Targeting castration-induced tumour hypoxia enhances the acute effects of castration therapy in a rat prostate cancer model.
What's known on the subject? and What does the study add? Castration therapy has rather modest effects on cell death in tumours but can be enhanced by other treatments targeting tumour stroma and vasculature. This study shows that the prostate becomes hypoxic following castration and that targeting hypoxic cells during castration therapy potently enhances the effects of castration.


OBJECTIVE
To explore the effects of castration therapy, the standard treatment for advanced prostate cancer, in relation to tumour hypoxia and to elicit its importance for the short- and long-term therapeutic response.


METHODS
We used the androgen-sensitive rat Dunning H prostate tumour model that transiently responds to castration treatment followed by a subsequent relapse, much like the scenario in human patients. Tumour tissues were analysed using stereological methods in intact, 1 and 7 days after castration therapy.


RESULTS
Hypoxia was transiently up-regulated after castration therapy and correlated with the induction of tumour cell apoptosis. When castration therapy was combined with tirapazamine (TPZ), a drug that targets hypoxic cells and the vasculature, the effects on tumour cell apoptosis and tumour volume were enhanced in comparison to either castration or TPZ alone.


CONCLUSIONS
The present study suggests that castration-induced tumour hypoxia is a novel target for therapy.
Johansson
Anna
A
Department of Medical Biosciences, Umeå University, Umeå, Sweden.
Rudolfsson
Stina Häggström
SH
Kilter
Sigrid
S
Bergh
Anders
A
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015687:Cell Hypoxia; D004195:Disease Models, Animal; D000860:Hypoxia / Q000503:physiopathology*; D007150:Immunohistochemistry; D008297:Male; D009919:Orchiectomy / Q000379:methods*; D009924:Organ Culture Techniques; D010101:Oxygen Consumption / Q000502:physiology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*; D011897:Random Allocation; D051381:Rats; D011919:Rats, Inbred Strains; D018709:Statistics, Nonparametric; D000077704:Tirapazamine; D014227:Triazines / Q000494:pharmacology*
D014227:Triazines; D000077704:Tirapazamine