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worldwide may be a useful addition to better define the
options for enzalutamide and darolutamide therapy in
prostate cancer
[8]. Individualization of treatment and the
timing and duration of therapy are issues of considerable
interest.
Personalized medicine approaches are clearly a focus
of interest in urological oncology. More complete
knowledge of the expression of AR mutants may be
necessary for better selection of patients who will benefit
from therapy. It seems that screening of a larger number
of tumor metastases may be necessary to properly
identify these patients. Heterogeneity among prostate
cancer metastases may be a limiting factor in such
attempts. However, progress with biobanking, including
sampling of specimens from patients with castration-
resistant prostate cancer, has been achieved and appro-
priate strategies have been extended to most urological
centers. The issues mentioned in the commentary are
challenges for the future. In summary, the article by
Borgmann and associates
[1]is one of the first attempts to
overcome enzalutamide resistance in various preclinical
models with multiple AR mutations and is certainly an
important factor for consideration in clinical trials in the
future.
Conflicts of interest:
The author has nothing to disclose.
References
[1]
Borgmann H, Lallous N, Ozistanbullu D, et al. Moving towards precision urologic oncology: targeting enzalutamide-resistant prostate cancer and mutated forms of the androgen receptor using the novel inhibitor darolutamide (ODM-201). Eur Urol 2018;73:4 – 8.
[2]
Paul N, Carabet LA, Lallous N, et al. Cheminformatics modeling of adverse drug responses by clinically relevant mutants of human androgen receptor. J Chem Inf Model 2016;56:2507 – 16.
[3]
Joseph JD, Lu N, Qian J, et al. A clinically relevant androgen receptor mutation confers resistance to second-generation antiandrogens enzalutamide and ARN-509. Cancer Discov 2013;3:1020 – 9.
[4]
Puhr M, Hoefer J, Schäfer G, et al. Epithelial to mesenchymal transition leads to docetaxel resistance in prostate cancer and is mediated by reduced expression of miR-200c and miR-205. Am J Pathol 2012;181:2188 – 201.
[5]
Sun Y, Wang BE, Leong KE, et al. Androgen deprivation causes epithelial mesenchymal transition in the prostate: implications for androgen-deprivation therapy. Cancer Res 2012;72:527 – 36.
[6]
Montanari M, Rosetti S, Cavaliere C, et al. Epithelial mesenchymal transition in prostate cancer: an overview. Oncotarget 2017; 8:35376 – 89.
[7]
Qin J, Lee HJ, Wu SP, et al. Androgen deprivation-induced NCoA2 promotes metastatic and castration-resistant prostate cancer. J Clin Invest 2014;124:5013 – 26.
[8]
Hoefer J, Akbor M, Handle F, et al. Critical role of androgen receptor level in prostate cancer cell resistance to new generation antian- drogen enzalutamide. Oncotarget 2016;7:59781 – 94.
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