A specific tRNA may reverse treatment resistance in prostate cancer

A study published in Nature has identified an unexpected mechanism controlling lineage plasticity and resistance to androgen receptor (AR)-targeted therapies in prostate cancer.
Researchers discovered that reduced expression of a specific transfer RNA, tRNAArg(UCU)-1, contributes to the loss of androgen dependence and the development of aggressive, treatment-resistant cellular states. The mechanism involves altered production of chromatin-remodelling proteins, including SMARCC2, which help maintain prostate cancer cells in an AR-dependent state. Restoring tRNAArg(UCU)-1 or SMARCC2 in experimental models recovered AR signalling and increased sensitivity to androgen-targeted treatment.

Analyses of patient tumours also linked reduced tRNAArg(UCU)-1 expression with neuroendocrine differentiation, earlier metastasis and poorer survival. The findings suggest that some forms of acquired resistance may be biologically reversible rather than permanently fixed, opening a potential route towards RNA-directed therapies designed to restore treatment sensitivity.

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