Targeting TGFβ/SMAD Pathway

    • Targeting TGFβ can be done by different drugs that include antisense oligonucleotides (AONs), neutralizing antibodies that inhibit ligand–receptor interactions, receptor domain-immunoglobulin fusions that sequester ligands and prevent binding to receptors, and receptor kinase inhibitors.
      • AONs (target TGFβ2): trabedersen (AP12009) and antisense gene-modified allogenic tumor vaccine: Belagenpumatucel-L (Lucanix) are currently in clinical trials.
      • Antibodies: Fresolimumab (GC-1008)—binds TGFβ1 and TGFβ2; IMC-TR1—targets TβRII
      • TGFβ kinase inhibitors/small-molecule inhibitors: LY2157299 (galunisertib); TEW-7197
    • Although TGFβ targeting agents, such as galunisertib, have shown dramatic therapeutic effects in animal cancer models and in some cancer patients, it is still ents is achieved and currently there is no predictive biomarker for response to drugs targeting the TGFβ pathway.
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