Mintegia: “Therapeutic rationale for targeting dual-SMAD inhibiting proteins in breast cancer”

Hizlariak / Ponentes: Maider Zabala (CEO) & Neethan Amit Lobo (CEO) – ONENA Medicines.
Data / Fecha: 2019ko ekainak 28 / 28 de junio de 2019.
Ordua / Hora:  13:30-14:00.
Lekua / Lugar: Biodonostia OIIko Prestakuntza Aretoan, 3.Solairua. / IIS Biodonostia, Sala de Formación, Planta 0.

Laburpena / Resumen:
Transforming growth factor-β (TGF-β) signaling plays a key role in tissue homeostasis, which is accomplished through dynamic regulation of many cellular processes, including cell growth and differentiation. The secreted TGF-β family ligands bind to homo/heterodimeric cell surface receptors, which triggers the phosphorylation of receptor regulated-SMAD signaling molecules and their translocation to the nucleus to initiate target gene expression. Secreted TGF-β ligands can be divided into two classes: TGF-β -like ligands that signal through R-SMAD 2/3 and BMPs that signal through R-SMAD 1/5/8. Recent evidence demonstrated that simultaneous synthetic suppression of these two classes of ligands results in in vitro expansion of basal cell populations from epithelial tissues from all three germ layers. We discovered that a TGF-β -like ligand naturally performs a dual-SMAD inhibiting function to promote the self-renewal of mammary stem cells. In addition, this ligand is produced by tumorigenic drug resistant breast cancer cells to promote their immortality. Furthermore, we found a novel interaction between this TGF-β -like ligand with a receptor that is specific to drug resistant cancer cells. Genetic abrogation of the TGF-β -like ligand in different PDX models showed that this protein is necessary for tumor growth. As TGF-β inhibitors have shown considerable clinical promise, attenuating dual-SMAD inhibition represents a unique opportunity to create novel targeted therapies for the treatment of advanced breast cancer. Onena Medicines is the first and the only company in the world that is targeting dual-SMAD inhibition.