Prostate Cancer: Molecular Mechanism Of The Supra- Additive Response To Androgen Ablation And Radiotherapy

Life Sciences & Biotechnology Update, Feb, 2001

The main objectives of this (M.D. Anderson Cancer Center) project are to: measure the molecular changes induced by androgen ablation and radiotherapy; relate these changes to the supra-additive apoptotic response of androgen ablation plus radiation; use these data to develop a gene therapy strategy. Prostate cancer is the most common cancer in men, yet our understanding of the interaction of androgen ablation and radiation at the molecular level is severely lacking. The project defines the role of the key proteins in the apoptotic pathway: p53; bax; and bcl-2. Considerable progress is reported on two fronts: (1) characterization of pretreatment biomarker levels in human prostate cancers; and (2) development of a gene therapy strategy using adenoviral-p53 and adenoviral-E2F. In the latter studies, these vectors sensitize both LNCaP and PC3 cells to radiation, and preliminary data with Ad5-p53 suggest an added benefit when androgen ablation is added.

Some delays have been encountered in measurement of biomarker level changes in LNCaP cells cultured in androgen-deprived medium. The problems with the system have been resolved and this analysis is now underway. The immediate significance of these studies is that two gene therapy strategies have been developed, and a clinical trial has been written to test the feasibility, morbidity, and efficacy of this approach. The significance of the androgen ablation mechanism/biomarker studies will be manifest at the end of next year.

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