Table 1: Selection of potential markers/targets and pathways implicated in the development of radioresistant prostate cancer, their significance in predicting radiation therapy (RT) failure, and potential therapeutic inventions/agents.

Marker/target Pathway Prediction of RT failure Potential therapeutic inventions/agents D2-40 Metastatic ‡ (7–11) Pelvic radiation OLN+ Metastatic ‡ (12) Pelvic radiation AR Hypersensitive ‡ (28) AR silencing, MDV3100 [53] Statins [54, 55], abiraterone [56] PKA Hypersensitive ‡ (4), (32) AR silencing, PKA knockdown [31] Ki-67/MDM2 Proliferation ‡ (48) AR silencing, antisense-MDM2 [49] p16 Proliferation ‡ (4) AR silencing erb1/EGFR (HER-1) Outlaw NYD Gefitinib [15, 57] Erlotinib [58] PI3K/AKT/mTOR inhibitors [59] HSP-90 inhibitors [60] erb2/HER2 (HER-2/neu) Outlaw NYD Pertuzumab PI3K/AKT/mTOR inhibitors [59] HSP-90 inhibitors [60] VEGF-R Outlaw NYD Bevacizumab, aflibercept, sunitinib [23] PI3K/AKT/mTOR Outlaw NYD PI3K/AKT/mTOR inhibitors [59] HSP-90 inhibitors [60] NF-κB/Stat3 Bypass ± (4) Curcumin [34] Bcl-2 Bypass ± (4) Docetaxel [61] AT-101 [23] Clusterin Bypass ± OGX-001 [16] COX-2 Bypass ‡ (47) Celecoxib, etoricoxib [62–64] CGA (somatostatin receptor) Bypass NYD Lanreotide [65–67] CD44/CD133 Stem cell NYD PI3K/mTOR inhibitor NVP-BEZ235 [68] CD44/CD133 Stem cell NYD Gamma-tocotrienols [69]

OLN+: occult lymph node metastasis; AR: androgen receptor; PKA: protein kinase A; EGFR: epithelial growth factor receptor; VEGF-R: vascular endothelial growth factor receptor; PI3K/AKT/mTOR: phosphatidylinositol 3 kinase (PI3K)/AKT/mammalian target of rapamycin; NF-κB/Stat3: transcription factors nuclear factor-kappa B (NF-κB) and signal transducers and activators of transcription 3 (Stat3), COX-2: cyclooxygenase 2; CGA: chromogranin A; ‡: significant prediction of RT failure has been reported. ±: significant prediction of RT failure has not been reported. NYD: not yet determined.