The Molecular Biology of Soft-Tissue Sarcomas and Current Trends in Therapy

Figure 2

Several ligands (IGF1/2, SCF, HGF, VEGF, and FGF) activate cell membrane receptor tyrosine kinases (IGF1R, C-KIT, C-MET, VEGFR-A, and FGFR) triggering shared interacting signal transduction pathways (PI3K/AKT, RAF/MAPK, and MTOR). The availability of ligands via paracrine secretion (IGF1), autocrine loops (VEGF), or ligand binding (IGFBPs) can modulate activation of these pathways. Molecular anomalies of the receptors or the downstream signals lead to constitutive activation or dysregulation of these signals. Multiple cell processes including proliferation, differentiation, angiogenesis, and survival are promoted as a result of the activation of these main pathways in sarcomas and other neoplasms. Actionable targets are listed that may interfere with the abnormal signalling and could result in beneficial biologic and clinical effects.