Table 3 Functional information for drugs and drug targets identified by bioinformatic screening of genes that are consistently upregulated or downregulated in soft tissue sarcomas, across three species. Screening of sets of 53 genes that are upregulated in sarcoma and 38 genes that are downregulated was performed using the Enrichr web tool (see Methods and Fig. 6)
gene set | drug or target | comment | reference |
|---|---|---|---|
up in sarcoma | piperlongumine-1764 | natural product with anti-cancer properties | [44] |
up in sarcoma | TGFA (transforming growth factor É‘) | targeted for immunotoxin therapy | [45] |
up in sarcoma | FGF7 (fibroblast growth factor 7) | proposed therapeutic target | [46] |
up in sarcoma | saracatinib (AZD-0530) | investigational anti-cancer drug; dual-kinase inhibitor (Src and Bcr-Abl) | [47] |
up in sarcoma | MK-2206 | investigational anti-cancer drug; selective protein kinase B (Akt) inhibitor | [48] |
up in sarcoma | linsitinib (OSI-906) | investigational anti-cancer drug; inhibitor of insulin receptor and insulin-like growth factor 1 receptor | [49] |
up in sarcoma | GSK-1059615 | phosphatidylinositol 3-kinase inhibitor and mTOR inhibitor | [50] |
down in sarcoma | PDGFBB (platelet-derived growth factor BB monomer) | frequently drives sarcoma growth via autocrine signaling | [51] |
down in sarcoma | rosiglitazone | peroxisome proliferator-activated receptor-É£ agonist | [52] |
down in sarcoma | HGF (hepatocyte growth factor) | HGF-MET signaling axis implicated in soft tissue sarcoma proliferation | [53] |
down in sarcoma | AS601245 | c-Jun N-terminal kinase inhibitor; proposed as a co-therapeutic with rosiglitazone | [54] |
down in sarcoma | PD0325901 | mitogen-activated protein kinase kinase (MAPK/ERK kinase or MEK) inhibitor | [55] |
down in sarcoma | GSK-J4 | prodrug of GSK J1, a selective inhibitor of H3K27 histone demethylases JMJD3 and UTX | [56] |
down in sarcoma | AS605240 | phosphatidylinositol 3-kinase inhibitor | [57] |
down in sarcoma | selumetnib (AZD-6244, ARRY-142886) | ATP-independent inhibitor of mitogen-activated protein kinase kinase (MEK or MAPK/ERK kinase) 1 and 2; investigational cancer drug | [58] |