PMR-116, a novel inhibitor of ribosome biogenesis with antitumor activity in preclinical models of prostate cancer

Abstract

Abstract Advanced prostate cancer is characterised by mutations and amplifications of genes involved in regulating protein synthesis. PTEN-loss stimulates activity of the mTOR pathway, while amplification of MYC leads to increased ribosome biogenesis and elevated mRNA translation rate. Our previous work has demonstrated the efficacy of co-targeting ribosome biogenesis, via inhibition of RNA Pol I activity, and 4E-BP1 phosphorylation to suppress prostate cancer growth in vivo in GEMM of PCa and in patient-derived xenografts (Rebello et al., Clinical Cancer Research, 2016; Lawrence et al., European Urology, 2018). In a collaboration with Pimera Inc., we investigat..