Taxanes are the only chemotherapies used to treat patients with metastatic castration-resistant prostate cancer (CRPC). Despite the initial efficacy of taxanes in treating CRPC, all patients ultimately fail due to the development of drug resistance. In this study, we show that ERG overexpression in in vitro and in vivo models of CRPC is associated with decreased sensitivity to taxanes. ERG affects several parameters of microtubule dynamics and inhibits effective drug-target engagement of docetaxel or cabazitaxel with tubulin. Finally, analysis of a cohort of 34 men with metastatic CRPC treated with docetaxel chemotherapy reveals that ERG-overexpressing prostate cancers have twice the chance of docetaxel resistance than ERG-negative cancers. Our data suggest that ERG plays a role beyond regulating gene expression and functions outside the nucleus to cooperate with tubulin towards taxane insensitivity. Determining ERG rearrangement status may aid in patient selection for docetaxel or cabazitaxel therapy and/or influence co-targeting approaches.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4244604 | PMC |
| http://dx.doi.org/10.1038/ncomms6548 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Alkaline phosphatase decline and pain response as predictors of overall survival benefit in patients treated with radium-223: a post hoc analysis of the REASSURE study.
Br J Cancer
January 2025
Mayo Clinic, Rochester, MN, USA.
Background: Alkaline phosphatase (ALP) declines and pain responses can occur during radium-223 (Ra) treatment, but their association with treatment outcomes is unclear.
Methods: For patients with metastatic castration-resistant prostate cancer treated with Ra in the REASSURE study, we investigated whether ALP decline (Week 12) and/or pain response (during treatment) are associated with improved overall survival (OS). The Brief Pain Inventory-Short Form (BPI-SF) was used to assess pain at baseline and pain response (in patients with baseline BPI-SF score ≥2).
Cynanchum wallichii Wight and CW1 reversed docetaxel resistance effects by inhibiting P-gp and promoting PI3K/Akt-mediated apoptosis in prostate cancer.
Biochem Pharmacol
January 2025
Guangdong Provincial Key Laboratory of Translational Cancer Research of Chinese Medicines, Joint International Research Laboratory of Translational Cancer Research of Chinese Medicines, International Institute for Translational Chinese Medicine, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China. Electronic address:
Cynanchum wallichii (CW) is a traditional Chinese medicine which is widely used for treating arthrophlogosis, traumatic injury, and other conditions. Herein, we investigate the effects and mechanisms of CW and its bioactive constituent CW1 in reversing docetaxel (DTX) resistance in prostate cancer (PCa) cells. We investigated the reversal effects of CW and its bioactive constituent CW1 on 22Rv1/DTX cells in vitro and in vivo.
View Article and Find Full Text PDFGermline and Somatic Genomic Testing for Metastatic Prostate Cancer: ASCO Guideline.
J Clin Oncol
January 2025
Jefferson Einstein Medical Center, Sidney Kimmel Cancer Center of Thomas Jefferson University, Philadelphia, PA.
Purpose: To evaluate evidence on germline and somatic genomic testing for patients with metastatic prostate cancer and provide recommendations.
Methods: A systematic review by a multidisciplinary panel with patient representation was conducted. The PubMed database was searched from January 2018 to May 2024.
NXP800 activates the unfolded protein response, altering AR and E2F function to impact castration-resistant prostate cancer growth.
Clin Cancer Res
January 2025
Institute of Cancer Research, Sutton, Surrey, United Kingdom.
Purpose: Advanced prostate cancer (PCa) is invariably fatal with the androgen receptor (AR) being a major therapeutic target. AR signaling inhibitors have improved overall survival for men with advanced PCa, but treatment resistance is inevitable and includes reactivation of AR signaling. Novel therapeutic approaches targeting these mechanisms to block tumor growth is an urgent unmet clinical need.
View Article and Find Full Text PDFPrimary Cilia Formation Mediated by Hsa_Circ_0005185/OTUB1/RAB8A Complex Inhibits Prostate Cancer Progression by Suppressing Hedgehog Signaling Pathway.
Adv Sci (Weinh)
January 2025
Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, 200030, China.
Prostate cancer (PCa) is one of the most common malignancies for male individuals globally. Androgen deprivation therapy (ADT) initially demonstrated significant efficacy in treating PCa; however, most cases of PCa eventually progress to castration-resistant prostate cancer (CRPC), which becomes increasingly challenging to manage. Notably, the loss or disruption of primary cilia in PCa cells may play a critical role in the progression of the disease, and there are no reports on the role of circular RNAs in ciliogenesis.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!