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The following is a summary of “Patient-derived castration-resistant prostate cancer model revealed CTBP2 upregulation mediated by OCT1 and androgen receptor,” published in the May 2024 issue of Oncology by Obinata et al.
Prostate cancer is initially driven by androgen receptor (AR) signaling, and androgen deprivation therapy (ADT) remains effective in its treatment. However, the emergence of castration-resistant prostate cancer (CRPC) presents a significant challenge. Despite the use of AR signaling inhibitors (ARSI), resistance often develops due to genetic alterations in AR and epigenetic changes.
In this study, researchers investigated the role of OCT1, a member of the OCT family, in a patient with an AR-positive CRPC-derived xenograft (PDX) model established from a patient resistant to ARSI and chemotherapy. Through genome-wide analysis using chromatin immunoprecipitation followed by sequencing, the investigators identified distinct OCT1 binding sites in PDX 201.1 A compared to treatment-naïve cells. Bioinformatic analyses linked OCT1-regulated genes to cell migration and immune regulation processes. Particularly, the study group observed that C-terminal Binding Protein 2 (CTBP2), a target of OCT1 and AR, correlated with poor prognosis and exerted immunosuppressive effects within the tumor microenvironment. Metascape analysis indicated that CTBP2 knockdown influenced genes involved in the immune response to bacteria. Additionally, TISIDB analysis revealed a relationship between CTBP2 expression and immune cell infiltration in prostate cancer, suggesting its potential role in immune evasion in CRPC.
In conclusion, the study unveils the intricate network involving OCT1 and AR in AR-positive CRPC and underscores the significance of CTBP2 in immune modulation and tumor progression. Targeting CTBP2 emerges as a promising therapeutic strategy for aggressive AR-positive CRPC. Future research should focus on validating these findings to pave the way for novel therapeutic approaches in the management of CRPC.
Source: bmccancer.biomedcentral.com/articles/10.1186/s12885-024-12298-3
