Emerging roles of radioresistance in prostate cancer metastasis and radiation therapy.
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.
Cancer Care Centre and Prostate Cancer Institute, St. George Hospital, Gray St Kogarah, Sydney, NSW, 2217, Australia.
Lei
L
Chang
Peter H
PH
Graham
Jingli
J
Hao
Joseph
J
Bucci
Paul J
PJ
Cozzi
John H
JH
Kearsley
Yong
Y
Li
D000818:Animals; D001343:Autophagy; D003131:Combined Modality Therapy; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D008297:Male; D009362:Neoplasm Metastasis; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000528:radiation effects; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000532:radiotherapy* / Q000628:therapy; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011836:Radiation Tolerance; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology / Q000627:therapeutic use; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D011838:Radiation-Sensitizing Agents; D058570:TOR Serine-Threonine Kinases