{"doi":"10.1371/journal.pone.0214670","title":"Radiosensitization by enzalutamide for human prostate cancer is mediated through the DNA damage repair pathway","abstract":null,"journal":"PLOS ONE","year":2019,"id":628556,"datarank":0.5495342469194471,"base_score":3.6635616461296463,"endowment":3.6635616461296463,"self_citation_contribution":0.5495342469194471,"citation_network_contribution":0.0,"self_endowment_contribution":0.5495342469194471,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":38,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1347684,"name":"Jian Wang","orcid":"0000-0001-5184-7023","position":1,"is_corresponding":false},{"id":824130,"name":"Michael L. Freeman","orcid":"0000-0003-1881-366X","position":2,"is_corresponding":false},{"id":371540,"name":"Austin N. Kirschner","orcid":"0000-0003-3807-6900","position":3,"is_corresponding":false},{"id":414590,"name":"Konjeti R. Sekhar","orcid":"0000-0003-2930-0739","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Radiosensitization by enzalutamide for human prostate cancer is mediated through the DNA damage repair pathway","abstract":"Radiation therapy is often combined with androgen deprivation therapy in the treatment of aggressive localized prostate cancer. However, castration-resistant disease may not respond to testosterone deprivation approaches. Enzalutamide is a second-generation anti-androgen with high affinity and activity that is used for the treatment of metastatic disease. Although radiosensitization mechanisms are known to be mediated through androgen receptor activity, this project aims to uncover the detailed DNA damage repair factors influenced by enzalutamide using multiple models of androgen-sensitive (LNCaP) and castration-resistant human prostate cancer (22Rv1 and DU145). Enzalutamide is able to radiosensitize both androgen-dependent and androgen-independent human prostate cancer models in cell culture and xenografts in mice, as well as a treatment-resistant patient-derived xenograft. The enzalutamide-mediated mechanism of radiosensitization includes delay of DNA repair through temporal prolongation of the repair factor complexes and halting the cell cycle, which results in decreased colony survival. Altogether, these findings support the use of enzalutamide concurrently with radiotherapy to enhance the treatment efficacy for prostate cancer.","is_dataset_classified":null,"base_score":3.6635616461296463,"endowment":3.6635616461296463,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"30933998","pmcid":"PMC6443157","openalex_id":"https://openalex.org/W2931472946","authors":[],"funders":[{"funder_name":"Astellas Pharma US","grant_id":"ENZA-15C03","title":null},{"funder_name":"Vanderbilt University Medical Center","grant_id":"5K12CA090625-18","title":"Vanderbilt Clinical Oncology Research Career Development Award"},{"funder_name":"NIDDK NIH HHS","grant_id":"U24 DK059637","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"P30 DK058404","title":null},{"funder_name":"NCI NIH HHS","grant_id":"K12 CA090625","title":null},{"funder_name":"NIH HHS","grant_id":"S10 OD023475","title":null},{"funder_name":"NCI NIH HHS","grant_id":"P30 CA068485","title":null},{"funder_name":"National Institutes of Health","grant_id":"3P30CA068485-23S2","title":"Cancer Center Support Grant"},{"funder_name":"National Institutes of Health","grant_id":"3P30CA068485-21S4","title":"Cancer Center Support Grant"},{"funder_name":"National Institutes of Health","grant_id":"5U24DK059637-13","title":"Vanderbilt Mouse Metabolic Phenotyping Center"}],"total_grants":10,"fwci":3.4771,"citation_percentile":0.93634591,"influential_citations":0,"citation_trend":[{"year":2019,"count":3},{"year":2020,"count":7},{"year":2021,"count":7},{"year":2022,"count":6},{"year":2023,"count":5},{"year":2024,"count":4},{"year":2025,"count":4},{"year":2026,"count":2}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0214670&type=printable","host_type":"journal"},{"url":"https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0214670&type=printable","host_type":"publisher"},{"url":"http://dx.plos.org/10.1371/journal.pone.0214670","host_type":"publisher"},{"url":"https://doi.org/10.1371/journal.pone.0214670","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/30933998","host_type":"repository"},{"url":"https://doaj.org/article/c2a8a8b5fcbf4569a497866831a60e06","host_type":"repository"},{"url":"https://figshare.com/articles/dataset/Radiosensitization_by_enzalutamide_for_human_prostate_cancer_is_mediated_through_the_DNA_damage_repair_pathway/7933073","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/6443157","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC6443157","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC6443157?pdf=render","host_type":"Europe_PMC"},{"url":"http://dx.doi.org/10.1371/journal.pone.0214670","host_type":""},{"url":"https://dx.doi.org/10.1371/journal.pone.0214670","host_type":""}],"fields_of_study":["Prostate Cancer Treatment and Research","DNA Repair Mechanisms","PARP inhibition in cancer therapy","0301 basic medicine","03 medical and health sciences","0303 health sciences"],"mesh_terms":["Aged","Animals","Benzamides","DNA Damage","DNA Repair","Humans","Male","Mice, Nude","Mice, Transgenic","Nitriles","Phenylthiohydantoin","Prostatic Neoplasms","Radiation Tolerance","Radiation-Sensitizing Agents","Signal Transduction","Drug Resistance, Neoplasm","Xenograft Model Antitumor Assays","Cell Line, Tumor","Cell Proliferation","Mice","Prostatic Neoplasms, Castration-Resistant"],"keywords":["Enzalutamide","DU145","Prostate cancer","LNCaP","Medicine","Androgen receptor","Cancer research","Androgen deprivation therapy","Androgen","DNA repair","Cancer","Internal medicine","Radiation therapy","Oncology","Biology","DNA","Hormone","Genetics","Male","Radiation-Sensitizing Agents","Science","Mice, Nude","Mice, Transgenic","Radiation Tolerance","Mice","Cell Line, Tumor","Nitriles","Phenylthiohydantoin","Animals","Humans","Aged","Cell Proliferation","Q","R","Prostatic Neoplasms","Prostatic Neoplasms, Castration-Resistant","Drug Resistance, Neoplasm","Benzamides","Research Article","DNA Damage","Signal Transduction"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. 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