Resistance to castration is a crucial issue in the treatment of metastatic prostate cancer. Kinase inhibitors (KIs) have been tested as potential alternatives, but none of them are approved yet. KIs are subject of extensive metabolism at both the hepatic and the tumor level. Here, we studied the role of PXR (Pregnane X Receptor), a master regulator of metabolism, in the resistance to KIs in a prostate cancer setting. We confirmed that PXR is expressed in prostate tumors and is more frequently detected in advanced forms of the disease. We showed that stable expression of PXR in 22Rv1 prostate cancer cells conferred a resistance to dasatinib and a higher sensitivity to erlotinib, dabrafenib, and afatinib. Higher sensitivity to afatinib was due to a ~ 2-fold increase in its intracellular accumulation and involved the SLC16A1 transporter as its pharmacological inhibition by BAY-8002 suppressed sensitization of 22Rv1 cells to afatinib and was accompanied with reduced intracellular concentration of the drug. We found that PXR could bind to the promoter and induced its transcription in the presence of PXR agonists. Together, our results suggest that PXR could be a biomarker of response to kinase inhibitors in castration-resistant prostate cancers.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8305337 | PMC |
| http://dx.doi.org/10.3390/cancers13143635 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Here we report results of a phase 1 multi-institutional, open-label, dose-escalation trial (NCT02744287) of BPX-601, an investigational autologous PSCA-directed GoCAR-T® cell product containing an inducible MyD88/CD40 ON-switch responsive to the activating dimerizer rimiducid, in patients with metastatic pancreatic (mPDAC) or castration-resistant prostate cancer (mCRPC). Primary objectives were to evaluate safety and tolerability and determine the recommended phase 2 dose/schedule (RP2D). Secondary objectives included the assessment of efficacy and characterization of the pharmacokinetics of rimiducid.
View Article and Find Full Text PDFBackground: In TALAPRO-2, the poly(ADP-ribose) polymerase inhibitor talazoparib plus the androgen receptor-signaling inhibitor enzalutamide improved radiographic progression-free survival (rPFS) versus placebo plus enzalutamide (hazard ratio [HR] = 0.63; 95% CI, 0.51-0.
View Article and Find Full Text PDFAdvancements in pseudouridine modifying enzyme and cancer.
Front Cell Dev Biol
December 2024
Department of Oncology, The First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, Luoyang, Henan, China.
Pseudouridine (Ψ) is a post-transcriptional modifier of RNA, often referred to as the 'fifth nucleotide' owing to its regulatory role in various biological functions as well as because of its significant involvement in the pathogenesis of human cancer. In recent years, research has revealed various Ψ modifications in different RNA types, including messenger RNA, transfer RNA, ribosomal RNA, small nuclear RNA, and long noncoding RNA. Pseudouridylation can significantly alter RNA structure and thermodynamic stability, as the Ψ-adenine (A) base pair is more stable than the typical uridine (U)-A base pair is due to its structural similarity to adenine.
View Article and Find Full Text PDFSilencing of STEAP3 suppresses cervical cancer cell proliferation and migration via JAK/STAT3 signaling pathway.
Cancer Metab
December 2024
Department of Obstetrics and Gynecology, First Affiliated Hospital, Shihezi University, Shihezi, China.
Article Synopsis
- STEAP3 is a critical protein associated with cervical cancer (CC) progression, showing strong expression in CC tissues and linked to poor patient prognosis.
- The study employed various methods, such as immunohistochemistry and RNA sequencing, to investigate STEAP3's role, revealing that lower methylation levels of STEAP3 are connected to worse outcomes.
- Knockdown of STEAP3 in CC cells reduced their growth and invasion abilities while enhancing drug sensitivity, suggesting STEAP3 drives cancer cell activity through the activation of the JAK/STAT3 signaling pathway.
Clinical assessment of urinary prostate cancer antigen 3 in Chinese population: a large-scale, prospective and multicenter study.
World J Surg Oncol
December 2024
Department of Urology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Background: To assess the clinical utility of PCA3 in the diagnostic accuracy, the correlation between PCA3 and biopsy or pathological characteristics and the performance of PCA3 to reduce the unnecessary biopsies in Chinese population.
Methods: A prospective study including patients with indication of prostate biopsies from 4 centers was conducted. All patients underwent PCA3 urine tests and prostate biopsies.
Want 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!