 Targeting the BMI1 oncogene mRNA using small molecules
 Biography Overview Many cancers relapse after standard therapy, and a subset of cancer cells with self-renewal features called ‘cancer stem-like cells’ (CSCs) were identified to be resistant to standard chemo- and radiotherapy. BMI1 (for ‘B cell-specific Moloney murine leukemia virus integration site 1’) is a validated CSC target, whose overexpression in CSCs from various cancers is correlated with therapeutic failure. CSCs are addicted to high BMI1 levels and BMI1 depletion leads to tumor regression. BMI1 is a cellular protein member of the polycomb repressor complex 1 (PRC1) that represses the transcription of multiple tumor suppressors through PRC1-mediated epigenetic silencing. Since BMI1 lacks enzymatic activity, BMI1 was considered an undruggable oncogene and there are currently no BMI1 inhibitors in the clinic. We propose here a novel mechanistic approach to evaluate small molecule targeting of the BMI1 RNA. This work will also help to promote the emerging therapeutic approaches to target oncogenic messenger RNAs against cancer.
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