Tumor hypoxia, DNA repair and prostate cancer progression: new targets and new therapies.
Increasingly, the tumor microenvironment and hypoxia are being studied as potential prognostic factors in prostate cancer given their effects on the hypoxia inducible factor-1alpha and vascular endothelial growth factor signaling pathways. Based on immunohistochemical studies using hypoxic cell markers and direct oxygen-electrode measurements, clinically relevant levels of hypoxia are detected in 30-90% of prostate cancers. Exciting new data suggest that hypoxia can alter cell-cycle checkpoints and DNA repair within the prostate epithelium, thereby driving genetic instability and tumor aggression. Novel therapies designed to target the hypoxic response and resulting defective DNA repair may therefore be effective as chemoprevention agents or as adjuncts to surgery, radiotherapy and chemotherapy to improve clinical outcome.
Chan
Norman
N
Departments of Medical Biophysics & Radiation Oncology, University of Toronto, Princess Margaret Hospital (University Health Network), Toronto, Ontario, Canada. nchan@uhnres.utoronto.ca
Milosevic
Michael
M
Bristow
Robert G
RG
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D004260:DNA Repair / Q000502:physiology*; D018450:Disease Progression; D015195:Drug Design; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000503:physiopathology*
D000970:Antineoplastic Agents; D051795:Hypoxia-Inducible Factor 1, alpha Subunit