GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE279nnn/GSE279011/primary200OKTranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE279011GEOGSEfalseTargeted Delivery of Selective BET InhibitorsThe circumvention of tissue-specific toxicity while improving selectivity remains a significant challenge in cancer therapy. Antibody-assisted delivery of chemotypes aims to address this, leading to several approved therapies; however, non-specific payload release and poor solid tumour penetration necessitate alternative approaches. To this end, we engineered a ligand-targeted drug conjugate, exploiting the over-expression of the prostate-specific membrane antigen (PSMA) in prostate cancer to selectively deliver and conditionally release RT53, a highly specific epigenetic inhibitor of the bromo and extra-terminal (BET) proteins. RT53 phenocopies the effects of the well characterized IBET pan-BET inhibitor in vitro and in vivo, arresting cellular growth and downregulating solute carriers, while exhibiting antitumor activity in subcutaneous ectopic prostate cancer mouse models. Importantly, PSMA-targeted delivery and conditional release of RT53 achieves superior efficacy in vivo ameliorating on-target, off-tissue toxicity, and establishing proof-of-concept for the targeted delivery of small molecule epigenetic chemotherapeutics.2026/08/27GSE279011GSM8559619GSM8559626GSM8559637GSM8559627GSM8559638GSM8559639GSM8559628GSM8559629GSM8559633GSM8559622GSM8559634GSM8559623GSM8559624GSM8559635GSM8559636GSM8559625GSM8559640GSM8559630GSM8559641GSM8559631GSM8559642GSM8559620GSM8559621GSM855963218573279011Homo sapiens