ORLANDO, FL, USA (UroToday.com) - Given the frequency of recurrence after treatment for advanced prostate cancer, and the central role of the androgen receptor (AR) in promoting prostate cancer progression, an urgent need exists to develop new methods for targeting AR in both locally advanced and aggressive CRPC.
Knudsen remarked, "The enzyme PARP1 plays a critical role in both DNA repair and regulation of gene expression." At Thomas Jefferson University and the NCI-designated Kimmel Cancer Center, their research of PARP1 inhibitors demonstrated "PARP1 as a means to simultaneously dampen androgen receptor (AR) activity and sensitive prostate cancer cells to genotoxic insult." Additional studies show PARP1 inhibition results in sensitization of both ADT-naive and castration-resistant prostate cancer cells to hormone therapy. The activity of this enyzme also increases as a function of tumor progression (as shown in human models of prostate cancer). By targeting PARP1, the evidence suggests this enzyme not only increases efficacy of castration alone, but it also increase the duration of time to castration resistance.
Dr. Knudsen concluded by saying, "The multiple functions of PARP1 in controlling AR activity and the DNA damage response can be leveraged to improve treatment of advanced prostate cancer (as shown in figure 2)." Ongoing studies are looking at mechanisms that alter PARP1 as a function of disease progression and the identification of which patients would benefit from PARP1 inhibitors.
Highlights of a presentation by Karen E. Knudsen, PhD at the 2013 Genitourinary Cancers Symposium - February 14 - 16, 2013 - Rosen Shingle Creek - Orlando, Florida USA
Thomas Jefferson University, Kimmel Cancer Center, Philadelphia, PA USA
Written by Karen Roberts, medical editor, UroToday.com
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