Stereotactic ablative body radiotherapy (SABR) is currently used as a salvage intervention for men with oligometastatic prostate cancer (PC), and increasingly so since the results of the Stereotactic Ablative Body Radiotherapy for the Comprehensive Treatment of Oligometastatic Cancers (SABR-COMET) trial reported a significant improvement in overall survival with SABR. The addition of androgen deprivation therapy (ADT) to localised prostate radiotherapy improves survival as it sensitises PC to radiotherapy-induced cell death. The importance of the androgen receptor (AR) gene pathway in the development of resistance to radiotherapy is well established. In this review paper, we will examine the data to determine how we can overcome the upregulation of the AR pathway and suggest a strategy for improving outcomes in men with oligometastatic hormone-sensitive PC.
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http://dx.doi.org/10.3390/ijms23094786 | DOI Listing |
Cancers (Basel)
December 2024
Department of Biochemistry and Molecular Biology, LSU Health Shreveport, Shreveport, LA 71103, USA.
For nearly a century, fundamental observations that prostate cancer (PCa) cells nearly always require AR stimulation for sustained proliferation have led to a unidirectional quest to abrogate such a pathway. Similarly focused have been efforts to understand AR-driven processes in the context of elevated expression of its target genes, and much less so on products that become overexpressed when AR signaling is suppressed. Treatment with ARSI results in an increased expression of the TLK1B splice variant via a 'translational' derepression driven by the compensatory mTOR activation and consequent activation of the TLK1 > NEK1 > ATR > Chk1 and NEK1 > YAP axes.
View Article and Find Full Text PDFCancers (Basel)
December 2024
Faculty of Pharmacy, University of Montreal, 2940 Chem. de Polytechnique, Montreal, QC H3T 1J4, Canada.
Background/objectives: Through phase III clinical trials, PARP inhibitors have demonstrated outcome improvements in mCRPC patients with alterations in BRCA1/2 genes who have progressed on a second-generation androgen receptor pathway inhibitor (ARPI). While improving outcomes, PARP inhibitors contribute to the ever-growing economic burden of PCa. The objective of this project is to evaluate the cost-effectiveness of PARP inhibitors (olaparib, rucaparib, or talazoparib) versus the SOC (docetaxel or androgen receptor pathway inhibitors (ARPI)) for previously progressed mCRPC patients with BRCA1/2 mutations from the Canadian healthcare system perspective.
View Article and Find Full Text PDFCancers (Basel)
December 2024
CeRePP, 75020 Paris, France.
Purpose: To identify molecular changes during PCa invasion of adipose space using Spatial Transcriptomic Profiling of PCa cells.
Methods: This study was performed on paired intraprostatic and extraprostatic samples obtained from radical prostatectomy with pT3a pathological stages.
Results: Differential gene expression revealed upregulation of heat shock protein genes: DNAJB1, HSPA8, HSP90AA1, HSPA1B, HSPA1A in PCa PanCK+ cells from the adipose periprostatic space.
Int J Mol Sci
December 2024
Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA.
Prostate cancer (PCa) remains a critical global health challenge, with high mortality rates and significant heterogeneity, particularly in advanced stages. While early-stage PCa is often manageable with conventional treatments, metastatic PCa is notoriously resistant, highlighting an urgent need for precise biomarkers and innovative therapeutic strategies. This review focuses on the dualistic roles of sirtuins, a family of NAD+-dependent histone deacetylases, dissecting their unique contributions to tumor suppression or progression in PCa depending on the cellular context.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Epi Biotech Co., Ltd., Incheon 21983, Republic of Korea.
We previously demonstrated that C-X-C Motif Chemokine Ligand 12 (CXCL12) is primarily secreted by dermal fibroblasts in response to androgens and induces hair miniaturization in the mouse androgenic alopecia (AGA) model. However, the direct effects of androgen-induced CXCL12 on dermal papilla cells (DPCs) and dermal sheath cup cells (DSCs) have not been demonstrated. First, we compared single-cell RNA sequencing data between mouse and human skin, and the results show that CXCL12 is highly co-expressed with the androgen receptor (AR) in the DPCs and DSCs of only human hair.
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