Table 1.
Selected approved and investigational targeted agents in sarcoma
| Agent | Status | Specificity |
|---|---|---|
| Tyrosine Kinase Inhibitors | ||
| Imatinib mesylate | FDA approved for GIST, DFSP | kit, abl, PDGFR |
| Sunitinib | FDA approved GIST (2nd line) | Multiple tyrosine kinases: PDGFR, kit, RET, CSF-1R, Flt3, VEGFR |
| Sorafenib | Phase II125, 141 | Multiple kinases: kit, VEGFR, PDGFR, raf |
| Gefitinib | Phase II107 | EGFR |
| R1507 | Phase I/II142 | IGF-1R |
| Figitumumab | Phase I143 | IGF-1R |
| Crizotinib | Phase I26 | Alk/ Met |
| ARQ197 | Phase II113 | Met |
| mTORC1 Inhibitors | ||
| Sirolimus | Phase II144 | mTORC1 |
| Temsirolimus | Phase II145 | mTORC1 |
| Ridaforolomus (deferolimus) | Phase II/III116 | mTORC1 |
| Everolimus | Phase I/II143 | mTORC1 |
| mTORC catalytic domain inhibitors | ||
| AZD8055 | Preclinical/Phase I146 | mTORC1/mTORC2 |
| PI3K Inhibitors | ||
| GSK1059615 | Phase I147 | PI3K |
| Dual mTOR/PI3K Inhibitors | ||
| BEZ235 | Phase I148 | PI3K class I, mTOR |
| AKT Inhibitors | ||
| MK2206 | Phase I149 | Akt |
| Ras Pathway Inhibitors | ||
| Selumetinib | Phase II150 | Mek |
| Anti-Angiogenic Agents | ||
| Bevacizumab | Phase II130, 151 | VEGFR |
| Pazopanib | Phase II152 | VEGFR, PDGFR, kit, |
| Cediranib | Phase I153 | VEGFR |
| Brivanib | Phase II154 | VEGFR, FGFR |
| ABT-510 | Phase II131 | Thrombospondin mimetic |
| Pro-Apoptotic Agents | ||
| RG7112 (RO5045337) | Phase I/II155 | Hdm2-p53 interactions |
| Dulamnermin (r-hu anti-Apo2/TRAIL) | Phase I96 | TRAIL-R |
| Oblimersen (G3139) | Phase I156 | Bcl-2 (antisense oligonucleotide) |
| Cell Cycle Progression/Proliferation Inhibitors | ||
| PD0332991 | Phase I/II157 | Cdk4 |
| Ispinesib | Phase I87, 88 | Kinesin |
| MLN8054, MLN8237 | Preclinical/Phase I126 | AurkA |
| Epigenetic Modifier Inhibitors | ||
| Panobinostat | Phase II158 | HDAC |
| Vorinostat | Phase II159 | HDAC |
| Azacytidine | Phase I/II160 | DNA methyltransferase |