Dissecting the function of RAI2 in anti-androgen resistance in prostate cancer

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The RAI2 gene, which was initially identified at ITB in Hamburg as a novel tumor suppressor, holds potential as novel drug-able target and actionable marker of anti-androgen therapy. Molecular characterization of the RAI2 protein in luminal breast cell lines already revealed that it is acting as a transcriptional co-regulator involved in hormonal responses as well as in the response to genotoxic stress in breast cancer cells. Also other researcher have previously reported that integration of viral mouse mammary tumor virus (MMTV) into the RAI2 gene locus is associated with the emergence of recurrent and hormone-independent breast tumors, emphasizing a particular role for RAI2 depletion in the progression from hormone-dependent to hormone-independent tumors. Although RAI2 protein function in prostate cancer cells remains completely uncharacterized by now, first results show that it is likely to resemble a specific function also in hormone dependent prostate tumors. We hypothesize that loss of RAI2 function in androgen-dependent prostate tumors contributes to progress to hormone independence and metastasis formation. The key objective of this research project is therefore to analyse RAI2 protein function in hormone dependent prostate cancer cells and to dissect its potential role in anti-androgen resistance. In addition, we intend to determine RAI2 expression in prostate cancer samples and to evaluate the potential of RAI2 expression to serve as novel biomarker for prostate cancer therapies and to validate on large PCa patient cohorts the practicality of RAI2, AR-V7 and PSMA detection as blood-based biomarkers.