Prostate-specific antigen and probasin promoters (PSA/PB promoters)

The prostate-specific antigen (PSA) and probasin (PB) promoters are DNA regulatory sequences used to drive gene expression specifically within prostate tissue. PSA (Kallikrein-3) is a serine protease primarily produced by the prostate, and its promoter contains androgen response elements (AREs) that make it highly sensitive to androgen receptor (AR) activation [1][3]. The probasin promoter, often utilized in an engineered form known as ARR2PB, is derived from the rat probasin gene and is one of the most specific promoters for targeting prostate epithelial cells [2][4]. In the context of oncology, these promoters are not therapeutic targets themselves but are critical tools for 'transcriptional targeting' in gene therapy and oncolytic viruses, such as CG7870 and CV706 [5]. By placing therapeutic payloads or viral replication genes under the control of these promoters, researchers aim to restrict drug activity to PSA-positive prostate cancer cells while minimizing systemic toxicity. However, a significant challenge remains in advanced prostate cancer, where the downregulation of AR or changes in co-regulator profiles can lead to reduced promoter activity and therapeutic escape [6].

Other names

KLK3 promoterARR2PB promoterProstate-specific regulatory elementsPSA-responsive promoterProbasin-derived promoter

These promoters are utilized as tissue-specific transcriptional regulators in gene therapy and oncolytic virotherapy to drive the expression of therapeutic genes or viral replication specifically within prostate epithelial and cancer cells by responding to endogenous androgen receptor signaling.