Research ArticleCancer

Targeting Poly(ADP-Ribose) Polymerase and the c-Myb–Regulated DNA Damage Response Pathway in Castration-Resistant Prostate Cancer

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Science Signaling  20 May 2014:
Vol. 7, Issue 326, pp. ra47
DOI: 10.1126/scisignal.2005070

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Improving Therapy in Prostate Cancer

Blocking androgen receptor (AR) signaling is standard therapy for prostate cancer, but tumor growth often recurs. Li et al. examined the gene expression profile in patient samples of primary and metastatic prostate cancer from patients in which AR signaling was blocked. Metastatic disease, which is associated with androgen inhibitor–resistant relapse, correlated with increased expression of genes encoding proteins in the DNA damage response (DDR) and MYB expression. AR and c-Myb shared a subset of target genes that encode DDR proteins; thus, c-Myb may functionally substitute for AR in the regulation of their common DDR targets. Targeting proteins within the Myb-regulated network in combination with a poly[adenosine 5′-diphosphate (ADP)–ribose] polymerase (PARP) inhibitor, which compromises the DDR, generated synergistic lethality in prostate cancer cells in culture and in mouse xenografts, suggesting potential new options for prostate cancer patients.

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