Targeting MYC driven PC by combining targeted radionuclide therapy with ribosome biogenesis inhibition as a new therapy in CRPC and neuroendocrine PC

Metastatic castration-resistant prostate cancer (mCRPC) is commonly characterised by overexpression of the MYC oncogene, including the ~25% with neuroendocrine-differentiation (NEPC) that overexpress N-MYC. With my collaborators, we have identified and developed a new paradigm for targeting MYC via the inhibition of the key MYC target, RNA Polymerase I and its transcripts, the ribosomal RNA. Moreover our data demonstrate that RNA Pol I transcription inhibitors sensitise the ribosomal RNA genes to treatments that activate DNA damage. In this project we will explore synergies between radionuclide-targeted therapy (RT) and inhibition of RNA Pol I transcription using preclinical models including patient derived xenografts of CRPC and NEPC.