronte","year":"2022","journal-title":"Prostate Cancer Prostatic Diseases"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"956","DOI":"10.3724\/abbs.2023092","article-title":"Advances in landscape and related therapeutic targets of the prostate tumor microenvironment","volume":"55","author":"Li","year":"2023","journal-title":"Acta Biochim. Et Biophys. Sinica"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2451","DOI":"10.1158\/1078-0432.CCR-16-1780","article-title":"Sequencing of Sipuleucel-T and Androgen Deprivation Therapy in Men with Hormone-Sensitive Biochemically Recurrent Prostate Cancer: A Phase II Randomized Trial","volume":"23","author":"Antonarakis","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1038\/s41391-019-0144-3","article-title":"Prolonged PSA stabilization and overall survival following sipuleucel-T monotherapy in metastatic castration-resistant prostate cancer patients","volume":"22","author":"Holl","year":"2019","journal-title":"Prostate Cancer Prostatic Dis."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Meng, L., Yang, Y., Mortazavi, A., and Zhang, J. (2023). Emerging Immunotherapy Approaches for Treating Prostate Cancer. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241814347"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4246","DOI":"10.3390\/curroncol30040323","article-title":"Metastatic Castration-Resistant Prostate Cancer, Immune Checkpoint Inhibitors, and Beyond","volume":"30","author":"Lanka","year":"2023","journal-title":"Curr. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Li, J., Zhang, L., Liu, R., Xu, C., Tang, H., Zou, Y., Cao, Q., and Huang, W. (2025). CXCL12\/CXCR4 Axis Governs Treg Spatial Dominance over CD8+ T Cells via IL-2 sequestration: A Dual Therapeutic Target in Prostate Cancer. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1626708"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1038\/s41698-024-00522-z","article-title":"Targeting M2-like tumor-associated macrophages is a potential therapeutic approach to overcome antitumor drug resistance","volume":"8","author":"Wang","year":"2024","journal-title":"NPJ Precis. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1038\/s41391-024-00825-z","article-title":"Targeting the tumor microenvironment, a new therapeutic approach for prostate cancer","volume":"28","author":"Fang","year":"2024","journal-title":"Prostate Cancer Prostatic Dis."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Bedeschi, M., Marino, N., Cavassi, E., Piccinini, F., and Tesei, A. (2023). Cancer-Associated Fibroblast: Role in Prostate Cancer Progression to Metastatic Disease and Therapeutic Resistance. Cells, 12.","DOI":"10.3390\/cells12050802"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Bonollo, F., Thalmann, G.N., Kruithof-de Julio, M., and Karkampouna, S. (2020). The Role of Cancer-Associated Fibroblasts in Prostate Cancer Tumorigenesis. Cancers, 12.","DOI":"10.3390\/cancers12071887"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12929-024-01099-2","article-title":"Cancer-associated fibroblasts as therapeutic targets for cancer: Advances, challenges, and future prospects","volume":"32","author":"Cao","year":"2025","journal-title":"J. Biomed. Sci."},{"key":"ref_16","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_17","doi-asserted-by":"crossref","first-page":"E182","DOI":"10.1097\/01.JU.0001008572.33286.63.09","article-title":"PD09-09 Role of Tumor Microenvironment Derived NRG1 In Androgen Resistance: Implications for a Novel Prostate Cancer Treatment Strategy","volume":"211","author":"Shinder","year":"2024","journal-title":"J. Urol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3728","DOI":"10.1158\/0008-5472.CAN-24-0932","article-title":"YAP1 Inhibition Induces Phenotype Switching of Cancer-Associated Fibroblasts to Tumor Suppressive in Prostate Cancer","volume":"84","author":"Song","year":"2024","journal-title":"Cancer Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1002\/pros.23948","article-title":"Association between immunosuppressive cytokines and PSA progression in biochemically recurrent prostate cancer treated with intermittent hormonal therapy","volume":"80","author":"Hawley","year":"2020","journal-title":"Prostate"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s12964-019-0505-5","article-title":"Cancer-associated fibroblasts promote prostate tumor growth and progression through upregulation of cholesterol and steroid biosynthesis","volume":"18","author":"Neuwirt","year":"2020","journal-title":"Cell Commun. Signal."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e8347","DOI":"10.15252\/emmm.201708347","article-title":"Sprouty2 loss-induced IL6 drives castration-resistant prostate cancer through scavenger receptor B1","volume":"10","author":"Patel","year":"2018","journal-title":"EMBO Mol. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.ccell.2020.06.005","article-title":"Tumor Microenvironment-Derived NRG1 Promotes Antiandrogen Resistance in Prostate Cancer","volume":"38","author":"Zhang","year":"2020","journal-title":"Cancer Cell."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"6207","DOI":"10.1158\/0008-5472.CAN-21-3360","article-title":"HER3 Is an Actionable Target in Advanced Prostate Cancer","volume":"81","author":"Gil","year":"2021","journal-title":"Cancer Res."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Matos, A., Carvalho, M., Bicho, M., and Ribeiro, R. (2021). Arginine and Arginases Modulate Metabolism, Tumor Microenvironment and Prostate Cancer Progression. Nutrients, 13.","DOI":"10.3390\/nu13124503"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Siemi\u0144ska, I., and Baran, J. (2022). Myeloid-Derived Suppressor Cells as Key Players and Promising Therapy Targets in Prostate Cancer. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.862416"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Koinis, F., Xagara, A., Chantzara, E., Leontopoulou, V., Aidarinis, C., and Kotsakis, A. (2021). Myeloid-Derived Suppressor Cells in Prostate Cancer: Present Knowledge and Future Perspectives. Cells, 11.","DOI":"10.3390\/cells11010020"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.1002\/pros.23885","article-title":"The STAT3 inhibitor galiellalactone inhibits the generation of MDSC-like monocytes by prostate cancer cells and decreases immunosuppressive and tumorigenic factors","volume":"79","author":"Hellsten","year":"2019","journal-title":"Prostate"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s12943-024-02208-3","article-title":"Myeloid-derived Suppressor Cells (MDSCs) in the Tumor Microenvironment and Their Targeting in Cancer Therapy","volume":"24","author":"He","year":"2025","journal-title":"Mol. Cancer"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"109470","DOI":"10.1016\/j.intimp.2022.109470","article-title":"Myeloid-derived Suppressor Cells (MDSCs) Depletion by Cabozantinib Improves the Efficacy of anti-HER2 antibody-based Immunotherapy in a 4T1-HER2 Murine Breast Cancer Model","volume":"113","author":"Bakhtiarvand","year":"2022","journal-title":"Int. Immunopharmacol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s40164-024-00505-7","article-title":"Myeloid-derived suppressor cells in cancer: Therapeutic targets to overcome tumor immune evasion","volume":"13","author":"Lu","year":"2024","journal-title":"Exp. Hematol. Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/S1535-6108(03)00215-0","article-title":"Prostate-specific deletion of the murine Pten tumor suppressor gene leads to metastatic prostate cancer","volume":"4","author":"Wang","year":"2003","journal-title":"Cancer Cell"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Gu, Q., Qi, A., Wang, N., Zhou, Z., and Zhou, X. (2024). Macrophage dynamics in prostate cancer: Molecular to therapeutic insights. Biomed. Pharmacother., 177.","DOI":"10.1016\/j.biopha.2024.117002"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1038\/s41419-020-2435-y","article-title":"CCL5 derived from tumor-associated macrophages promotes prostate cancer stem cells and metastasis via activating \u03b2-catenin\/STAT3 signaling","volume":"11","author":"Huang","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2054","DOI":"10.1002\/cbin.11630","article-title":"Tumor-associated macrophage-derived CCL5 promotes chemotherapy resistance and metastasis in prostatic cancer","volume":"45","author":"Ma","year":"2021","journal-title":"Cell Biol. Int."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Anton, A., Hutchinson, R., Hovens, C.M., Christie, M., Ryan, A., Gibbs, P., Costello, A., Peters, J., Neeson, P.J., and Corcoran, N.M. (2024). An immune suppressive tumor microenvironment in primary prostate cancer promotes tumor immune escape. Nie D, ed. PLoS ONE, 19.","DOI":"10.1371\/journal.pone.0301943"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Palicelli, A., Croci, S., Bisagni, A., Zanetti, E., De Biase, D., Melli, B., Sanguedolce, F., Ragazzi, M., Zanelli, M., and Chaux, A. (2021). What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 5: Epigenetic Regulation of PD-L1. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222212314"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1958","DOI":"10.1016\/j.ymthe.2021.04.029","article-title":"The roles of PD-1\/PD-L1 in the prognosis and immunotherapy of prostate cancer","volume":"29","author":"Xu","year":"2021","journal-title":"Mol. Ther."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1038\/nrc3223","article-title":"Unmasking the Immune Recognition of Prostate Cancer with CTLA4 Blockade","volume":"12","author":"Kwek","year":"2012","journal-title":"Nat. Rev. Cancer"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Seidel, J.A., Otsuka, A., and Kabashima, K. (2018). Anti-PD-1 and Anti-CTLA-4 Therapies in Cancer: Mechanisms of Action, Efficacy, and Limitations. Front. Oncol., 8.","DOI":"10.3389\/fonc.2018.00086"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1016\/j.immuni.2016.05.002","article-title":"Coinhibitory Pathways in the B7-CD28 Ligand-Receptor Family","volume":"44","year":"2016","journal-title":"Immunity"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Chetta, P., Sriram, R., and Zadra, G. (2023). Lactate as Key Metabolite in Prostate Cancer Progression: What Are the Clinical Implications?. Cancers, 15.","DOI":"10.3390\/cancers15133473"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1007\/s12551-020-00758-6","article-title":"Metabolism of Prostate Cancer by Magnetic Resonance Spectroscopy (MRS)","volume":"12","author":"Sharma","year":"2020","journal-title":"Biophys. Rev."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"109674","DOI":"10.1016\/j.isci.2024.109674","article-title":"Cancer-associated fibroblasts promote enzalutamide resistance and PD-L1 expression in prostate cancer through CCL5-CCR5 paracrine axis","volume":"27","author":"Xiong","year":"2024","journal-title":"iScience"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1615\/CritRevOncog.2022043478","article-title":"Novel Therapeutic Targets and Biomarkers Associated with Prostate Cancer-Associated Fibroblasts (CAFs)","volume":"27","author":"Clark","year":"2022","journal-title":"Crit. Rev. Oncog."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1038\/s41586-018-0266-0","article-title":"IL-23 secreted by myeloid cells drives castration-resistant prostate cancer","volume":"559","author":"Calcinotto","year":"2018","journal-title":"Nature"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"TPS5105","DOI":"10.1200\/JCO.2023.41.16_suppl.TPS5105","article-title":"A phase (Ph) I\/II trial of abiraterone acetate in combination with tildrakizumab (anti-IL23 monoclonal antibody) in patients with metastatic castration-resistant prostate cancer (mCRPC)","volume":"41","author":"Guo","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Guan, W., Li, F., Zhao, Z., Zhang, Z., Hu, J., and Zhang, Y. (2021). Tumor-Associated Macrophage Promotes the Survival of Cancer Cells upon Docetaxel Chemotherapy via the CSF1\/CSF1R-CXCL12\/CXCR4 Axis in Castration-Resistant Prostate Cancer. Genes, 12.","DOI":"10.3390\/genes12050773"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1186\/s12943-019-1022-2","article-title":"Targeting Tyro3, Axl and MerTK (TAM receptors): Implications for Macrophages in the Tumor Microenvironment","volume":"18","author":"Myers","year":"2019","journal-title":"Mol. Cancer"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1952","DOI":"10.1158\/1078-0432.CCR-22-3350","article-title":"Reversal of lactate and PD-1-mediated macrophage immunosuppression controls growth of PTEN\/p53-deficient prostate cancer","volume":"29","author":"Chaudagar","year":"2023","journal-title":"Clin. Cancer Res."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Che, J., Liu, Y., Liu, Y., Song, J., Cui, H., Feng, D., Tian, A., Zhang, Z., and Xu, Y. (2025). The application of emerging immunotherapy in the treatment of prostate cancer: Progress, dilemma and promise. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1544882"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e001065","DOI":"10.1136\/jitc-2020-001065","article-title":"Clinical activity of pembrolizumab in metastatic prostate cancer with microsatellite instability high (MSI-H) detected by circulating tumor DNA","volume":"8","author":"Barata","year":"2020","journal-title":"J. Immunother. Cancer"},{"key":"ref_52","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_53","doi-asserted-by":"crossref","first-page":"4965","DOI":"10.7150\/thno.73152","article-title":"Docetaxel remodels prostate cancer immune microenvironment and enhances checkpoint inhibitor-based immunotherapy","volume":"12","author":"Ma","year":"2022","journal-title":"Theranostics"},{"key":"ref_54","first-page":"87","article-title":"A randomized, phase II study of pazopanib in castrate-sensitive prostate cancer: A University of Chicago Phase II Consortium\/Department of Defense Prostate Cancer Clinical Trials Consortium study","volume":"15","author":"Karrison","year":"2011","journal-title":"Prostate Cancer Prostatic Dis."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Agarwal, N., Azad, A., Carles, J., Matsubara, N., Oudard, S., Saad, F., Merseburger, A.S., Soares, A., McGregor, B.A., and Zurawski, B. (2024). CONTACT-02: Phase 3 study of cabozantinib (C) plus atezolizumab (A) vs second novel hormonal therapy (NHT) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC). J. Clin. Oncol., 42.","DOI":"10.1200\/JCO.2024.42.4_suppl.18"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"102336","DOI":"10.1016\/j.clgc.2025.102336","article-title":"Characterization of exceptional responses in patients with metastatic castration-resistant prostate cancer treated with cabozantinib and immune checkpoint inhibitors","volume":"23","author":"Ganta","year":"2025","journal-title":"Clin. Genitourin. Cancer"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e41379","DOI":"10.1097\/MD.0000000000041379","article-title":"Role of the AKT signaling pathway in regulating tumor-associated macrophage polarization and in the tumor microenvironment: A review","volume":"104","author":"Liang","year":"2025","journal-title":"Medicine"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"102244","DOI":"10.1016\/j.clgc.2024.102244","article-title":"Efficacy and Safety of Combination AKT and Androgen Receptor Signaling Inhibition in Metastatic Castration-Resistant Prostate Cancer: Systematic Review and Meta-Analysis","volume":"22","author":"Nahar","year":"2024","journal-title":"Clin. Genitourin. Cancer"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"eadq3802","DOI":"10.1126\/sciadv.adq3802","article-title":"Uncoupling of Akt and mTOR signaling drives resistance to Akt inhibition in PTEN loss prostate cancers","volume":"11","author":"Mao","year":"2025","journal-title":"Sci. Adv."},{"key":"ref_60","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":"2022","journal-title":"J. Cell Commun. Signal."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1038\/s41416-024-02614-w","article-title":"Capivasertib Combines with Docetaxel to Enhance anti-tumour Activity through Inhibition of AKT-mediated Survival Mechanisms in Prostate Cancer","volume":"130","author":"Eberlein","year":"2024","journal-title":"Br. J. Cancer"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1016\/j.semcancer.2022.04.003","article-title":"Radiation therapy-induced Remodeling of the Tumor Immune Microenvironment","volume":"86","author":"Charpentier","year":"2022","journal-title":"Semin. Cancer Biol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1056\/NEJMoa2107322","article-title":"Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer","volume":"385","author":"Sartor","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"LBA4","DOI":"10.1200\/JCO.2021.39.15_suppl.LBA4","article-title":"Phase III study of lutetium-177-PSMA-617 in patients with metastatic castration-resistant prostate cancer (VISION)","volume":"39","author":"Morris","year":"2021","journal-title":"J. Clin. Oncol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"175883592311576","DOI":"10.1177\/17588359231157632","article-title":"Status of PSMA-targeted Radioligand Therapy in Prostate Cancer: Current Data and Future Trials","volume":"15","author":"Jang","year":"2023","journal-title":"Ther. Adv. Med. Oncol."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Inoue, T., Sho Sekito Kageyama, T., Sugino, Y., and Sasaki, T. (2023). Roles of the PARP Inhibitor in BRCA1 and BRCA2 Pathogenic Mutated Metastatic Prostate Cancer: Direct Functions and Modification of the Tumor Microenvironment. Cancers, 15.","DOI":"10.3390\/cancers15092662"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/S1470-2045(19)30684-9","article-title":"Olaparib in patients with metastatic castration-resistant prostate cancer with DNA repair gene aberrations (TOPARP-B): A multicentre, open-label, randomized, phase 2 trial","volume":"21","author":"Mateo","year":"2020","journal-title":"Lancet Oncol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.eururo.2023.05.021","article-title":"Rucaparib for the Treatment of Metastatic Castration-resistant Prostate Cancer Associated with a DNA Damage Repair Gene Alteration: Final Results from the Phase 2 TRITON2 Study","volume":"84","author":"Abida","year":"2023","journal-title":"Eur. Urol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1056\/NEJMoa2214676","article-title":"Rucaparib or Physician\u2019s Choice in Metastatic Prostate Cancer","volume":"388","author":"Fizazi","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1053\/j.seminoncol.2023.09.003","article-title":"PARP Inhibitors for Prostate Cancer","volume":"51","author":"Longoria","year":"2023","journal-title":"Semin. Oncol."},{"key":"ref_71","first-page":"1","article-title":"Development of PARP Inhibitors in Advanced Prostate Cancer","volume":"16","author":"Castro","year":"2024","journal-title":"Ther. Adv. Med. Oncol."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Pei, X., Liu, L., and Han, Y. (2025). Advances in Human Microbiome and Prostate Cancer Research. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1576679"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Kustrimovic, N., Bombelli, R., Baci, D., and Mortara, L. (2023). Microbiome and Prostate Cancer: A Novel Target for Prevention and Treatment. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24021511"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.jare.2023.11.027","article-title":"The Role of Gut Microbiota and Metabolites in Cancer Chemotherapy","volume":"64","author":"Li","year":"2023","journal-title":"J. Adv. Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"e70294","DOI":"10.1002\/cam4.70294","article-title":"Immunotherapy Vaccines for Prostate Cancer Treatment","volume":"13","author":"He","year":"2024","journal-title":"Cancer Med."},{"key":"ref_76","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_77","doi-asserted-by":"crossref","first-page":"110486","DOI":"10.1016\/j.isci.2024.110486","article-title":"Applications of single-cell Technologies in Drug Discovery for Tumor Treatment","volume":"27","author":"Liu","year":"2024","journal-title":"iScience"},{"key":"ref_78","first-page":"1","article-title":"The implications of single-cell RNA-seq analysis in prostate cancer: Unraveling tumor heterogeneity, therapeutic implications and pathways towards personalized therapy","volume":"11","author":"Feng","year":"2024","journal-title":"Mil. Med. Res."},{"key":"ref_79","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_80","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1186\/s13045-021-01105-2","article-title":"Applications of single-cell sequencing in cancer research: Progress and perspectives","volume":"14","author":"Lei","year":"2021","journal-title":"J. Hematol. Oncol."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/21\/3441\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T17:15:27Z","timestamp":1761671727000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/21\/3441"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,27]]},"references-count":80,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["cancers17213441"],"URL":"https:\/\/doi.org\/10.3390\/cancers17213441","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,27]]}}}