biostudies-arrayexpressMetabolomicsUnknownTranscriptomicsGenomicsProteomicsGiada SandriniNextSeq 500ATAC-seqHomo sapiensHomo sapienshttps://www.ebi.ac.uk/biostudies/studies/E-MTAB-12986The rewiring of transcriptional and epigenetic programs is a hallmark of cancer and a targetable vulnerability for treating metastatic cancers. CDK9, whose primary function is to promote transcriptional elongation at active gene promoters, is emerging as a therapeutic target with broad efficacy in various cancer types. We used the novel and selective CDK9 inhibitor PRT2527 to demonstrate this approach's therapeutic efficacy and tolerability in multiple preclinical tumor models with specific transcriptional dependencies. In castration-resistant prostate cancer (CRPC), PRT2527 inhibited CDK9, AR and other transcription factors (e.g., c-MYC, STAT3, and NF-B) implicated in disease progression and treatment resistance. PRT2527 reduced the proliferation of tumor cell lines and the growth of 3D tumor organoids and spheroids, demonstrating the impact on the bulk tumor cells and the stem-like subpopulation in human and murine CRPC models. PRT2527 was also highly active in vivo in patient-derived CRPC models LuCaP 35 and LuCap 145.2) and transgenic Pb-Cre4;Ptenflox/flox;R26ERG (ERG/PTEN) mice. Notably, PRT2527 induced relevant changes in gene expression, reflecting the impact on the distinct transcriptional programs of various CRPC models. Despite this heterogeneity, a common core of genes and pathways related to oncogenesis was affected in all models. Our data further demonstrate the efficacy and safety of CDK9 inhibition in multiple models of transcriptionally addicted solid tumors. Given its role in transcription, CDK9 is an ideal target for developing novel therapeutic strategies to block tumor cell plasticity driving tumor progression, metastatic spread, and treatment resistance.biostudies-arrayexpressNucleic Acid Extraction - - Resuspension of nuclei in the transposition reaction mix- Incubation of the transposition reaction- Purification using Qiagen MinElute PCR Purification Kit- Elution of transposed DNA in Elution BufferRefer to DOI: 10.1002/0471142727.mb2129s109Library Construction - - Amplification of DNA fragments- Purification of amplified library using Qiagen MinElute PCR Purification KitSequencing - Illumina NextSeq500Sample Collection - Collection of 50000 cells per replicate and resuspension of the pellet in TRIzol bufferOrganizationMINSEQE ScoreAssays and DataMAGE-TAB FilesCarlo CatapanoMarco BolisElisa FedericiGiada SandriniLuca GuarrerafalseATAC-seq to investigate rewiring the transcriptome of castration-resistant prostate cancer through CDK9 inhibition dataset 1The rewiring of transcriptional and epigenetic programs is a hallmark of cancer and a targetable vulnerability for treating metastatic cancers. CDK9, whose primary function is to promote transcriptional elongation at active gene promoters, is emerging as a therapeutic target with broad efficacy in various cancer types. We used the novel and selective CDK9 inhibitor PRT2527 to demonstrate this approach's therapeutic efficacy and tolerability in multiple preclinical tumor models with specific transcriptional dependencies. In castration-resistant prostate cancer (CRPC), PRT2527 inhibited CDK9, AR and other transcription factors (e.g., c-MYC, STAT3, and NF-B) implicated in disease progression and treatment resistance. PRT2527 reduced the proliferation of tumor cell lines and the growth of 3D tumor organoids and spheroids, demonstrating the impact on the bulk tumor cells and the stem-like subpopulation in human and murine CRPC models. PRT2527 was also highly active in vivo in patient-derived CRPC models LuCaP 35 and LuCap 145.2) and transgenic Pb-Cre4;Ptenflox/flox;R26ERG (ERG/PTEN) mice. Notably, PRT2527 induced relevant changes in gene expression, reflecting the impact on the distinct transcriptional programs of various CRPC models. Despite this heterogeneity, a common core of genes and pathways related to oncogenesis was affected in all models. Our data further demonstrate the efficacy and safety of CDK9 inhibition in multiple models of transcriptionally addicted solid tumors. Given its role in transcription, CDK9 is an ideal target for developing novel therapeutic strategies to block tumor cell plasticity driving tumor progression, metastatic spread, and treatment resistance.2026-04-08T00:00:00Z2026-04-09T01:02:08.764Z2023-05-23T12:59:33.417ZE-MTAB-12986ERP147611E-MTAB-12987EFO_0002944EFO_0007045EFO_0004170EFO_0005518EFO_0004184