Despite the initial efficacy of androgen deprivation in prostate cancer, virtually all patients progress to castration-resistant prostate cancer (CRPC). Androgen receptor (AR) signaling is critically required for CRPC. A new generation of medications targeting AR, such as abiraterone and enzalutamide, has improved survival of metastatic CRPC (mCRPC) patients. However, a significant proportion of patients presents with primary resistance to these agents, and in the remainder, secondary resistance will invariably develop, which makes mCRPC the lethal form of the disease. Mechanisms underlying progression to mCRPC and treatment resistance are extremely complex. AR-dependent resistance mechanisms include AR amplification, AR point mutations, expression of constitutively active AR splice variants, and altered intratumoral androgen biosynthesis. AR-independent resistance mechanisms include glucocorticoid receptor activation, immune-mediated resistance, and neuroendocrine differentiation. The development of novel agents, such as seviteronel, apalutamide, and EPI-001/EPI-506, as well as the identification and validation of novel predictive biomarkers of resistance, may lead to improved therapeutics for mCRPC patients.
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Cancer Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Δευτέρα 12 Ιουνίου 2017
Cancers, Vol. 9, Pages 67: Androgen Receptor-Dependent and -Independent Mechanisms Involved in Prostate Cancer Therapy Resistance
[Health professionals and cancer prevention in France: The new Danaïdes?]
[Health professionals and cancer prevention in France: The new Danaïdes?]
Bull Cancer. 2017 Jun 07;:
Authors: Braillon A
PMID: 28601191 [PubMed - as supplied by publisher]
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Characterization of VSIG1 exerting a tumor suppressor function in gastric, lung, and esophageal cancer cells
Summary
V-set and immunoglobulin domain containing 1 (VSIG1) is a newly discovered member of the immunoglobulin superfamily proteins, expressed in normal stomach and testis. In cancers, however, the clinical and biological roles of VSIG1 remain unknown. Here we investigated VSIG1 expression in 11 cancers and assessed the prognostic roles of VSIG1 in patients with gastric cancer (GC) (N = 362) and non-small-cell lung cancer (N = 650). VSIG1 was downregulated in 60.5% of GC specimens, and high VSIG1 expression was identified as an independent favorable prognostic factor for overall survival in GC patients (hazard ratio, 0.58; 95% confidence interval, 0.35–0.96). Among lung adenocarcinomas (N = 428), VSIG1 was significantly and inversely associated with thyroid transcription factor 1 (TTF1) expression and was frequently expressed in the invasive mucinous subtype (17 of 19, 89.5%). In addition, VSIG1 was expressed in a subset of pancreatic, ovarian, and prostate cancers. The variant 2 VSIG1 transcript was the dominant form in these tissues and cancer cells. Introduction of VSIG1 significantly reduced the proliferative ability of MKN1 and MKN28 GC cells and H1299 lung cancer cells and downregulated cell migration of these cells, as well as of KYSE150, an esophageal cancer cell line. Cell invasion of MKN1, MKN28, and KYSE150 cells was also reduced by VSIG1 introduction. In vitro characterization revealed that VSIG1 forms homodimers via homophilic cis-interactions but not via homophilic trans-interactions. These results suggest that VSIG1 possesses tumor suppressive functions that are translated into favorable prognosis of VSIG1-expressing GC patients.
This article is protected by copyright. All rights reserved.
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Prognostic value of serum EBV antibodies in patients with nasopharyngeal carcinoma and undetectable pretreatment EBV DNA
Summary
Epstein-Barr virus (EBV) is closely associated with nasopharyngeal carcinoma (NPC). Serum immunoglobulin A (IgA) antibodies against early antigen (EA-IgA) and viral capsid antigen (VCA-IgA) are the most commonly used to screen for NPC in endemic areas. However, the prognostic value of serum EA-IgA and VCA-IgA in patients with NPC were less clear. We hypothesize that serum EA-IgA and VCA-IgA levels have prognostic impact for survival outcomes in NPC patients with undetectable pretreatment EBV (pEBV) DNA. In this series, 334 patients with non-metastatic NPC and undetectable pEBV DNA were included. Serum EA-IgA and VCA-IgA were determined by enzyme-linked immunosorbent assays (ELISA). After analysis, serum EA-IgA and VCA-IgA loads correlated positively with T, N and overall stage (all P < 0.05). Serum EA-IgA was not associated with survival outcomes in univariable analyses. But patients with serum VCA-IgA >1:120 had significantly inferior 5-year progression-free survival (80.4% vs. 89.6%, P=0.025), distant metastasis-free survival (88.4% vs. 94.8%, P=0.050), and locoregional relapse-free survival (88.4% vs. 95.6%, P=0.023; log-rank test). Multivariable analyses revealed that N stage was the only independent prognostic factor (all P < 0.05), but the VCA-IgA became insignificant. Further analyses revealed that serum VCA-IgA was not an independent prognostic factor in early N (N0-1) or advanced N (N2-3) stage NPC. In summary, though both EA-IgA and VCA-IgA correlate strongly with TNM stage, our analyses do not suggest that these antibodies are prognostic biomarkers in patients with NPC and undetectable pEBV DNA.
This article is protected by copyright. All rights reserved.
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Characterization of VSIG1 exerting a tumor suppressor function in gastric, lung, and esophageal cancer cells
Summary
V-set and immunoglobulin domain containing 1 (VSIG1) is a newly discovered member of the immunoglobulin superfamily proteins, expressed in normal stomach and testis. In cancers, however, the clinical and biological roles of VSIG1 remain unknown. Here we investigated VSIG1 expression in 11 cancers and assessed the prognostic roles of VSIG1 in patients with gastric cancer (GC) (N = 362) and non-small-cell lung cancer (N = 650). VSIG1 was downregulated in 60.5% of GC specimens, and high VSIG1 expression was identified as an independent favorable prognostic factor for overall survival in GC patients (hazard ratio, 0.58; 95% confidence interval, 0.35–0.96). Among lung adenocarcinomas (N = 428), VSIG1 was significantly and inversely associated with thyroid transcription factor 1 (TTF1) expression and was frequently expressed in the invasive mucinous subtype (17 of 19, 89.5%). In addition, VSIG1 was expressed in a subset of pancreatic, ovarian, and prostate cancers. The variant 2 VSIG1 transcript was the dominant form in these tissues and cancer cells. Introduction of VSIG1 significantly reduced the proliferative ability of MKN1 and MKN28 GC cells and H1299 lung cancer cells and downregulated cell migration of these cells, as well as of KYSE150, an esophageal cancer cell line. Cell invasion of MKN1, MKN28, and KYSE150 cells was also reduced by VSIG1 introduction. In vitro characterization revealed that VSIG1 forms homodimers via homophilic cis-interactions but not via homophilic trans-interactions. These results suggest that VSIG1 possesses tumor suppressive functions that are translated into favorable prognosis of VSIG1-expressing GC patients.
This article is protected by copyright. All rights reserved.
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Prognostic value of serum EBV antibodies in patients with nasopharyngeal carcinoma and undetectable pretreatment EBV DNA
Summary
Epstein-Barr virus (EBV) is closely associated with nasopharyngeal carcinoma (NPC). Serum immunoglobulin A (IgA) antibodies against early antigen (EA-IgA) and viral capsid antigen (VCA-IgA) are the most commonly used to screen for NPC in endemic areas. However, the prognostic value of serum EA-IgA and VCA-IgA in patients with NPC were less clear. We hypothesize that serum EA-IgA and VCA-IgA levels have prognostic impact for survival outcomes in NPC patients with undetectable pretreatment EBV (pEBV) DNA. In this series, 334 patients with non-metastatic NPC and undetectable pEBV DNA were included. Serum EA-IgA and VCA-IgA were determined by enzyme-linked immunosorbent assays (ELISA). After analysis, serum EA-IgA and VCA-IgA loads correlated positively with T, N and overall stage (all P < 0.05). Serum EA-IgA was not associated with survival outcomes in univariable analyses. But patients with serum VCA-IgA >1:120 had significantly inferior 5-year progression-free survival (80.4% vs. 89.6%, P=0.025), distant metastasis-free survival (88.4% vs. 94.8%, P=0.050), and locoregional relapse-free survival (88.4% vs. 95.6%, P=0.023; log-rank test). Multivariable analyses revealed that N stage was the only independent prognostic factor (all P < 0.05), but the VCA-IgA became insignificant. Further analyses revealed that serum VCA-IgA was not an independent prognostic factor in early N (N0-1) or advanced N (N2-3) stage NPC. In summary, though both EA-IgA and VCA-IgA correlate strongly with TNM stage, our analyses do not suggest that these antibodies are prognostic biomarkers in patients with NPC and undetectable pEBV DNA.
This article is protected by copyright. All rights reserved.
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