Genetic interactions in translational research on cancer

Figure 1 Diagram of genetic interactions. A: The essential biological function E is regulated by pathways A and B. A functional change in either of these pathways, such as a mutation in A1 or B1, is insufficient to induce dysfunction of E. However, the simultaneous presence of a mutation in A1 and a mutation in any of B1, B2 or B3 induces dysfunction of E (or phenotype changes). Thus, A1 has genetic interaction with B1, B2 and B3, and vice versa; B: The essential biological function E is regulated by pathway A alone, in which A2 is a multiprotein complex composed of X, Y and Z, while A3 has homologues of α, β and γ. Genetic interaction may exist among X, Y and Z, and among A3α, β and γ.

Figure 2 Growth factor activated pathways and their crosstalks. Growth factors, such as epidermal growth factor (EGF), vascular endothelial grow factor (VEGF), fibroblast growth factor (FGF), hepatocyte growth factor (HGF), insulin-like growth factor (IGF) and platelet derived growth factors (PDGF), interact with their receptors and activate the common downstream pathways, such as PI3K/AKT, RAS/RAF/MAPK and SRC/JAK/STAT pathways. Moreover, there are crosstalks among those pathways in regulating transcription factors and apoptotic/survival proteins. Inhibiting a single target or blocking a single pathway is often not sufficient to induce apoptosis in cancer cells.