New York: Researchers have discovered that the protein BRD4 could be an important new target to prevent castration-resistant prostate cancer metastases.
Bromodomain-containing protein 4 is a protein in humans encoded by the BRD4 gene. Castration-resistant prostate cancer is a highly aggressive form of prostate cancer that often leads to the development of lethal metastases that kills more than 31,000 American men every year.
The standard of care treatment for these patients typically includes disruption of androgen receptor signalling with drugs called ‘androgen deprivation therapy’.
“While effective for an average of two-three years, this therapy eventually fails to impede cancer progression, due to acquired resistance to the drugs,” study authors from Boston University in the US said.
Researchers have long studied a family of three closely-related proteins, called BET bromodomain proteins, composed of BRD2, BRD3 and BRD4, which regulate gene expression.
The researchers examined prostate cancer cell lines that model common forms of prostate cancer that are resistant to androgen deprivation therapy. They found that BRD4, but not similar family members BRD2 or BRD3, regulates the expression of key proteins that directly contribute to prostate cancer disease progression.
“These findings are novel because, until now, it was not clear which of the BET family of proteins regulate transcriptional programmes, or how they influence prostate cancer cell morphology (shape and polarity), motility (the ability to move independently) and invasiveness, each of which is associated with the ability to metastasize.
According to the researchers, this study is significant because current therapeutic options for castration-resistant prostate cancer are limited and focus primarily on suppressing prostate tumour cells that rely on androgen receptor signalling.
“As prostate tumour cells become resistant to therapy, their reliance on androgen receptor signalling is reduced and alternative signalling mechanisms are activated. Out of this complex mixture, the metastatic cells arise,” the study authors wrote.
The researchers believe it is imperative to identify new targets that regulate the expression of critical transcription factors across diverse prostate cancer cell types in order to block migration and invasion and eventual metastasis.
