TY - JOUR
T1 - Investigational therapies targeting the androgen signaling axis and the androgen receptor and in prostate cancer–recent developments and future directions
AU - Isaacsson Velho, Pedro
AU - Carducci, Michael A.
N1 - Publisher Copyright:
© 2018, © 2018 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2018/10/3
Y1 - 2018/10/3
N2 - Introduction: Despite the heterogeneity of prostate cancer (PCa), androgen stimulation is fundamental to its development, growth, and lethality. Therefore, the blockade of androgen receptor (AR) signaling is critical to controlling the disease, even after progression with castrate levels of androgens. Areas covered: We review the current understanding of new ways to block the AR, using novel antiandrogen inhibitors, which act on different parts of the AR signaling pathway in PCa. We also review new approaches, such as the use of poly(ADP–ribose) polymerase (PARP) inhibitors, targeting both the AR and the DNA repair pathway, potentially adding synergy and improving efficacy and the combination of AR inhibitors and immunotherapy. Bipolar androgen therapy (BAT), an innovative strategy to target the AR, has shown early evidence of efficacy in PCa is also discussed in detail. We highlight some of the key ongoing studies of greatest relevance to this topic. Expert commentary: Clinical trials investigating new AR-targeted therapies should be encouraged in patients with PCa. While it is unlikely that one AR inhibitor will produce long-lasting responses in a substantial proportion of patients, there is evidence that some strategies, such as the BAT could resensitize the AR to antiandrogens, alternating therapies and delaying time to progression, maximizing benefit to patients.
AB - Introduction: Despite the heterogeneity of prostate cancer (PCa), androgen stimulation is fundamental to its development, growth, and lethality. Therefore, the blockade of androgen receptor (AR) signaling is critical to controlling the disease, even after progression with castrate levels of androgens. Areas covered: We review the current understanding of new ways to block the AR, using novel antiandrogen inhibitors, which act on different parts of the AR signaling pathway in PCa. We also review new approaches, such as the use of poly(ADP–ribose) polymerase (PARP) inhibitors, targeting both the AR and the DNA repair pathway, potentially adding synergy and improving efficacy and the combination of AR inhibitors and immunotherapy. Bipolar androgen therapy (BAT), an innovative strategy to target the AR, has shown early evidence of efficacy in PCa is also discussed in detail. We highlight some of the key ongoing studies of greatest relevance to this topic. Expert commentary: Clinical trials investigating new AR-targeted therapies should be encouraged in patients with PCa. While it is unlikely that one AR inhibitor will produce long-lasting responses in a substantial proportion of patients, there is evidence that some strategies, such as the BAT could resensitize the AR to antiandrogens, alternating therapies and delaying time to progression, maximizing benefit to patients.
KW - Prostate
KW - androgen
KW - cancer
KW - hormone
KW - receptor
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U2 - 10.1080/13543784.2018.1513490
DO - 10.1080/13543784.2018.1513490
M3 - Review article
C2 - 30118330
AN - SCOPUS:85054443612
SN - 1354-3784
VL - 27
SP - 811
EP - 822
JO - Expert Opinion on Investigational Drugs
JF - Expert Opinion on Investigational Drugs
IS - 10
ER -