scholarly journals Targeting CDC25C, PLK1 and CHEK1 to overcome Docetaxel resistance induced by loss of LZTS1 in prostate cancer

Oncotarget ◽  
2014 ◽  
Vol 5 (3) ◽  
pp. 667-678 ◽  
Author(s):  
Nader Al Nakouzi ◽  
Sophie Cotteret ◽  
Frédéric Commo ◽  
Catherine Gaudin ◽  
Shanna Rajpar ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Docetaxel Resistance

MP24-06 INTERACTION BETWEEN DOCETAXEL RESISTANCE AND CASTRATION RESISTANCE IN PROSTATE CANCER: IMPLICATIONS OF TWIST1, YB-1 AND ANDROGEN RECEPTOR

2014 ◽  
Vol 191 (4S) ◽  
Author(s):  
Masaki Shiota ◽  
Eiji Kashiwagi ◽  
Akira Yokomizo ◽  
Ario Takeuchi ◽  
Takeshi Dejima ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Castration Resistance ◽  
Docetaxel Resistance

scholarly journals Glucocorticoid receptor antagonism reverts docetaxel resistance in human prostate cancer

2015 ◽  
Vol 23 (1) ◽  
pp. 35-45 ◽  
Author(s):  
Jan Kroon ◽  
Martin Puhr ◽  
Jeroen T Buijs ◽  
Geertje van der Horst ◽  
Daniëlle M Hemmer ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Glucocorticoid Receptor ◽  
Cell Lines ◽  
Chemotherapy Resistance ◽  
Clinical Problem ◽  
Dependent Manner ◽  
Ru 486 ◽  
Docetaxel Resistance ◽  
Docetaxel Treatment

Resistance to docetaxel is a major clinical problem in advanced prostate cancer (PCa). Although glucocorticoids (GCs) are frequently used in combination with docetaxel, it is unclear to what extent GCs and their receptor, the glucocorticoid receptor (GR), contribute to the chemotherapy resistance. In this study, we aim to elucidate the role of the GR in docetaxel-resistant PCa in order to improve the current PCa therapies. GR expression was analyzed in a tissue microarray of primary PCa specimens from chemonaive and docetaxel-treated patients, and in cultured PCa cell lines with an acquired docetaxel resistance (PC3-DR, DU145-DR, and 22Rv1-DR). We found a robust overexpression of the GR in primary PCa from docetaxel-treated patients and enhanced GR levels in cultured docetaxel-resistant human PCa cells, indicating a key role of the GR in docetaxel resistance. The capability of the GR antagonists (RU-486 and cyproterone acetate) to revert docetaxel resistance was investigated and revealed significant resensitization of docetaxel-resistant PCa cells for docetaxel treatment in a dose- and time-dependent manner, in which a complete restoration of docetaxel sensitivity was achieved in both androgen receptor (AR)-negative and AR-positive cell lines. Mechanistically, we demonstrated down-regulation of Bcl-xL and Bcl-2 upon GR antagonism, thereby defining potential treatment targets. In conclusion, we describe the involvement of the GR in the acquisition of docetaxel resistance in human PCa. Therapeutic targeting of the GR effectively resensitizes docetaxel-resistant PCa cells. These findings warrant further investigation of the clinical utility of the GR antagonists in the management of patients with advanced and docetaxel-resistant PCa.

Activated Wnt/β-Catenin signaling contributes to E3 ubiquitin ligase EDD-conferred docetaxel resistance in prostate cancer

Life Sciences ◽  
2020 ◽  
Vol 254 ◽  
pp. 116816
Author(s):  
Pan Bian ◽  
Zhongling Dou ◽  
Zhaohui Jia ◽  
Wensheng Li ◽  
Dong Pan
Keyword(s):  
Prostate Cancer ◽  
Ubiquitin Ligase ◽  
E3 Ubiquitin Ligase ◽  
Docetaxel Resistance

scholarly journals Increased ABCC4 Expression Induced by ERRα Leads to Docetaxel Resistance via Efflux of Docetaxel in Prostate Cancer

2020 ◽  
Vol 10 ◽  
Author(s):  
Houbao Huang ◽  
Jing Li ◽  
Jing Shen ◽  
Ling Lin ◽  
Xu Wu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Docetaxel Resistance

βIII-tubulin expression as a predictor of docetaxel resistance in metastatic castrate-resistant prostate cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15174-e15174
Author(s):  
Bertha E. Sanchez ◽  
Nilesh Gupta ◽  
Meredith Mahan ◽  
Evelyn R Barrack ◽  
Prem-veer Reddy ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Gleason Score ◽  
Clinical Decision Making ◽  
Performance Status ◽  
Ecog Performance Status ◽  
Docetaxel Resistance ◽  
Psa Response ◽  
Castrate Resistant Prostate Cancer ◽  
The Mean ◽  
Castrate Resistant

e15174 Background: Docetaxel is a tubulin-targeting cytotoxic that remains first-line therapy in metastatic castrate-resistant prostate cancer (mCRPC) patients (pts) even though half of pts are reported to be non-responders. A predictive marker to identify those who will benefit from docetaxel-therapy will assist clinical decision making. High βIII-tubulin (TUBB3) expression has previously been reported to correlate with lack of response to taxanes in other cancers. We evaluated TUBB3 expression as a predictor of docetaxel-resistance in mCRPC. Methods: mCRPC pts treated with at least 3 cycles of docetaxel between 1990 and 2011 were identified retrospectively. TUBB3 immunostaining was performed on archival formalin-fixed, paraffin-embedded tissue. Stain intensity was scored from 0 to 3; 2 and 3 were interpreted as positive. Rates of PSA response were compared between pts with positive (+) and negative (-) TUBB3 expression. Two definitions of PSA response were evaluated (any PSA decline and at least 50% decline). Overall survival (OS) distribution between TUBB3+ and TUBB3- pts was estimated by the Kaplan-Meier method. Results: Of 73 pts, 26 (35%) expressed TUBB3. At diagnosis, the mean age was 65.7 years and the median Gleason score was 8. At the time of docetaxel therapy, the mean age was 71.2 years, the median PSA level was 70.9 (range, 0.2-5253) and 76% had ECOG performance status ≤1. The median number of docetaxel cycles was 7 (range, 3-18). The total dose of docetaxel was not different between groups (p=0.705). The median OS was 19.2 mo. TUBB3 expression was not correlated with any clinical or pathological characteristic (age, Gleason score, stage, ECOG, PSA, LDH, alkaline phosphatase, hemoglobin, visceral disease or chemotherapy before docetaxel). 65% of TUBB3+ pts had any PSA decline compared to 89% of pts with TUBB3- (p=0.0267). 52% of TUBB3+ pts had a PSA decline of ≥ 50% compared to 70% of TUBB3- pts (p=0.0144). Median OS for TUBB3+ pts was 16.8 mo compared to 20.4 mo in TUBB3- pts (p=0.039). Conclusions: High TUBB3 expression was associated with shorter OS and lower PSA response rates in mCRPC pts treated with docetaxel. These findings need to be validated prospectively.

EGFR mediates docetaxel resistance in human castration-resistant prostate cancer through the Akt-dependent expression of ABCB1 (MDR1)

2014 ◽  
Vol 89 (4) ◽  
pp. 591-605 ◽  
Author(s):  
Tzyh-Chyuan Hour ◽  
Shiu-Dong Chung ◽  
Wang-Yi Kang ◽  
Ying-Chu Lin ◽  
Shu-Ju Chuang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Castration Resistant Prostate Cancer ◽  
Docetaxel Resistance ◽  
Castration Resistant

Evaluation of Docetaxel-Sensitive and Docetaxel-Resistant Proteomes in PC-3 Cells

2015 ◽  
Vol 95 (1) ◽  
pp. 114-119 ◽  
Author(s):  
Shulu Zu ◽  
Weiming Ma ◽  
Pan Xiao ◽  
Yazhou Cui ◽  
Tianjia Ma ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Molecular Mechanisms ◽  
Polyacrylamide Gel Electrophoresis ◽  
Acquired Resistance ◽  
Castration Resistant Prostate Cancer ◽  
Ionization Time ◽  
Flight Mass Spectrometry ◽  
Docetaxel Resistance ◽  
Castration Resistant ◽  
Glucose Regulated Protein

Objectives: Docetaxel was the first drug with proven survival benefit in men with castration-resistant prostate cancer. Acquired resistance to docetaxel precedes fatality in castration-resistant prostate cancer. The aims of this study were to evaluate docetaxel-sensitive and docetaxel-resistant proteomes in PC-3 cells, and to investigate the molecular mechanism of docetaxel-resistant PC-3 cells. Methods: Docetaxel-resistant PC-3 cells were developed by docetaxel dose escalation. The global profiling of the protein expression was investigated in docetaxel-sensitive and docetaxel-resistant proteomes in PC-3 cells using 2-dimensional polyacrylamide gel electrophoresis/matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Results: Forty-nine differential proteins were found in docetaxel-resistant PC-3 cells in comparison with docetaxel-sensitive PC-3 cells. Expression in 29 proteins was upregulated, whereas expression in 20 proteins was downregulated. ATP synthase and galectin-1 were involved in the formation of tumor vessels; calreticulin, cathepsin D, and cofilin were involved in tumor metastasis, and GRP78 (78-kDa glucose-regulated protein) and microtubule-associated protein-6 were involved in drug resistance of tumor. Conclusion: It is suggested that a proteomic expression difference exists between docetaxel-sensitive and docetaxel-resistant PC-3 cells, which would be helpful for further understanding the molecular mechanisms of docetaxel resistance in PC-3 cells.

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