biostudies-literatureLiukaityte RKreftforeningenResearch Council of FinlandThe European Union's Horizon 2020 research and innovation programmeThe European Union’s Horizon 2020 research and innovation programmeUniversity of OsloARTBIO, NorwayRadforsk, Oslo, Norway362https://www.ebi.ac.uk/biostudies/studies/S-EPMC12283873biostudies-literatureUnknown42(8)The alpha-emitting radioligand [²¹²Pb]Pb-AB001, targeting prostate-specific membrane antigen (PSMA), is a promising therapy approach for prostate cancer. Bromodomain and extra-terminal (BET) protein inhibitors, such as AZD5153 and JQ1, disrupt oncogenic transcriptional programs by altering chromatin structure. This study evaluated whether BET inhibition enhances the efficacy of radioligand therapy. Cytotoxic effects of [²¹²Pb]Pb-AB001 alone and in combination with BET inhibitors were assessed in 2D monolayers and a 3D spheroid model of PSMA-positive C4-2 prostate cancer cells. Cell viability, cell cycle alterations, and DNA damage were assessed using viability assays and flow cytometry. Spheroid growth and viability were assessed by fluorescence microscopy. AZD5153 waMedical oncology (Northwood, London, England)Combination of PSMA targeting alpha-emitting radioligand [<sup>212</sup>Pb]Pb-AB001 with BET bromodomain inhibitors in in vitro prostate cancer models.PMC12283873349314273672 & 198016No 101008571 (PRISMAP)273672 & 198016TARACANStenberg VYJuzeniene ALiukaityte RJuzenas PKleinauskas AUrbanucci AfalseCombination of PSMA targeting alpha-emitting radioligand [<sup>212</sup>Pb]Pb-AB001 with BET bromodomain inhibitors in in vitro prostate cancer models.The alpha-emitting radioligand [²¹²Pb]Pb-AB001, targeting prostate-specific membrane antigen (PSMA), is a promising therapy approach for prostate cancer. Bromodomain and extra-terminal (BET) protein inhibitors, such as AZD5153 and JQ1, disrupt oncogenic transcriptional programs by altering chromatin structure. This study evaluated whether BET inhibition enhances the efficacy of radioligand therapy. Cytotoxic effects of [²¹²Pb]Pb-AB001 alone and in combination with BET inhibitors were assessed in 2D monolayers and a 3D spheroid model of PSMA-positive C4-2 prostate cancer cells. Cell viability, cell cycle alterations, and DNA damage were assessed using viability assays and flow cytometry. Spheroid growth and viability were assessed by fluorescence microscopy. AZD5153 wa2025-01-01T00:00:00Z2025 Jul2026-03-16T06:29:26.57Z2025-08-14T03:06:30.214ZS-EPMC122838734069418410.1007/s12032-025-02925-9