Cancer and Metastasis Reviews

, Volume 33, Issue 2–3, pp 469–496 | Cite as

Emerging roles of radioresistance in prostate cancer metastasis and radiation therapy

  • Lei Chang
  • Peter H. Graham
  • Jingli Hao
  • Joseph Bucci
  • Paul J. Cozzi
  • John H. Kearsley
  • Yong Li


Radiation therapy (RT) continues to be one of the most popular treatment options for localized prostate cancer (CaP). Local CaP recurrence after RT is a pattern of treatment failure attributable to radioresistance of cancer cells. One major obstacle to RT is that there is a limit to the amount of radiation that can be safely delivered to the target organ. Recent results indicate that phosphoinositide 3-kinase (PI3K)/Akt/phosphatase and tensin homolog (PTEN)/mammalian target of rapamycin (mTOR) signaling pathway, autophagy, epithelial–mesenchymal transition (EMT) and cancer stem cells (CSCs) are involved in CaP metastasis and radioresistance. Emerging evidence also suggests that combining a radiosensitizer with RT increases the efficacy of CaP treatment. Understanding the mechanisms of radioresistance will help to overcome recurrence after RT in CaP patients and prevent metastasis. In this review, we discuss the novel findings of PI3K/Akt/PTEN/mTOR signaling pathway, autophagy, EMT and CSCs in the regulation of CaP metastasis and radioresistance, and focus on combination of radiosensitizers with RT in the treatment of CaP in preclinical studies to explore novel approaches for future clinical trials.


Prostate cancer Radiation therapy Radioresistance Radiosensitizer PI3K/Akt/mTOR Autophagy EMT Cancer stem cell 



Androgen deprivation


Adenoviral-mediated E2F1


Aldehyde dehydrogenase


Androgen receptor




Antisense Bcl-2 oligodeoxynucleotide


Ataxia telangiectasia mutated


Arsenic trioxide


Biochemical recurrence


Breast cancer resistance protein


Breast cancer stem cells


Basic helix-loop-helix




Prostate cancer


CD44 variants






Castration-resistant prostate cancer


Cancer stem cells


Circulating tumor cells




Dehydroxymethyl derivative of epoxyquinomicin


DX; 3,4-dihydroxybenzohydroxamic acid


Double-strand breaks


External beam radiotherapy


Epidermal growth factor receptor


Epithelial–mesenchymal transition


Epithelial cell adhesion molecule


Endoplasmic reticulum


Fluorescence-activated cell sorting


Fibroblast growth factor receptor 2IIIb


Fms-like tyrosine kinase-3


Gamma knife surgery


Hepatocellular carcinoma


Histone deacetylase inhibitors




Hydroxyl-3-methylglutaryl coenzyme A


Head and neck squamous cell carcinoma


Insulin-like growth factor-type 1 receptor


Image-guided radiation therapy


Intensity modulated radiation therapy


Ionizing radiation


Monoclonal antibody


Magnetic activated cell sorting


Mitogen-activated protein kinase


Mesenchymal to epithelial transition






Multidrug resistance protein 1


Mammalian target of rapamycin


Nuclear factor-κB


Non-obese diabetic/severe combined immunodeficiency


Nitric oxide donating nonsteroidal anti-inflammatory drugs


NAD(P)H:quinone oxidoreductase 1


Nonsteroidal anti-inflammatory drugs


Palomid 529




Prostatic acid phosphatise


Polymerase chain reaction


Platelet-derived growth factor


Pyruvate dehydrogenase kinase


Phosphoinositide 3-kinase


Protein kinase B


Prostate-specific antigen


Phosphatidylinositol 3,4-bisphosphate


Phosphatidylinositol 3,4,5-trisphosphate


Phosphatidylinositol 4-phosphate


Phosphatidylinositol 4,5-bisphosphate


Phosphatase and tensin homolog


Radical prostatectomy




Radiation therapy


Suberoylanilide hydroxamic acid




Small interfering RNA


Sublethal radiation damage


Sodium selenite


Transforming growth factor-β


Tyrosine kinase inhibitors


Tuberous sclerosis complex 2


Valproic acid


Vascular endothelial growth factor receptor



Our prostate cancer radiation research project was supported in part by a NH&MRC Career Development Fellowship; Cancer Research Trust Fund at Cancer Care Centre, St George Hospital; and Prostate and Breast Cancer Foundation. The authors thank the technical support from Mr Ken Hopper, Mr Ese Enari, Mr Alex Wallace, and Mr Peter Treacy from the Cancer Care Centre, Sydney, Australia.


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Lei Chang
    • 1
    • 2
  • Peter H. Graham
    • 1
    • 2
  • Jingli Hao
    • 1
    • 2
  • Joseph Bucci
    • 1
    • 2
  • Paul J. Cozzi
    • 2
    • 3
  • John H. Kearsley
    • 1
    • 2
  • Yong Li
    • 1
    • 2
  1. 1.Cancer Care Centre and Prostate Cancer InstituteSt. George HospitalSydneyAustralia
  2. 2.St George and Sutherland Clinical School, Faculty of MedicineUniversity of New South WalesKensingtonAustralia
  3. 3.Department of SurgerySt. George HospitalSydneyAustralia

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