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Biologic agents as adjunctive therapy for prostate cancer: a rationale for use with androgen deprivation

Nature Clinical Practice Urology volume 4, pages 82–94 (2007)Cite this article

Abstract

The prevalence of prostate cancer emphasizes the need for improved therapeutic options, particularly for metastatic disease. Current treatment includes medical or surgical castration, which initially induces apoptosis of prostate cancer cells, but ultimately an androgen-independent subpopulation emerges. In addition to a transient therapeutic effect, androgen-deprivation therapy (ADT) can initiate biochemical events that may contribute to the development of and progression to an androgen-independent state. This transition involves multiple signal transduction pathways that are accompanied by many biochemical changes resulting from ADT. These molecular events themselves are therapeutic targets and serve as a rationale for adjunctive treatment at the time of ADT.

Key Points

  • Although not completely understood, the progression of prostate cancer to an androgen-independent state probably involves multiple biochemical pathways

  • Therapeutic androgen ablation is likely to be an initial factor driving this biochemical cascade of events

  • Novel biologic agents are now available enabling modification of some of the pathways involved in the development of androgen-independent prostate cancer

  • Current clinical data shows some efficacy for biologic agents when used with chemotherapy in the setting of androgen-independent disease

  • Future trials should also test biologic agents at the time of androgen ablation to attempt to maximize the initial apoptotic response and delay the onset of androgen independence

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Figure 1: Three possible pathways leading to androgen-independent prostate cancer.
Figure 2: Comparison of growth factor and neuropeptide signaling pathways emphasizing cross-talk between them.

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Acknowledgements

Research supported in part by NIH grant KO8 DK60748-01 and Department of Defense grant PC040161.

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Authors and Affiliations

  1. PN Lara Jr is Professor of Medical Oncology and CP Evans is Associate Professor and Chair of the Urology Department, EC Nelson is a Urology Research Fellow, JC Yang is an Assistant Research Biologist, University of California, Davis, CA.,

    Eric C Nelson, Joy C Yang, Primo N Lara Jr & Christopher P Evans

  2. AJ Cambio is a Urology Resident at the University of Rochester, Rochester, NY, USA.,

    Angelo J Cambio

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Correspondence to Christopher P Evans.

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Nelson, E., Cambio, A., Yang, J. et al. Biologic agents as adjunctive therapy for prostate cancer: a rationale for use with androgen deprivation. Nat Rev Urol 4, 82–94 (2007). https://doi.org/10.1038/ncpuro0700

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