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Despite existing treatments, 10\u201320% of patients eventually progress to metastatic castration-resistant disease (mCRPC). The median overall survival (OS) after progression to mCPRC drops to 24 months, and efficacy drops severely after each additional line of treatment. Omics platforms have reached advanced levels and enable the acquisition of high-resolution large datasets that can provide insights into the molecular mechanisms underlying PCa pathology. Genomics, especially DDR (DNA damage response) gene alterations, detected via tissue and\/or circulating tumor DNA, efficiently guides therapy in advanced prostate cancer. Given recent developments, we have performed a comprehensive literature search to cover recent research and clinical trial reports (over the last five years) that integrate omics along three converging trajectories in therapeutic development: (i) predicting response to approved agents with demonstrated survival benefits, (ii) stratifying patients to receive therapies in clinical trials, (iii) guiding drug development as part of drug repurposing frameworks. Collectively, this review is intended to serve as a comprehensive resource of recent advancements in omics-guided therapies for advanced prostate cancer, a clinical setting with existing clinical needs and poor outcomes.<\/jats:p>","DOI":"10.3390\/ijms26157475","type":"journal-article","created":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T15:56:16Z","timestamp":1754409376000},"page":"7475","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Omics-Mediated Treatment for Advanced Prostate Cancer: Moving Towards Precision Oncology"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7386-4246","authenticated-orcid":false,"given":"Yasra","family":"Fatima","sequence":"first","affiliation":[{"name":"Department of Biomarker Research, Mosaiques Diagnostics GmbH, 30659 Hannover, Germany"},{"name":"Institute for Molecular Cardiovascular Research (IMCAR), RWTH Aachen University, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5548-049X","authenticated-orcid":false,"given":"Kirubel Nigusu","family":"Jobre","sequence":"additional","affiliation":[{"name":"Department of Biomarker Research, Mosaiques Diagnostics GmbH, 30659 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8753-3306","authenticated-orcid":false,"given":"Enrique","family":"Gomez-Gomez","sequence":"additional","affiliation":[{"name":"Urology Department, Reina Sof\u00eda University Hospital, Maimonides Institute of Biomedical Research of Cordoba (IMIBIC), University of Cordoba (UCO), 14004 Cordoba, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5933-3753","authenticated-orcid":false,"given":"Bartosz","family":"Ma\u0142kiewicz","sequence":"additional","affiliation":[{"name":"Department of Minimally Invasive and Robotic Urology, Centre of Excellence in Urology, Wroclaw Medical University, 213 Borowska Street, 50-556 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3284-5713","authenticated-orcid":false,"given":"Antonia","family":"Vlahou","sequence":"additional","affiliation":[{"name":"Systems Biology Center, Biomedical Research Foundation, Academy of Athens, 115 27 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4511-1578","authenticated-orcid":false,"given":"Marika","family":"Mokou","sequence":"additional","affiliation":[{"name":"Department of Biomarker Research, Mosaiques Diagnostics GmbH, 30659 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0323-0306","authenticated-orcid":false,"given":"Harald","family":"Mischak","sequence":"additional","affiliation":[{"name":"Department of Biomarker Research, Mosaiques Diagnostics GmbH, 30659 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0415-0316","authenticated-orcid":false,"given":"Maria","family":"Frantzi","sequence":"additional","affiliation":[{"name":"Department of Biomarker Research, Mosaiques Diagnostics GmbH, 30659 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6416-0230","authenticated-orcid":false,"given":"Vera","family":"Jankowski","sequence":"additional","affiliation":[{"name":"Institute for Molecular Cardiovascular Research (IMCAR), RWTH Aachen University, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,2]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global Cancer Statistics 2022: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA. 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