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Biological Impact of Senescence Induction in Prostate Cancer Therapy

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Annual rept. 15 Dec 2007-14 Dec 2008

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Recently, it has been recognized that a distinct mechanism of terminal proliferation arrest after chemotherapy involves the reactivation of senescence. However, whether this phenotype occurs in vivo is unclear, as is the biological impact of senescence induction. We have previously identified pathways and genes involved in human senescence that may serve as senescence markers, and have demonstrated that senescence occurs in prostate cancer cell lines after chemotherapy. In this proposal, we will a determine whether senescent tumor cells alter the proliferation and invasion of surrounding prostate cancer cells in vitro and in vivo, b assess for and augment senescence in prostate cancer xenograft models and human tumors, and c identify novel small molecules that induce senescence in prostate cancer cells. Both in vitro and in vivo approaches using human prostate cancer cells will be utilized to identify and determine the mechanisms underlying senescence. With this data, our understanding of cellular senescence will undergo a quantum leap and permit the translation of this entity both as a marker of response and for directing therapy.

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  • Biochemistry
  • Anatomy and Physiology
  • Medicine and Medical Research

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