Fig. 7 | Signal Transduction and Targeted Therapy

Fig. 7

From: Multipronged SMAD pathway targeting by lipophilic poly(β-amino ester) miR-590-3p nanomiRs inhibits mesenchymal glioblastoma growth and prolongs survival

Fig. 7

Proposed mechanistic model. GBM cells with high levels of TGFBR2 display enhanced SMAD2/3 signaling. These cells exhibit an accessible chromatin state at the TGFBR2 promoters associated with direct binding of architectural transcription factor HMGA1 and stem cell drivers Oct4 and Sox2. This increase in TGFBR2 levels associates with SMAD2/3 signaling activation, reduced sensitivity to TMZ and increases self-renewal capacity in GBM neurospheres. LiPBAE nanoparticles efficiently deliver miR-590-3p to simultaneously block multiple SMAD2/3 targets, induce tumor regression and prolong animal survival. These findings highlight the therapeutic potential of blocking TGFBR2 signaling in rGBM. Created in BioRender. Lopez-Bertoni, H. (2025) https://BioRender.com/u19d660

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