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About half of the 473 active human proteases are expressed in the prostate and many of the most well\u2010characterized members of this enzyme family are regulated by androgens, hormones essential for development of prostate cancer. Most notably, several kallikrein\u2010related peptidases, including KLK3 (prostate\u2010specific antigen, PSA), the most well\u2010known prostate cancer marker, and type II transmembrane serine proteases, such as TMPRSS2 and matriptase, have been extensively studied and found to promote prostate cancer progression. Recent findings also suggest a critical role for proteases in the development of advanced and aggressive castration\u2010resistant prostate cancer (CRPC). Perhaps the most intriguing evidence for this role comes from studies showing that the protease\u2010activated transmembrane proteins, Notch and CDCP1, are associated with the development of CRPC. 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