Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Progression of prostate cancer following castration is associated with increased androgen receptor (AR) expression and signaling despite AR blockade. Recent studies suggest that these activities are due to the generation of constitutively active AR splice variants, but the mechanisms by which these splice variants could mediate such effects are not fully understood. Here we have identified what we believe to be a novel human AR splice variant in which exons 5, 6, and 7 are deleted (ARv567es) and demonstrated that this variant can contribute to cancer progression in human prostate cancer xenograft models in mice following castration. We determined that, in human prostate cancer cell lines, ARv567es functioned as a constitutively active receptor, increased expression of full-length AR (ARfl), and enhanced the transcriptional activity of AR. In human xenografts, human prostate cancer cells transfected with ARv567es cDNA formed tumors that were resistant to castration. Furthermore, the ratio of ARv567es to ARfl expression within the xenografts positively correlated with resistance to castration. Importantly, we also detected ARv567es frequently in human prostate cancer metastases. In summary, these data indicate that constitutively active AR splice variants can contribute to the development of castration-resistant prostate cancers and may serve as biomarkers for patients who are likely to suffer from early recurrence and are candidates for therapies directly targeting the AR rather than ligand.
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PMID:Castration resistance in human prostate cancer is conferred by a frequently occurring androgen receptor splice variant. 2111 89

Progression of prostate cancer and prostate-specific antigen (PSA) elevation are closely associated. In fewer than 1% of all cases, disease progression may occur despite low or undetectable PSA levels. In these conditions, androgen deprivation therapy is relatively ineffective, and the prostate cancer progresses very quickly. We present a 65-year-old man with non-PSA-secreting prostate cancer and widespread metastases with rather fair response to Lu-prostate-specific membrane antigen radioligand therapy.
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PMID:Radioligand Therapy With 177Lu-Prostate-Specific Membrane Antigen in a Patient With Non-Prostate-Specific Antigen-Secreting Metastatic Prostate Cancer. 3270 8