Targeting MYC-driven translation
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Overactivity of the transcription factor MYC plays a central part in the progression of multiple myeloma through upregulation of ribosome synthesis and translation activity. Using a
high-throughput screening approach, Manier et al. have identified a series of synthetic analogues of the rocaglate natural product class, which potently inhibited proliferation of multiple
myeloma cell lines that overexpress MYC. CMLD010509, the most potent rocaglate, selectively downregulated the oncogenic MYC-driven translation programme in multiple myeloma cells. In mouse
models of multiple myeloma, twice-weekly injection of CMLD010509 for 4 weeks reduced tumour burden and prolonged survival.
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