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Oncol."],"abstract":"<jats:p>The treatment of castration-resistant prostate cancer (CRPC) remains challenging due to the failure of androgen deprivation therapy (ADT); hence the search for other molecular therapeutic targets besides androgen receptor signaling is ongoing. This study systematically investigated the expression of SOX17 and Notch receptors in CRPC tissues and cells <jats:italic>in vitro<\/jats:italic>, showing that consistent clinical CRPC, SOX17\/Notch1, and Notch4 were responsible for enzalutamide resistance in CRPC cells. The <jats:italic>\u03b3<\/jats:italic> secretase inhibitors, BMS-708163, GSI-IX, PF-3084014, and RO4929097 abrogated the enzalutamide resistance by inhibiting Notch1 or\/and Notch4 <jats:italic>in vitro<\/jats:italic>, with GSI-IX and RO4929097 being more effective than BMS-708163 and PF-3084014 in reliving bone metastasis <jats:italic>in vivo<\/jats:italic>. In conclusion, the Notch1 and Notch4 inhibitors GSI-IX and RO4929097 are promising therapeutic agents for the treatment of CRPC.<\/jats:p>","DOI":"10.3389\/fonc.2021.607291","type":"journal-article","created":{"date-parts":[[2021,3,10]],"date-time":"2021-03-10T05:53:54Z","timestamp":1615355634000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Systematic Evaluation for the Influences of the SOX17\/Notch Receptor Family Members on Reversing Enzalutamide Resistance in Castration-Resistant Prostate Cancer 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