Development and prevalence of castration-resistant prostate cancer subtypes

Castration-resistant prostate cancer (CRPC) occurs when prostate cancer (CaP) progresses under therapy-induced castrate conditions. Several mechanisms have been proposed to explain this acquired resistance, many of which are driven by androgen receptor (AR). Recent findings, however, sub-classified...

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Vydáno v:Neoplasia (New York, N.Y.) Ročník 22; číslo 11; s. 566 - 575
Hlavní autoři: Vellky, Jordan E., Ricke, William A.
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States Elsevier Inc 01.11.2020
Neoplasia Press
Elsevier
Témata:
AR low prostate cancer
Castration-resistant prostate cancer
Double negative prostate cancer
Neuroendocrine prostate cancer
Review article
Therapy resistance
NEPC
Castration-resistant prostate cancer
ADT
AR
AR low prostate cancer
Neuroendocrine prostate cancer
CaP
Therapy resistance
ARLPC
ARSI
Double negative prostate cancer
CRPC
DNPC
ISSN:1476-5586, 1522-8002, 1476-5586
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Shrnutí:Castration-resistant prostate cancer (CRPC) occurs when prostate cancer (CaP) progresses under therapy-induced castrate conditions. Several mechanisms have been proposed to explain this acquired resistance, many of which are driven by androgen receptor (AR). Recent findings, however, sub-classified CRPC by downregulation/absence of AR in certain subtypes that consequently do not respond to anti-androgen therapies. To highlight the significance of CRPC sub-classification, we reviewed the development and treatment of CRPC, AR downregulation in CRPC, and summarized recent reports on the prevalence of CRPC subtypes. Using a medline-based literature search, we reviewed mechanisms of CRPC development, current treatment schemes, and assessed the prevalence of AR low/negative subtypes of CRPC. Additionally, we performed immunohistochemical staining on human CRPC specimens to quantify AR expression across CRPC subtypes. In the majority of cases, CRPC continues to rely on AR signaling, which can be augmented in castrate-conditions through a variety of mechanisms. However, recently low/negative AR expression patterns were identified in a significant proportion of patient samples from a multitude of independent studies. In these AR low/negative cases, we postulated that AR protein may be downregulated by (1) promoter methylation, (2) transcriptional regulation, (3) post-transcriptional regulation by microRNA or RNA-binding-proteins, or (4) post-translational ubiquitination-mediated degradation. Here, we discussed mechanisms of CRPC development and summarized the overall prevalence of CRPC subtypes; interestingly, AR low/negative CRPC represented a considerable proportion of diagnoses. Because these subtypes cannot be effectively treated with AR-targeted therapeutics, a better understanding of AR low/negative subtypes could lead to better treatment strategies and increased survival.
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ISSN:1476-5586
1522-8002
1476-5586
DOI:10.1016/j.neo.2020.09.002