Table 1.
Candidate compounds (A) and biomarkers (B) discussed at the Ewing sarcoma summit.
| Compound | Target/activity | Evidence |
|---|---|---|
| A. | ||
| Midostaurin (PKC412) | Broad spectrum protein kinase inhibitor | EWS-FLI1 signature based |
| Mithramycin | Antibiotic | EWS-FLI1 signature based |
| YK-4-279 | EWS-FLI1 interacting small molecule | Inhibition of EWS-FLI1 protein interaction/activity |
| ESAP1 | EWS-FLI1 interacting peptide | Inhibition of EWS-FLI1 protein interaction/activity |
| Enzastaurin | PKC inhibition | EWS-FLI1 repressive signature |
| Tranylcypromine | LSD1 inhibition | EWS-FLI1 repressive signature |
| Ubiquitin ligase inhibitors | CDT2 inhibition | Not discussed |
| Olaparib, iniparib, veliparib | PARP1 inhibition | Frequently gained and overexpressed |
| MLN4294 | NEDD8 inhibitor | Not discussed |
| Bisphosphonates (zoledronic acid) | Inhibitor of osteoclastogenesis | Mouse xenografts |
| BHQ880 | DKK1 inhibitor | Osteoblastogenesis induction |
| IFN-γ | Type II interferon | Sensitization to TRAIL, inhibition of tumor cell invasion, and migration |
| Peptide primed dendritic cells | Generation of ES specific, allo-restricted T-cells | In vitro and in vivo ES cell lysis |
| GD2 specific chimeric antigen receptors (CARs) | Generation of antigen specific T-cells | In vitro and in vivo ES cell lysis |
| IGF1R antibody coupled liposomal doxorubicin | Anti IGF1R activity combined with cytotoxic drug targeting to ES cells | Under development |
| MST1R (RON), HCK, FES, EPHB2, LMTK2, PDGFRB | Kinases | IGF1R sensitizer RNAi screen |
| OSI-906 | Dual IGF1R/IRA inhibitor | In vitro growth inhibition |
| Metformin | Reduces circulating insulin | In vitro growth inhibition |
| CD99 antibody O662 | Cell death and autophagy induction | In vitro growth inhibition |
| Nutlin 3 | P53 activation | In vitro growth inhibition |
| Biomarker | Function | Evidence |
| B. | ||
| Telomere length | Replicative potential | Telomeric repeat PCR |
| Copy number changes at chromosomes 1q, 8q, 16, and 20 | Unknown | Array CGH, MLPA |
| Metadherin (MTDH) | Metastasis, chemoresistance | Chromosome 8 encoded, frequent gain |
| CDT2 | Protein ubiquitinylation | Chromosome 1q encoded, frequent gain |
| Circulating tumor DNA | Marker of tumor load | qPCR detection in plasma samples |
| Circulating miRNAs | Marker of tumor load | Stem-loop qPCR detection in plasma or whole blood |
| ErbB4 | Metastasis | PuMa assay in mouse |
| STEAP1 | Good prognostic marker | Retrospective correlative study in patients |
| LGR5 | Stem cell marker | Expression study in patient materials |
| GPR64 | G-protein coupled receptor | Promotion of lung metastasis |
| EPHB2 | Metastasis associated kinase | Comparison of localized and metastatic tumor samples |
| IRA | IGRF1R inhibitor resistance | Correlative expression study |