Review Article

Factors Implicated in Radiation Therapy Failure and Radiosensitization of Prostate Cancer

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/targetPathwayPrediction of RT failurePotential therapeutic inventions/agents

D2-40Metastatic‡ (7–11)Pelvic radiation
OLN+Metastatic‡ (12)Pelvic radiation
ARHypersensitive‡ (28)AR silencing, MDV3100 [53]
Statins [54, 55], abiraterone [56]
PKAHypersensitive‡ (4), (32)AR silencing, PKA knockdown [31]
Ki-67/MDM2Proliferation‡ (48)AR silencing, antisense-MDM2 [49]
p16Proliferation‡ (4)AR silencing
erb1/EGFR (HER-1)OutlawNYDGefitinib [15, 57]
Erlotinib [58]
PI3K/AKT/mTOR inhibitors [59]
HSP-90 inhibitors [60]
erb2/HER2 (HER-2/neu)OutlawNYDPertuzumab
PI3K/AKT/mTOR inhibitors [59]
HSP-90 inhibitors [60]
VEGF-ROutlawNYDBevacizumab, aflibercept, sunitinib [23]
PI3K/AKT/mTOROutlawNYDPI3K/AKT/mTOR inhibitors [59]
HSP-90 inhibitors [60]
NF-κB/Stat3Bypass± (4)Curcumin [34]
Bcl-2Bypass± (4)Docetaxel [61] AT-101 [23]
ClusterinBypass±OGX-001 [16]
COX-2Bypass‡ (47)Celecoxib, etoricoxib [6264]
CGA (somatostatin receptor)BypassNYDLanreotide [6567]
CD44/CD133Stem cellNYDPI3K/mTOR inhibitor NVP-BEZ235 [68]
CD44/CD133Stem cellNYDGamma-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.