Docetaxel down‐regulates the expression of androgen receptor and prostate‐specific antigen but not prostate‐specific membrane antigen in prostate cancer cell lines: Implications for PSA surrogacy

Abstract

While DOC did not affect PSMA expression, it was unexpectedly found to down-regulate AR and PSA. DOC-induced down-regulation of AR might be one of the anti-tumor mechanisms active in PC. Down-regulation of PSA may account for the significantly higher PSA response rates (45-50%) relative to measurable response rates (8-17%) reported in DOC PC trials and have implications for PSA surrogacy observations derived from DOC trials.

123I-MIP-1072, a Small-Molecule Inhibitor of Prostate-Specific Membrane Antigen, Is Effective at Monitoring Tumor Response to Taxane Therapy

“…Several reports have indicated that PSMA expression, as opposed to other prostate-specific markers, is unchanged after taxane therapy in humans (32,33). For example, Kuroda et al found that androgen receptor and PSA levels were downregulated in a dose-dependent manner in response to docetaxel (33), possibly accounting for the higher PSA response rates (45%-50%) relative to the measurable response rates (8%-17%) in the 2 phase III trials that led the Food and Drug Administration to approve docetaxel in the treatment of prostate cancer (25,26). These findings further suggest that a molecular imaging radiopharmaceutical targeting PSMA would provide a better gauge of therapeutic responses than monitoring patient response through serum PSA levels or other suboptimal imaging modalities.…”

PSA-based treatment response criteria in castration-resistant prostate cancer: promises and limitations

“…In fact, the use of PSA as a marker of response in docetaxel-treated CRPC has several limitations. First, in vitro, docetaxel has been shown to down-regulate androgen receptor expression and PSA expression/secretion, 8 which could explain the discrepancy commonly seen in clinical trials between the rate of PSA and measurable disease responses. 1,2 Second, CRPC is a heterogeneous disease (intra-and inter-individually) with respect to PSA expression and to chemosensitivity.…”

New Paradigms in Microtubule-Mediated Endocrine Signaling in Prostate Cancer

“…Kuroda and colleagues recently showed downregulation of androgen receptor and PSA expression in different prostate cancer cell lines following exposure to docetaxel in vitro (27). Conversely, overexpression of androgen receptor in prostate cancer cells resulted in partial abrogation of cytotoxic effects of docetaxel (27). Thus, docetaxel mediates inhibitory effects on the expression of androgen receptors and PSA (Fig.…”

“…Figure 1 is a schematic illustration of some of the emerging mechanistic scenarios of the effects of taxanes on microtubules and androgen receptor signaling in prostate cancer. Kuroda and colleagues recently showed downregulation of androgen receptor and PSA expression in different prostate cancer cell lines following exposure to docetaxel in vitro (27). Conversely, overexpression of androgen receptor in prostate cancer cells resulted in partial abrogation of cytotoxic effects of docetaxel (27).…”