Table 2. New drugs under investigation for the treatment of CRPC.
| Target | Biological effect | Drug | Stage of clinical development |
|---|---|---|---|
| 17α hydroxylase/C17, 20 lyase | Suppression of adrenal androgen precursors | Abiraterone acetate | Phase I/II |
| HSP90 | Inhibition of AR signalling | 17-AAG | Phase II |
| 17-DMAG | Phase I | ||
| HDAC | Downregulation of AR | SAHA | Phase II |
| FK228 | Phase II | ||
| Vitamin D receptor | Agonism of VDR antiproliferative effects | DN-101 | Phase III |
| EB1089 | Phase I | ||
| PI3 kinase | Inhibit PI3K signalling axis | P1-103 ZSTK474 | Phase I trials anticipated to start in 2006 |
| mTOR | Inhibition of mTOR-dependent protein translation | CCI-779 | Phase II |
| RAD001 | Phase II | ||
| IGF1-R | Inhibit IGF1-R signalling axis | CP-751, 851 | Phase I |
| Phase II trials anticipated to start 2006 | |||
| ErbB receptor family | Inhibit erbB signalling axis | Gefitinib | Negative phase II trials |
| Pertuzumab (2C4) | Negative phase II trials | ||
| Survivin | Proapoptotic | YM-155 | Phase II |
| BCl-2 | Proapoptotic | G3139 | Phase II |
| VEGF | Antiangiogenesis | Bevacizumab | Phase III |
| VEGFR | Antiangiogenesis | BAY 43-9006 | Phase II |
| AZD2171 | Phase I/II | ||
| ETA | Inhibition of endothelin-1 axis | Atrasentan | Phase III trials (first trial did not meet its end point) |
| β-Tubulin | Cell-cycle arrest | Ixabepilone | Phase II/Phase III |
| E7389 |
HSP, heat shock protein; AR, androgen receptor; 17-AAG, 17- allylamino-17-demethoxygeldanamycin; 17-DMAG, 17-dimethylaminoethylamino-17-demethoxygeldanamycin; HDAC, histone deacetylase; SAHA, suberoylanilide hydroxyamic acid; PI3K, phosphatidylinositol-3-kinase; mTOR, mammalian target of rapamycin; IGF1-R, insulin growth factor receptor; VEGF (R), vascular endothelial growth factor (receptor); ETA, endothelin-A.