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However, the ability to effectively evaluate the drug's efficacy remains a challenge. Impediments to broad applicability include inaccuracies in many of the computational drug\u2010target algorithms and a lack of clinically relevant biologic modeling systems to validate the computational data for subsequent translation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We have integrated our computational proteochemometric systems network pharmacology platform, DrugGenEx\u2010Net, with primary, continuous cultures of conditionally reprogrammed (CR) normal and prostate cancer (PCa) cells derived from treatment\u2010naive patients with primary PCa.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Using the transcriptomic data from two matched pairs of benign and tumor\u2010derived CR cells, we constructed drug networks to describe the biological perturbation associated with each prostate cell subtype at multiple levels of biological action. We prioritized the drugs by analyzing these networks for statistical coincidence with the drug action networks originating from known and predicted drug\u2010protein targets. Prioritized drugs shared between the two patients\u2019 PCa cells included carfilzomib (CFZ), bortezomib (BTZ), sulforaphane, and phenethyl isothiocyanate. The effects of these compounds were then tested in the CR cells, in vitro. We observed that the IC<jats:sub>50<\/jats:sub> values of the normal PCa CR cells for CFZ and BTZ were higher than their matched tumor CR cells. Transcriptomic analysis of CFZ\u2010treated CR cells revealed that genes involved in cell proliferation, proteases, and downstream targets of serine proteases were inhibited while <jats:italic>KLK7<\/jats:italic> and <jats:italic>KLK8<\/jats:italic> were induced in the tumor\u2010derived CR cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Given that the drugs in the database are extremely well\u2010characterized and that the patient\u2010derived cells are easily scalable for high throughput drug screening, this combined in vitro and in silico approach may significantly advance personalized PCa treatment and for other cancer applications.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pros.24050","type":"journal-article","created":{"date-parts":[[2020,8,6]],"date-time":"2020-08-06T23:58:45Z","timestamp":1596758325000},"page":"1233-1243","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Predicting new drug indications for prostate cancer: The integration of an in silico proteochemometric network pharmacology platform with patient\u2010derived primary prostate cells"],"prefix":"10.1002","volume":"80","author":[{"given":"Aisha","family":"Naeem","sequence":"first","affiliation":[{"name":"Department of Oncology, Lombardi Comprehensive Cancer Center Georgetown University Medical Center  Washington DC"},{"name":"Ministry of Public Health  Doha Qatar"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sivanesan","family":"Dakshanamurthy","sequence":"additional","affiliation":[{"name":"Department of Oncology, Lombardi Comprehensive Cancer Center Georgetown University Medical Center  Washington DC"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henry","family":"Walthieu","sequence":"additional","affiliation":[{"name":"Department of Oncology, Lombardi Comprehensive Cancer Center Georgetown University Medical Center  Washington DC"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erika","family":"Parasido","sequence":"additional","affiliation":[{"name":"Department of Oncology, Lombardi Comprehensive Cancer Center Georgetown University Medical Center  Washington DC"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Avantaggiati","sequence":"additional","affiliation":[{"name":"Department of Oncology, Lombardi Comprehensive Cancer Center Georgetown University Medical Center  Washington DC"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucas","family":"Tricoli","sequence":"additional","affiliation":[{"name":"Julius L. Chambers Biomedical\/Biotechnology Research Institute North Carolina Central University  Durham North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deepak","family":"Kumar","sequence":"additional","affiliation":[{"name":"Julius L. Chambers Biomedical\/Biotechnology Research Institute North Carolina Central University  Durham North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard J.","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Medicine Massachusetts General Hospital Cancer Center  Boston Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam","family":"Feldman","sequence":"additional","affiliation":[{"name":"Department of Medicine Massachusetts General Hospital Cancer Center  Boston Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muhammad S.","family":"Noon","sequence":"additional","affiliation":[{"name":"Data Science Institute University of Arizona  Tuscon Arizona"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen","family":"Byers","sequence":"additional","affiliation":[{"name":"Department of Oncology, Lombardi Comprehensive Cancer Center Georgetown University Medical Center  Washington DC"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olga","family":"Rodriguez","sequence":"additional","affiliation":[{"name":"Department of Oncology, Lombardi Comprehensive Cancer Center Georgetown University Medical Center  Washington DC"},{"name":"Center for Translational Imaging Georgetown University Medical Center  Washington DC"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3072-2373","authenticated-orcid":false,"given":"Chris","family":"Albanese","sequence":"additional","affiliation":[{"name":"Department of Oncology, Lombardi Comprehensive Cancer Center Georgetown University Medical Center  Washington DC"},{"name":"Center for Translational Imaging Georgetown University Medical Center  Washington DC"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,8,6]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2018.11716"},{"issue":"2","key":"e_1_2_9_3_1","first-page":"111","article-title":"Prostate cancer in elderly men","volume":"10","author":"Stangelberger A","year":"2008","journal-title":"Rev Urol"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-16-1780"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdy072"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2017.10.002"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.2174\/1386207318666150803130138"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12859-016-1065-y"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.21669"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.14990"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.2528"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2011.10.036"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.1849"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.13937"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.23363"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1517\/13543780903002074"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10637-014-0189-z"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(18)30354-1"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-19-0191"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2013.08.009"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2689"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkn580"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm300576q"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkn698"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkm415"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku1003"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bth449"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.2144\/mar03dudoit"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-9877(95)90228-7"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1038"},{"key":"e_1_2_9_31_1","unstructured":"OliverosJC.VENNY. 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