Targeting SMAD-Dependent Signaling: Considerations in Epithelial and Mesenchymal Solid Tumors

• Main Authors: Farhana Runa (Author), Gabriela Ortiz-Soto (Author), Natan Roberto de Barros (Author), Jonathan A. Kelber (Author)
• Format: Book
• Published: MDPI AG, 2024-03-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.3390/ph17030326; 1424-8247
• Keywords: Transforming Growth Factor-β (TGF-β); SMADs; Epithelial-Mesenchymal Transition (EMT); Inhibitory SMADs (I-SMADs); non-canonical SMAD signals; nucleocytoplasmic trafficking; Medicine; R; Pharmacy and materia medica; RS1-441
• Source: Pharmaceuticals, Vol 17, Iss 3, p 326 (2024)

SMADs are the canonical intracellular effector proteins of the TGF-β (transforming growth factor-β). SMADs translocate from plasma membrane receptors to the nucleus regulated by many SMAD-interacting proteins through phosphorylation and other post-translational modifications that govern their nucleocytoplasmic shuttling and subsequent transcriptional activity. The signaling pathway of TGF-β/SMAD exhibits both tumor-suppressing and tumor-promoting phenotypes in epithelial-derived solid tumors. Collectively, the pleiotropic nature of TGF-β/SMAD signaling presents significant challenges for the development of effective cancer therapies. Here, we review preclinical studies that evaluate the efficacy of inhibitors targeting major SMAD-regulating and/or -interacting proteins, particularly enzymes that may play important roles in epithelial or mesenchymal compartments within solid tumors.