Does Hypoxia Contribute to the Failure of Androgen Ablation Therapy in Prostate Cancer?

来源 :BIT‘s2nd Annual World Cancer Congess-2009 (2009第二届癌症大会) | 被引量 : 0次 | 上传用户:mylifefover12
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  Tumour hypoxia is an important prognostic indicator for poor prognosis in many tumour types including those arising in the prostate.There is now considerable evidence indicating that hypoxia selects for cells which have stress-resistant / more malignant characteristics.Previously we have developed a drug, banoxantrone (AQ4N) which targets these hypoxic treatment-resistant cells through a bioreductive mechanism.We have now investigated the potential for this drug to be combined with androgen ablation therapy (AAT).The rationale for this approach is the observation that androgen dependent prostate tumours, in patients who are treated with AAT, frequently progress within 1.5-2 years, to an androgen independent phenotype which is very difficult to treat.The underlying mechanisms which cause this are poorly understood but may include stress factors exerted by the tumour microenvironment during exposure to AAT.Several reports have shown that withdrawal of hormones via castration results in reduction of the prostate associated vasculature, probably resulting in widespread tissue hypoxia.
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