TY - JOUR
T1 - Understanding and overcoming the mechanisms of primary and acquired resistance to abiraterone and enzalutamide in castration resistant prostate cancer
AU - Buttigliero, Consuelo
AU - Tucci, Marcello
AU - Bertaglia, Valentina
AU - Vignani, Francesca
AU - Bironzo, Paolo
AU - Di Maio, Massimo
AU - Scagliotti, Giorgio Vittorio
PY - 2015
Y1 - 2015
N2 - In recent years, in castration resistant prostate cancer (CRPC), several new drugs have been approved that prolong overall survival, including enzalutamide and abiraterone, two new-generation hormonal therapies. Despite the demonstrated benefit of these agents, not all patients with CRPC are responsive to treatment, the gain in median progression-free survival with these therapies compared to standard of care is, rather disappointingly, still less than six months and the appearance of acquired resistance is almost universal. Approximately one third of patients treated with abiraterone and 25% of those treated with enzalutamide show primary resistance to these agents. Even if the mechanisms of resistance to these agents are not fully defined, many hypotheses are emerging, including systemic and intratumoral androgen biosynthesis up-regulation, androgen receptor (AR) gene mutations and amplifications, alteration of pathways involved in cross-talk with AR signaling, glucocorticoid receptor overexpression, neuroendocrine differentiation, immune system deregulation and others. The aim of this paper is to review currently available data about mechanisms of resistance to abiraterone and enzalutamide, and to discuss how these mechanisms could be potentially overcome through novel therapeutic agents.
AB - In recent years, in castration resistant prostate cancer (CRPC), several new drugs have been approved that prolong overall survival, including enzalutamide and abiraterone, two new-generation hormonal therapies. Despite the demonstrated benefit of these agents, not all patients with CRPC are responsive to treatment, the gain in median progression-free survival with these therapies compared to standard of care is, rather disappointingly, still less than six months and the appearance of acquired resistance is almost universal. Approximately one third of patients treated with abiraterone and 25% of those treated with enzalutamide show primary resistance to these agents. Even if the mechanisms of resistance to these agents are not fully defined, many hypotheses are emerging, including systemic and intratumoral androgen biosynthesis up-regulation, androgen receptor (AR) gene mutations and amplifications, alteration of pathways involved in cross-talk with AR signaling, glucocorticoid receptor overexpression, neuroendocrine differentiation, immune system deregulation and others. The aim of this paper is to review currently available data about mechanisms of resistance to abiraterone and enzalutamide, and to discuss how these mechanisms could be potentially overcome through novel therapeutic agents.
KW - Abiraterone
KW - Enzalutamide
KW - Mechanisms of resistance
KW - Prostate cancer
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U2 - 10.1016/j.ctrv.2015.08.002
DO - 10.1016/j.ctrv.2015.08.002
M3 - Article
C2 - 26342718
AN - SCOPUS:84958937320
VL - 41
SP - 884
EP - 892
JO - Cancer Treatment Reviews
JF - Cancer Treatment Reviews
SN - 0305-7372
IS - 10
ER -