Targetable pathways for drug repurposing in gastric cancer

Figure 1 Mechanisms of action of repurposed drugs targeting the mitogen-activated protein kinase signaling pathway. Purple form indicated main pathway proteins; light blue form indicated drugs; dark blue form indicated proteins involved in the mechanism of action of the drug; “?” symbol indicated target is not clear. KLF: Krupple-like factor; DDIT4: DNA damage inducible transcript 4; MEK: Mitogen-activated protein; ERK: Extracellular signal-regulated kinase; MAPK: Mitogen-activated protein kinase.

Figure 2 Mechanisms of action of repurposed drugs targeting the phosphoinositide 3-kinase, p53, and hypoxia-inducible factor-1α signaling pathways. Purple form indicated main pathway proteins; light blue form indicated drugs; dark blue form indicated proteins involved in the mechanism of action of the drug; “?” symbol indicated target is not clear. ATRA: All-trans retinoic acid; Pin1: Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1; AMPK: Adenosine 5’-monophosphate-activated protein kinase; SRC: Proto-oncogene tyrosine-protein kinase Src; DRD2: Dopamine receptor D2; HDAC1/2: Histone deacetylase 1/2; PI3K: Phosphoinositide 3-kinase; AKT: Protein kinase B; mTOR: Mammalian target of rapamycin; SMHT2: Serine hydroxymethyl transferase 2.

Figure 3 Mechanisms of action of repurposed drugs targeting the Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway. Purple form indicated main pathway proteins; light blue form indicated drugs; dark blue form indicated proteins involved in the mechanism of action of the drug; IL11: Interleukin 11; JAK2: Janus kinase 2; STAT3: Signal transducer and activator of transcription 3.

Figure 4 Mechanisms of action of repurposed drugs targeting the Wnt, nuclear factor kappa B, and Hippo signaling pathways. Purple form indicated main pathway proteins; light blue form indicated drugs; dark blue form indicated proteins involved in the mechanism of action of the drug; “?” symbol indicated target is not clear. β-AR: Beta-adrenergic receptor; NF-κB: Nuclear factor kappa B; DKK1: Dickkopf-related protein 1; YAP: Yes-associated protein; TAZ: Transcriptional coactivator with PDZ-binding motif; HMGCR: Hydroxymethyl glutaryl-CoA.

Figure 5 Mechanisms of action of repurposed drugs with other target proteins/pathways. Purple form indicated main pathway proteins; light blue form indicated drugs; dark blue form indicated proteins involved in the mechanism of action of the drug; “?” symbol indicated target is not clear. ERK: Extracellular signal-regulated kinase; HIF-1α: Hypoxia-inducible factor-1α; NF-κB: Nuclear factor kappa B; TERT: Telomerase reverse transcriptase; TGF-β1: Transforming growth factor-β1; EGFR: Epidermal growth factor receptor; DR: Dopamine receptor.